Carbon Chemist

Tag: Placebo

  • Can postbiotics improve athletic performance and recovery?

    Can postbiotics improve athletic performance and recovery?

    [ad_1]

    A recent systematic review published in Nutrients describes the utility of postbiotics in improving exercise performance and recovery.

    Study: It’s Dead! Can Postbiotics Really Help Performance and Recovery? A Systematic Review. Image Credit: Doucefleur / Shutterstock.com

    Probiotics vs. postbiotics

    Probiotics are live microorganisms that are associated with a wide variety of health benefits to the host when administered adequately. For example, probiotics can support gut health, improve mental health, prevent cardiometabolic diseases, improve sleep quality and duration, as well as reduce allergic reactions. Probiotics exert these health benefits through their effects on the immune system by reducing intestinal pH, maintaining intestinal barrier integrity, increasing gut microbial composition and diversity, reducing inflammation, and eliminating pathogens.

    Recently, the International Society of Sports and Nutrition has stated that probiotics might be beneficial for improving exercise performance and recovery, in addition to supporting the training and competition demands of athletes.

    In addition to probiotics, postbiotics have recently gained considerable attention in healthcare due to their potential ability to improve health. A significant advantage of using postbiotics for health purposes is their longer shelf-life and reduced susceptibility to degradation due to changes in ambient conditions.

    According to the International Scientific Association of Probiotics and Prebiotics (ISAPP), a postbiotic is defined as a preparation of inanimate microorganisms and/or their components that confers health benefits. Existing evidence indicates that postbiotics can exert positive health effects on gastrointestinal, dermatological, and respiratory diseases.

    Some of the different methods used to produce postbiotic preparations from live microorganisms include heat treatment, sonification, chemical treatment, and ultraviolet (UV) irradiation. Each method, as well as the processing condition, has a differential impact on the functionality of resulting postbiotics.

    About the study

    The authors systematically searched various electronic databases to identify studies that investigated the impact of postbiotic supplementation, specifically on exercise performance, recovery, as well as biomarkers related to muscle immune function, inflammation, and oxidative stress.

    Only peer-reviewed, randomized, double-blind, and placebo-controlled trials involving healthy adults were included in the systematic analysis. Postbiotic supplements used in these studies included paraprobiotics, Tyndallized probiotics, ghost biotics, heat-killed probiotics, inactivated probiotics, and nonviable probiotics. The different outcomes measured in these studies included exercise, exercise performance, and recovery.    

    Systematic review findings

    A total of 11 studies, including nine peer-reviewed papers and two conference abstracts, were included in the final review. These studies comprised a total of 477 participants and postbiotic supplementation periods ranging from 13 days to 12 weeks.

    Three studies directly compared the probiotic and postbiotic preparations of the same strains, including Lactiplantibaccilus plantarum TWK10, Lacticaseibacillus paracasei PS23, and Weizmannia coagulans GBI-30 6086.

    In one study investigating probiotic and postbiotic preparations of Weizmannia coagulans GBI-30 6086, none of the preparations were found to modulate the performance of healthy individuals participating in stressful lower-body exercises.

    Another comparative study showed that both probiotic and postbiotic preparations of Lacticaseibacillus paracasei PS23 can reduce the rate of muscle damage caused by maximal vertical jump, facilitate faster recovery, and improve fatigue as compared to placebo. However, only the postbiotic preparation was associated with a greater ability than the probiotic preparation to improve strength recovery.

    In one study investing probiotic and postbiotic preparations of Lactiplantibaccilus plantarum TWK10, both preparations similarly improved exercise performance. However, the probiotic preparation was superior than the postbiotic preparation in reducing glucose, lactate, and ammonia levels in response to exercise stimuli. This study also reported an increased inflammatory response to exercise in individuals supplemented with the postbiotic preparation.

    Another study investigating the effects of a postbiotic preparation of Weizmannia coagulans GBI-30 6086 reported enhanced lower body power and anti-inflammatory profiles in soldiers. Similarly, one study investigating a postbiotic preparation of Lactiplantibaccilus plantarum TWK10 revealed improvements in endurance performance, grip strength, and muscle mass in healthy exercising males.    

    Regarding other health benefits, one study investigating a postbiotic preparation of Lactobacillus gasseri OLL2809 observed preservation of natural killer cell activity and improvements in mood during strenuous exercise. Likewise, another study highlighted the ability of a postbiotic preparation of Lactococcus lactis JCM 5805 in improving antiviral responses and reducing the number of days with upper respiratory tract infection symptoms in athletes performing high-intensity training. Immunomodulatory and anti-inflammatory activities were also reported for the postbiotic preparation of Lacticaseibacillus paracasei MCC1849.   

    Significance

    Existing evidence suggests that postbiotics can be beneficial in improving mental health, reducing fatigue, and increasing the readiness of athletes across several weeks of exercise training. Thus, the current systematic review findings support the health and ergogenic benefits of postbiotic supplementation.

    Journal reference:

    • Kerksick, C. M., Moon, J. M., & Jager, R. (2024). It’s Dead! Can Postbiotics Really Help Performance and Recovery? A Systematic Review. Nutrients. doi:10.3390/nu16050720

    [ad_2]

    Source link

  • Exonate first-in-class eye drop Phase Ib/IIa trial data demonstrate safety and biological activity in treatment of diabetic retinopathy and diabetic macular oedema

    Exonate first-in-class eye drop Phase Ib/IIa trial data demonstrate safety and biological activity in treatment of diabetic retinopathy and diabetic macular oedema

    [ad_1]

    Exonate Ltd., a biotechnology company developing novel, non-invasive, small-molecule therapeutics for patients with retinal vascular diseases, today announced the data from a successful Phase Ib/IIa trial for lead candidate EXN407. These data demonstrate the safety and tolerability of EXN407, as well as clear indications of biological activity, positioning it well for further development as the first topical treatment for retinal vascular diseases such as diabetic retinopathy and diabetic macular oedema. Exonate is now planning to progress EXN407 to the CLEAR-DM (Clinical Evaluation of a New Eyedrop for Alleviating Retinopathy in Diabetic Macular Oedema) Phase IIb clinical trial.

    EXN407 is a twice-daily formulation, comprised of a small molecule SRPK1 inhibitor. The eye drop formula exploits SRPK1 involvement in the alternative splicing of vascular endothelial growth factor (VEGF), a protein heavily involved in the regulation of blood vessel growth. Through inhibition of SRPK1, EXN407 can selectively target pro-angiogenic isoforms of VEGF that lead to vascular retinal disease progression via aberrant growth of leaky blood vessels within the eye.

    The mild NPDR/DME (NCT04565756) clinical study assessed the safety, tolerability and signals of biological response to EXN407 monotherapy in a double-masked, placebo-controlled Phase Ib/IIa dose-ranging clinical trial in treatment-naïve patients with mild/moderate non-proliferative diabetic retinopathy (NPDR) and mild diabetic macular oedema. The independent Dose Escalation Committee characterised EXN407 as safe and well-tolerated, with 100% of patients completing the study without requiring anti-VEGF rescue, and no major or serious adverse events reported relating to EXN407. Moreover, EXN407 exhibited high levels of tolerability, with drop comfort scores similar to placebo and artificial tears.

    In addition to the primary safety and tolerability endpoints, the study concluded that there were promising signals of biological response from EXN407, demonstrating sustained decreases in macular thickness, relative to the placebo group and comparable to previously reported anti-VEGF injections. The trial further noted that EXN407 treatment led to a significant decrease in vascular leakage (60% of EXN407-treated patients relative to 20% placebo) and that EXN407 inhibited further increases to vascular leakage (10% of EXN407-treated patients relative to 50% placebo).

    “The Phase Ib/IIa data demonstrate the clear potential of EXN407 as a non-invasive treatment for these devastating, sight-threatening conditions, and the favourable safety profile and biological activity of EXN407 support its continued clinical development in retinal vascular diseases,” said Catherine Beech, chief executive officer of Exonate: “The results suggest that topical ocular EXN407 may provide clinical benefit and substantially reduce the injection burden for patients with diabetic eye disease. We look forward to engaging with strategic partners to support the CLEAR-DM phase IIb trial, which has been designed to fully demonstrate the clinical benefits of EXN407 in NPDR/DME.”

    Full results of the Phase Ib/IIa will be presented at the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) in May 2024: https://www.arvo.org/annual-meeting/

    To find out more information about Exonate’s therapeutic pipeline for diabetic complications and other indications, as well as our clinical programmes, please visit: https://www.exonate.com/ 

    [ad_2]

    Source link

  • Can the modulation of the gut microbiome using a prebiotic improve muscle function and cognition?

    Can the modulation of the gut microbiome using a prebiotic improve muscle function and cognition?

    [ad_1]

    In a recent study published in Nature Communications, researchers examined the efficacy of a prebiotic in improving muscular and cognitive performance vs. a placebo among elderly individuals.

    Study: Effect of gut microbiome modulation on muscle function and cognition: the PROMOTe randomised controlled trial. Image Credit: Tatiana Shepeleva/Shutterstock.com
    Study: Effect of gut microbiome modulation on muscle function and cognition: the PROMOTe randomised controlled trial. Image Credit: Tatiana Shepeleva/Shutterstock.com

    Background

    As the world’s population ages, age-related disorders such as muscle loss and cognitive impairment become more common. Researchers and physicians must acknowledge cognitive changes as part of healthy aging. Exercise can help reduce muscle loss, although elderly individuals may struggle. Interventions with physical and mental advantages are required.

    According to recent studies, alterations in the gut microbiota might influence muscle physiology and cognitive function, potentially altering anabolic resistance in older muscles and cognition. Prebiotics are associated with improved health in older individuals.

    About the study

    In the present study, researchers explored the role of gut microbiota regulation in enhancing cognition and muscular function benefits from protein supplementation and exercise in elders.

    The team conducted the PRebiotic and PrOtein on Muscle in Older Twins (PROMOTe) trial remotely using video visits, online surveys, cognitive tests, and the sending of equipment and biological samples. Participants were aged ≥60 years and had a low protein consumption of <1.0 g per kg weight per day, as established by the TwinsUK group.

    The team excluded participants with severe food allergies, ongoing or recent antibiotic use, protein supplementation, prebiotics and probiotics, and advanced renal disease. They also excluded individuals with a weight reduction of ≥5.0% of body weight in the previous year, major surgery or injury that could alter physical functions, and current participation in other interventional trials.

    The team randomized twin pairs to receive either a placebo (7.5g maltodextrin) or a prebiotic (intervention, 3.4 g inulin and 3.5 g fructo-oligosaccharides) daily for 12 weeks. They provided all individuals with 3.3g of branched-chain-type amino acid (BCAA) supplementation and resistance training. The primary objective was to reduce chair rise time (the time required to do five chair raises without using arms). Secondary outcomes included the cognitive battery factor score, the SPPB score (including chair rise time and gait speed), grip strength, gait speed, physical activity levels assessed using the International Physical Activity Questionnaire (IPAQ), and the Simplified Nutritional Assessment Questionnaire (SNAQ) appetite scale.

    The participants completed the Short Physical Performance Battery (SPPB) remotely, including chair rise time and handgrip strength evaluations with a dynamometer with real-time instructions from a qualified researcher. The participants provided stool samples to extract microbial DNA for gut microbiota characterization by shotgun metagenomic sequencing. The CANTAB battery includes cognitive tests for executive function, spatial working memory, and memory. The team evaluated three days of food diary data. They conducted intention-to-treat (ITT), per-protocol (PP), and heritability analyses.

    Results

    Of 626 eligible individuals, 72 were successfully recruited (36 twin pairs). The participants had a mean age of 73 and were 78% female. There were more moderate adverse effects (like abdominal bloating) in the intervention group compared to the placebo group; however, the team found no compliance-related differences, indicating that the supplements were generally well accepted. In either arm, no participants stated gastrointestinal side effects as a cause for non-adherence to the research intervention. No critical adverse effects occurred.

    There were no significant changes in findings between the PP and ITT models. The team found no significant differences between the study groups concerning primary or secondary outcomes. The intervention group outperformed the placebo group in terms of cognition first-factor scores. Furthermore, the specific cognition assessment paired associations learning showed considerably fewer errors in the intervention group than in the placebo group.

    Using Bray-Curtis dissimilarity, twin pairs’ microbiotas were considerably more similar to the microbiota compositions of unrelated people at baseline and the conclusion of the research. The alpha and beta diversity assessments revealed no significant changes between the prebiotic and placebo groups. Compositional bias-adjusted linear modeling controlling for twin- and arm-pair-associated effects showed 144 microbiota characteristics, including 109 microbiome taxa, 33 microbe functions, richness, and Faith’s phylogenetic diversity strongly associated with chair rise time.

    Correlation analysis of changes in microbiota characteristics and chair rise times throughout the research intervention period demonstrated a link between chair rise duration improvement and changes in richness, Shannon diversity, and Faith’s diversity. The study found 11 significant differences between the prebiotic and placebo groups, with the prebiotic group having higher levels of Bifidobacterium, Actinobacteria, Firmicutes, Bacteroidetes, and Phocea massiliensis. Eight microbiome traits were associated with cognitive capacity, including an increase in actinobacteria and improvements in cognition component scores.

    Conclusion

    Overall, the study found that gut microbiome manipulations can enhance cognition in elders, demonstrating the viability of remote trials for older adults. The prebiotic intervention, which was well tolerated and altered gut microbiota, increased the quantity of Bifidobacterium. However, there were no significant changes in chair rise times between the study groups. Future larger-scale research should explore the possibility of gut microbiome-targeted therapies to overcome age-related anabolic resistance.

    [ad_2]

    Source link

  • Omalizumab boosts tolerance to multiple food allergies, study finds

    Omalizumab boosts tolerance to multiple food allergies, study finds

    [ad_1]

    In a recent study published in The New England Journal of Medicine, a group of researchers evaluated the efficacy and safety of omalizumab as a standalone treatment in increasing the allergen tolerance of individuals with multiple food allergies.

    Study: Omalizumab for the Treatment of Multiple Food Allergies. Image Credit: Dejan Stanisavljevic / ShutterstockStudy: Omalizumab for the Treatment of Multiple Food Allergies. Image Credit: Dejan Stanisavljevic / Shutterstock

    Background 

    Food allergies affect a significant portion of the United States (U.S.) population, leading to a high demand for vigilance and negatively impacting individuals’ well-being and healthcare costs. The only Food and Drug Administration (FDA)-approved treatment, oral immunotherapy for peanut allergies, is complex and can cause adverse effects. Omalizumab, an Immunoglobulin-E (IgE)-targeting monoclonal antibody approved for other allergic conditions, shows potential in managing multiple food allergies by improving allergen tolerance, reducing reactions, and enhancing life quality. However, further research is needed to confirm omalizumab’s long-term safety, effectiveness, and the best dosing for treating various food allergies in different demographics.

    About the study 

    The Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen Oral Immunotherapy (OIT) in Food Allergic Children and Adults (OUtMATCH) 

    The OUtMATCH trial, a multi-stage, double-blind, placebo-controlled study at ten U.S. centers, explores omalizumab’s efficacy against food allergies. Developed in collaboration with the Consortium for Food Allergy Research and pharmaceutical giants, its protocols ensure rigorous evaluation and safety, overseen by Johns Hopkins University’s review board. After completing its initial phase, the trial progresses to assess long-term outcomes and dietary reintroduction post-treatment.

    Participants, ranging from 1 to 55 years old and allergic to peanuts and at least two other specified foods, underwent thorough screening and challenges to ascertain eligibility. The initial phase involved a 2:1 randomization to either omalizumab or placebo, followed by reevaluation through food challenges. An interim analysis, prompted by the coronavirus disease 2019 (COVID-19) pandemic’s impact on enrollment, affirmed omalizumab potential, leading to an adjusted final sample size.

    The statistical analysis utilized a two-sided Fisher’s exact test to assess the efficacy of the treatment by comparing the percentage of participants who could ingest targeted food doses without adverse symptoms. To address multiple comparison issues, gatekeeping and sequential testing strategies were employed, ensuring a family-wise error rate below 0.05. The interim analysis, indicating positive outcomes, led to the cessation of enrollment. Secondary endpoints are presented with 95% confidence intervals, specifically focusing on the pediatric cohort, which constituted the primary analysis group.

    Study results 

    In the comprehensive evaluation spanning from September 2019 through November 2022, the trial screened 435 children and adolescents for eligibility. Of these, 177 were randomized to either the omalizumab or placebo group, with the majority of exclusions resulting from insufficient allergic responses to the tested foods. The demographic makeup of participants was predominantly male, with a median age of seven years. These individuals were notably atopic, suffering from conditions such as asthma, atopic dermatitis, and allergic rhinitis, and had a median total IgE level of 700 IU per milliliter. Baseline food challenge tests showed similar maximum tolerated doses across the board for the allergens in question.

    The trial’s omalizumab group saw a significant percentage (67%) of participants able to consume at least 600 mg of peanut protein without dose-limiting symptoms, starkly contrasting with only 7% in the placebo group. This efficacy extended to other specified foods, demonstrating omalizumab’s potential to significantly raise allergen tolerance levels among recipients. The dosage varied among participants, with a notable division in administration frequency based on individual requirements.

    Further analysis within the trial assessed the capability of participants to ingest one, two, or three of the specified allergens in varying doses without adverse effects. Results from the omalizumab group were promising, showing a substantial capacity for increased allergen consumption. An open-label extension of the trial aimed to investigate the durability of omalizumab’s efficacy over a more extended period (40 to 44 weeks), revealing that most participants maintained or improved their allergen tolerance levels.

    Quality of life assessments for both participants and caregivers, conducted via validated questionnaires, indicated no significant change by the end of the initial trial stage. However, improvements were noted during the open-label extension. Safety profiles were similar across both groups, with the exception of more frequent injection-site reactions among omalizumab recipients. One serious adverse event was reported, considered possible but unlikely related to omalizumab.

    The trial faced challenges due to the COVID-19 pandemic, which temporarily disrupted participant recruitment and treatment administration. Additionally, mold contamination in some food challenge products necessitated a brief pause in testing, although subsequent analyses confirmed that these issues did not impact the trial’s overall results. 

    Conclusions 

    To summarize, omalizumab significantly raised the tolerance threshold for multiple food allergens, including peanuts, cashews, eggs, and milk, among individuals from as young as 1 year old over 16 weeks. A majority of those treated with omalizumab could safely ingest quantities of allergens far exceeding typical accidental exposure levels, indicating its potential as an effective monotherapy for food allergies. The treatment also demonstrated the ability to simultaneously protect against reactions from multiple allergens. Extended treatment in a 24-week follow-up showed sustained tolerance.

    [ad_2]

    Source link

  • Omalizumab shows promise in preventing food allergy reactions in children, study finds

    Omalizumab shows promise in preventing food allergy reactions in children, study finds

    [ad_1]

    A drug can make life safer for children with food allergies by preventing dangerous allergic responses to small quantities of allergy-triggering foods, according to a new study led by scientists at the Stanford School of Medicine.

    The research will be published Feb. 25 in the New England Journal of Medicine. The findings suggest that regular use of the drug, omalizumab, could protect people from severe allergic responses, such as difficulty breathing, if they accidentally eat a small amount of a food they are allergic to.

    I’m excited that we have a promising new treatment for multifood allergic patients. This new approach showed really great responses for many of the foods that trigger their allergies.”


    Sharon Chinthrajah, MD, study’s senior author, associate professor of medicine and of pediatrics, and the acting director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford Medicine

    “Patients impacted by food allergies face a daily threat of life-threatening reactions due to accidental exposures,” said the study’s lead author, Robert Wood, MD, professor of pediatrics at Johns Hopkins University School of Medicine. “The study showed that omalizumab can be a layer of protection against small, accidental exposures.”

    Omalizumab, which the Food and Drug Administration originally approved to treat diseases such as allergic asthma and chronic hives, binds to and inactivates the antibodies that cause many kinds of allergic disease. Based on the data collected in the new study, the FDA approved omalizumab for reducing risk of allergic reactions to foods on Feb. 16.

    All study participants were severely allergic to peanuts and at least two other foods. After four months of monthly or bimonthly omalizumab injections, two-thirds of the 118 participants receiving the drug safely ate small amounts of their allergy-triggering foods. Notably, 38.4% of the study participants were younger than 6 years, an age group at high risk from accidental ingestions of allergy-triggering foods.

    Allergies are common

    Food allergies affect about 8% of children and 10% of adults in the United States. People with severe allergies are advised to fully avoid foods containing their allergy triggers, but common allergens such as peanuts, milk, eggs and wheat can be hidden in so many places that everyday activities such as attending parties and eating in restaurants can be challenging.

    “Food allergies have significant social and psychological impacts, including the threat of allergic reactions upon accidental exposures, some of which can be life-threatening,” Chinthrajah said. Families also face economic impacts from purchasing more expensive foods to avoid allergens, she added.

    In the best available treatment for food allergies, called oral immunotherapy, patients ingest tiny, gradually increasing doses of allergy-triggering foods under a doctor’s supervision to build tolerance. But oral immunotherapy itself can trigger allergic responses, desensitization to allergens can take months or years, and the process is especially lengthy for people with several food allergies, as they are usually treated for one allergy at a time. Once they are desensitized to an allergen, patients also must continue to eat the food regularly to maintain their tolerance to it -; but people often dislike foods they were long required to avoid.

    “There is a real need for treatment that goes beyond vigilance and offers choices for our food allergic patients,” Chinthrajah said.

    Omalizumab is an injected antibody that binds and deactivates all types of immunoglobin E, or IgE, the allergy-causing molecule in the blood and on the body’s immune cells. So far, omalizumab appears able to provide relief from multiple food allergens at once.

    “We think it should have the same impact regardless of what food it is,” Chinthrajah said.

    The study included 177 children with at least three food allergies each, of whom 38% were 1 to 5 years old, 37% were 6 to 11 years old, and 24% were 12 or older. Participants’ severe food allergies were verified by skin-prick testing and food challenges; they reacted to less than 100 milligrams of peanut protein and less than 300 milligrams of each other food.

    Two-thirds of the participants were randomly assigned to receive omalizumab injections, and one-third received an injected placebo; the injections took place over 16 weeks. Medication doses were set based on each participant’s body weight and IgE levels, with injections given once every two or four weeks, depending on the dose needed. The participants were re-tested between weeks 16 and 20 to see how much of each allergy-triggering food they could safely tolerate.

    Upon re-testing, 79 patients (66.9%) who had taken omalizumab could tolerate at least 600 mg of peanut protein, the amount in two or three peanuts, compared with only four patients (6.8%) who had the placebo. Similar proportions of patients showed improvement in their reactions to the other foods in the study.

    About 80% of patients taking omalizumab were able to consume small amounts of at least one allergy-triggering food without inducing an allergenic reaction, 69% of patients could consume small amounts of two allergenic foods and 47% could eat small amounts of all three allergenic foods.

    Omalizumab was safe and did not cause side effects, other than some instances of minor reactions at the site of injection. This study marks the first time its safety has been assessed in children as young as 1.

    More questions

    More research is needed to further understand how omalizumab could help people with food allergies, the researchers said.

    “We have a lot of unanswered questions: How long do patients need to take this drug? Have we permanently changed the immune system? What factors predict which people will have the strongest response?” Chinthrajah said. “We don’t know yet.”

    The team is planning studies to answer these questions and others, such as finding what type of monitoring would be needed to determine when a patient gains meaningful tolerance to an allergy-triggering food.

    Many patients who have food allergies also experience other allergic conditions treated by omalizumab, Chinthrajah noted, such as asthma, allergic rhinitis (hay fever and allergies to environmental triggers such as mold, dogs or cats, or dust mites) or eczema. “One drug that could improve all of their allergic conditions is exactly what we’re hoping for,” she said.

    The drug could be especially helpful for young children with severe food allergies, she added, because they tend to put things in their mouths and may not understand the dangers their allergies pose, she added.

    The drug could also make it safer for community physicians to treat food allergy patients, since it cannot trigger dangerous allergic reactions, as oral immunotherapy sometimes does. “This is something that our food allergy community has been waiting a long time for,” Chinthrajah said. “It’s an easy drug regimen to implement in a medical practice, and many allergists are already using this for other allergic conditions.”

    The research team included scientists from the Johns Hopkins University School of Medicine, the National Institutes of Allergy and Infectious Diseases, the Icahn School of Medicine at Mount Sinai, Massachusetts General Hospital, the University of North Carolina School of Medicine, the University of Arkansas for Medical Sciences and Arkansas Children’s Hospital, Emory University School of Medicine and Children’s Healthcare of Atlanta, University of Texas Southwestern Medical Center, Perelman School of Medicine at the University of Pennsylvania, Genentech/Roche, Novartis Pharmaceuticals Corporation, and Rho, Inc.

    The research was funded by the National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, both part of the National Institutes of Health (grant numbers UM2AI130836, UM1AI130838, UL1TR003098, UM1TR004408, UM1AI130570, UM1AI130839, UM1AI130936, UM1TR004406, UL1TR002535, UM1TR004399, UL1TR001878, UM1AI130781, UL1TR002378 and UL1TR003107), and the Claudia and Steve Stange Family Fund. Genentech/Novartis provided the investigational product and monetary support to Johns Hopkins University and collaborated on the study design.

    Source:

    Journal reference:

    Wood, R. A., et al. (2024) Omalizumab for the Treatment of Multiple Food Allergies. New England Journal of Medicine. doi.org/10.1056/NEJMoa2312382.

    [ad_2]

    Source link

  • Red light therapy shown to significantly reduce blood sugar spikes, study finds

    Red light therapy shown to significantly reduce blood sugar spikes, study finds

    [ad_1]

    In a recent study published in the Journal of Biophotonics, scientists examined whether photobiomodulation of healthy subjects using red light of 670 nm wavelength impacted the circulating glucose levels in the plasma, using oral glucose tolerance tests.

    Study: Light stimulation of mitochondria reduces blood glucose levels. Image Credit: AlteredR/Shutterstock.comStudy: Light stimulation of mitochondria reduces blood glucose levels. Image Credit: AlteredR/Shutterstock.com

    Background

    Mitochondria are the organelles that carry out cellular respiration, using glucose and oxygen to produce adenosine triphosphate or ATP, the energy currency. The ability of the mitochondria to produce ATP reduces naturally with age and due to diseases.

    However, studies have found that the production of ATP can be increased through photobiomodulation using light in the visible and near-infrared ranges, between 650 nm and 900 nm.

    Photobiomodulation is also known to decrease reactive oxygen species levels, and this ability is believed to be conserved across species in the animal kingdom.

    Cytochrome C oxidase, which is part of the electron transport chain in the mitochondrial membrane, absorbs these longer wavelengths of light, increasing the membrane potential and production of ATP.

    Research has shown that photobiomodulation has brought about significant increases in regions of the body undergoing high levels of metabolic activity, such as the retina and the central nervous system.

    The increased ATP production could also increase the uptake of glucose, which might be evident in changes in the plasma glucose levels.

    About the study

    In the present study, the researchers used a standard glucose tolerance test to determine whether photobiomodulation using 670 nm light decreased blood glucose levels in healthy human subjects.

    The study included 30 healthy participants with no known medical conditions, half of whom underwent photobiomodulation with 670 nm light, and the other half were in the placebo group with no light.

    All the participants underwent an oral glucose tolerance test at the onset of the study, where they consumed 75 g of glucose dissolved in 150 mL of water, and finger prick blood samples were used to record the blood glucose levels.

    A second oral glucose tolerance test was administered after a week when the participants were administered the placebo or the intervention.

    About 45 minutes before the second oral glucose tolerance test was administered, the participants in the intervention group were exposed to 670 nm light for 15 minutes, while those in the placebo group were identically positioned but not exposed to the 670 nm light.

    The oral glucose tolerance tests were administered only after ensuring that the participants had fasted overnight.

    After consuming glucose dissolved in water, blood glucose concentrations and the end-tidal carbon dioxide (EtCO2) partial pressure were recorded every quarter of an hour for two hours when the participants were at rest.

    The 670 nm light exposure was directed at an 800 cm2 region in the upper back, using light-emitting diodes with a shield to prevent light leakage.

    The glucose tolerance test results were compared between the participants in the intervention and placebo groups.

    Additionally, participants in the intervention group were compared to each other, and similar comparisons were made within the placebo group for paired-participant analysis to account for individual variations.

    Results

    The results showed that exposure to 670 nm of light over 15 minutes resulted in a 27.7% decrease in glucose levels averaged over two hours.

    Additionally, a 7.5% decrease was also observed in maximum glucose spiking within the intervention group, and a 12.1% difference in peak glucose levels was seen between the placebo and intervention groups.

    The paired-participant analysis within the placebo group also showed no difference in the blood glucose levels between the two measurements.

    The impact of the light exposure was significant after approximately an hour and a half of local light exposure alone. The impact of this local light exposure on plasma glucose levels indicates an abscopal effect, where mitochondria in distal organs are also impacted.

    The researchers also discussed the potential mechanisms through which local light exposure could have such widespread impact, including the role of circulating cytokines and cell-free mitochondria in the blood that are competent to conduct cellular respiration.

    Conclusions

    To summarize, the findings showed that local exposure to 670 nm light for 15 minutes significantly reduced plasma and peak glucose levels.

    While these results have proven that longer wavelengths of light have a positive effect on mitochondrial function in healthy humans, the potential use of light exposure in helping regulate blood glucose levels in patients with diabetes needs to be explored.

    [ad_2]

    Source link

  • New RNA therapy zilebesiran shows promise in lowering blood pressure

    New RNA therapy zilebesiran shows promise in lowering blood pressure

    [ad_1]

    In a recent study published in JAMA, researchers evaluated the efficacy and safety of zilebesiran doses in reducing mild to moderate hypertension.

    Study: RNA Interference With Zilebesiran for Mild to Moderate Hypertension - The KARDIA-1 Randomized Clinical Trial. Image Credit: Ground Picture / ShutterstockStudy: RNA Interference With Zilebesiran for Mild to Moderate Hypertension – The KARDIA-1 Randomized Clinical Trial. Image Credit: Ground Picture / Shutterstock

    Background 

    Hypertension is a major global health issue, leading to cardiovascular mortality and kidney disease progression, with up to 80% of patients failing to achieve recommended blood pressure (BP) targets. This condition’s management is complicated by significant variability in BP and the challenges of ensuring adherence to daily, multi-drug treatment regimens. Zilebesiran, an innovative ribonucleic acid (RNA) interference therapeutic, targets the liver’s production of angiotensinogen, a crucial component in BP regulation. Early phase studies showed promising results, with zilebesiran leading to sustained BP reductions. Further research is needed to fully understand the long-term effects, optimal dosing, and safety profile of zilebesiran in diverse patient populations.

    About the study 

    The present study was conducted across Canada, Ukraine, the United Kingdom (UK), and the United States (US) from July 2021 to June 2023 and adhered to ethical standards, requiring informed consent from participants. It targeted adults with hypertension, excluding those with certain conditions like severe renal impairment or poorly controlled diabetes. After a washout period for previous antihypertensives, participants were randomized to receive one of four zilebesiran dosing regimens or a placebo, with efforts to maintain blinding and stratification based on race and baseline systolic blood pressure (SBP).

    The study’s primary focus was on the change from baseline to month 3 in 24-hour mean ambulatory SBP among different zilebesiran doses compared to placebo. Secondary outcomes included office SBP changes, the percentage of patients achieving specific SBP criteria without additional medication, and various blood pressure metrics. Ambulatory and office BP measurements were conducted using standardized devices, and serum angiotensinogen levels were evaluated for pharmacodynamic assessment. Safety was monitored through adverse event reporting and laboratory tests.

    The statistical analysis sought to identify significant SBP reductions across treatment groups, using a structured approach for handling multiple comparisons and missing data. It comprehensively evaluated zilebesiran’s efficacy and safety in hypertension management across diverse demographics.

    Study results 

    In the study, 1,517 individuals were initially considered, with 394 ultimately randomized to receive either placebo or varying doses of zilebesiran: 150 mg, 300 mg every 6 months, 300 mg every 3 months, or 600 mg every 6 months. One patient did not receive the assigned treatment, leading to 393 participants being dosed. The analysis excluded data from 16 patients due to data collection issues related to the ongoing war in Ukraine, resulting in 377 individuals (302 on zilebesiran and 75 on placebo) being evaluated, with 347 completing the 6-month period.

    The participants’ demographics were diverse, with 44.3% female and 24.7% Black individuals and an average age of 56.8 years. Baseline BP averaged 142/82 mm Hg. The primary outcome showed significant reductions in 24-hour mean ambulatory SBP at 3 months across zilebesiran doses compared to placebo, with least-squares mean (LSM) changes from baseline of -7.3 mm Hg for 150 mg every 6 months, -10.0 mm Hg for 300 mg (both intervals), and -8.9 mm Hg for 600 mg every 6 months, versus a 6.8 mm Hg increase in the placebo group.

    Secondary outcomes at 3 months mirrored these findings, with reductions in office SBP and consistent benefits observed at 6 months. Notably, zilebesiran significantly outperformed placebo in terms of participants meeting pre-defined BP response criteria. Additional benefits included substantial reductions in diastolic BP (DBP) and serum angiotensinogen levels, illustrating zilebesiran’s potent and sustained action.

    Exploratory analyses revealed a lower need for rescue antihypertensive medications in those treated with zilebesiran compared to placebo. Safety profiles were favorable, with serious adverse events (AEs) reported in a smaller percentage of zilebesiran-treated patients compared to placebo. Most AEs were mild to moderate, including injection site reactions and hyperkalemia. There were no significant liver function test abnormalities, and instances of hypotension and hyperkalemia were generally mild and manageable.

    Body weight changes were minimal across all groups, and a slight increase in serum potassium levels was noted in some zilebesiran recipients, though these instances were typically transient and manageable. 

    Conclusions 

    To summarize, zilebesiran demonstrated significant BP reductions with the potential for biannual dosing. This novel treatment, leveraging RNA interference to decrease hepatic angiotensinogen, showed promise over a six-month period, particularly at doses of 300 mg or higher. AEs, mainly mild, included injection site reactions and hyperkalemia. The findings suggest that zilebesiran could simplify hypertension management, enhancing treatment adherence and efficacy. Further investigation is required to assess long-term safety and efficacy, including combination with other therapies, as explored in the ongoing KARDIA-2 study.

    [ad_2]

    Source link

  • Melatonin treatment does not affect insulin resistance of night shift workers

    Melatonin treatment does not affect insulin resistance of night shift workers

    [ad_1]

    Melatonin treatment does not affect the insulin resistance or the glucose tolerance of night shift workers, according to a new study from the University of Surrey and the University Medical Centre Hamburg. Melatonin treatment does, however, significantly improve the sleep quality of those working shifts.

    In this study, scientists explored how oral melatonin affects insulin resistance and blood pressure in night shift workers, who face a higher risk of Type 2 diabetes. Insulin resistance is when cells struggle to absorb glucose from the blood. Previous research suggests melatonin could help these workers’ glucose tolerance and heart health. This led scientists to investigate melatonin’s broader effects on the body.

    Night shift work is necessary for our emergency and health services and to keep our economy moving. However, working night shifts disrupt our circadian rhythms, which are driven by light/dark cycles and are associated with sleep disturbances, cardiometabolic diseases and increased risk of diabetes.


    We need to find ways to limit the adverse health implications for night shift workers so they can continue in their roles whilst protecting their long-term health.”


    Debra Skene, Professor of Neuroendocrinology, University of Surrey

    To investigate the impact of melatonin, 24 night shift workers and 12 healthy non-shift workers were recruited and underwent glucose tolerance testing and blood pressure monitoring for 24 hours. Night shift workers were then randomised to receive oral melatonin (2 mg) or a placebo at night time or in the morning, depending on their shift schedule, for 12 weeks.

    The authors identified that night shift workers were significantly more insulin-resistant than non-night shift workers. After 12 weeks of taking the hormone melatonin, no significant effect was observed in serum glucose or insulin concentrations, which are markers of insulin resistance. Similarly, for blood pressure, treatment with melatonin had no significant effect.

    Unsurprisingly, melatonin significantly improved the sleep quality of night shift workers. During the initial assessment, only 21 per cent of night shift workers described their sleep quality as good; however, after 12 weeks of melatonin treatment, 50 per cent of this cohort indicated good sleep quality. The proportion of good versus poor sleepers remained almost unchanged in the placebo group.

    Professor Skene added:

    “The benefits of improved sleep for shift workers via melatonin are undeniable, and people should feel more rested and alert. However, since there is no evidence that the use of melatonin reduces insulin resistance, we need to find alternate ways to improve insulin resistance and lessen the likelihood of a person developing type 2 diabetes.”

    This study was published in the journal Pharmacological Research.

    Source:

    Journal reference:

    Hannemann, J., et al. (2024). Effect of oral melatonin treatment on insulin resistance and diurnal blood pressure variability in night shift workers. A double-blind, randomized, placebo-controlled study. Pharmacological Research. doi.org/10.1016/j.phrs.2023.107011.

    [ad_2]

    Source link

  • Stapokibart shows promise in reducing nasal congestion in seasonal allergy patients, study finds

    Stapokibart shows promise in reducing nasal congestion in seasonal allergy patients, study finds

    [ad_1]

    In a recent study published in EClinicalMedicine, researchers assessed the efficacy and safety of stapokibart as an add-on therapy in patients with moderate-to-severe uncontrolled seasonal allergic rhinitis (SAR).

    Study: Efficacy and safety of stapokibart (CM310) in uncontrolled seasonal allergic rhinitis (MERAK): an investigator-initiated, placebo-controlled, randomised, double-blind, phase 2 trial. Image Credit: wavebreakmedia/Shutterstock.comStudy: Efficacy and safety of stapokibart (CM310) in uncontrolled seasonal allergic rhinitis (MERAK): an investigator-initiated, placebo-controlled, randomised, double-blind, phase 2 trial. Image Credit: wavebreakmedia/Shutterstock.com

    Background 

    Allergic rhinitis (AR), affecting up to half the global population, is an Immunoglobulin E (IgE)-mediated inflammatory condition of the nasal mucosa, leading to symptoms like sneezing, congestion, and often ocular discomfort.

    It poses a significant socio-economic burden, with costs reaching €50 billion annually. AR divides into SAR and perennial forms, with SAR, triggered by outdoor pollen, showing higher inflammation and more severe symptoms.

    Despite treatments like antihistamines and corticosteroids, over 60% of SAR patients report inadequate symptom control. Biologics targeting type 2 inflammation, such as omalizumab, have shown benefits, yet their role in post-standard care remains unclear.

    Further research is needed to conclusively determine the effectiveness and safety of biological treatments in managing uncontrolled SAR and to optimize patient care strategies.

    About the study 

    In the present comprehensive phase 2 trial conducted across six sites in China, researchers embarked on a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of stapokibart in treating SAR.

    Participants, aged 18 to 65 with a documented history of SAR and insufficient response to conventional treatments, were randomized in a 1:1:1 ratio to receive stapokibart 300 mg either weekly or biweekly or a placebo, alongside mometasone furoate nasal spray and oral loratadine over a 4-week treatment period, followed by an 8-week follow-up.

    The study rigorously adhered to ethical standards, following the Declaration of Helsinki and Good Clinical Practice, with ethics committee approvals from each center.

    It strictly selected participants with confirmed SAR, significant pollen exposure, and considerable baseline symptoms. It used comprehensive assessments via the Rhinoconjunctivitis Quality-of-Life Questionnaire, including daily nasal and ocular symptom scores and life quality.

    It thoroughly analyzed efficacy and safety, focusing on nasal symptom changes over two weeks, alongside secondary evaluations of symptom variations, life quality, and treatment timings. Safety was closely monitored, including adverse events, lab tests, and vital signs.

    Statistical analyses were conducted with precision, aiming to demonstrate the superiority of stapokibart over placebo with adjusted type I error rates.

    A sample size calculation ensured adequate power to detect significant differences, accounting for potential dropouts.

    Efficacy endpoints were analyzed using an Analysis of Covariance (ANCOVA) model, with a rigorous plan for handling missing data and ensuring robust results. 

    Study results 

    Between August 17 and December 28, 2022, the present study screened 172 patients for SAR, enrolling 93 from four centers, with 92 receiving treatment. The participants, averaging 37 years old and mostly female, had SAR for an average of 7.6 years.

    Despite treatment, stapokibart did not significantly outperform placebo in reducing total nasal symptom scores (rTNSS) over two weeks.

    However, when administered biweekly, stapokibart showed notable improvement in nasal congestion and ocular symptoms, with significant reductions in both nasal and ocular symptom scores compared to placebo. 

    The study observed mild to moderate treatment-emergent adverse events, with a lower incidence in the stapokibart groups compared to placebo.

    Further exploratory analyses illuminated that biweekly stapokibart led to more days with mild or no symptoms, alongside a noteworthy decrease in inflammation markers.

    Especially notable was the discovery from subgroup analyses that individuals with higher initial eosinophil counts exhibited more pronounced benefits from the biweekly stapokibart regimen.

    Despite the primary outcomes not demonstrating significant differences, the study’s secondary and exploratory findings hint at stapokibart’s potential advantages, particularly for patients with elevated eosinophil levels.

    This insight propels the argument for additional research into stapokibart’s role in treating SAR, suggesting that its real value may lie in a more targeted application based on specific patient profiles.

    Conclusions 

    To summarize, the trial found that while stapokibart, administered either weekly or biweekly, did not significantly change total nasal symptom scores over placebo, it effectively improved nasal and ocular symptom scores in SAR patients, especially those with high eosinophil counts.

    It was the first to assess biologics as an add-on during pollen exposure for patients with uncontrolled SAR.

    Subgroup analysis revealed significant symptom improvements in patients with high eosinophil levels, aligning with stapokibart’s targeted inflammation mechanism.

    Despite a generally well-tolerated safety profile, no linear dose-response relationship was observed, highlighting the need for further research.

    [ad_2]

    Source link

  • Combining clot busters and blood thinners shows no advantage for people with ischemic strokes

    Combining clot busters and blood thinners shows no advantage for people with ischemic strokes

    [ad_1]

    Giving blood thinners in addition to clot-busting medications to people with ischemic strokes (clot-caused strokes) did not improve their outcomes 90 days later, according to preliminary late-breaking science presented today at the American Stroke Association’s International Stroke Conference 2024. The meeting, held in person in Phoenix, Feb. 7 – 9, 2024, is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

    These results are from the MOST (Multi-Arm Optimization of Stroke Thrombolysis) trial. MOST is a 57-center U.S. trial that was halted after an independent data and safety board analyzed results on the first 500 patients out of a planned 1,200 participants and determined it highly unlikely that a benefit would be found if the research was completed. The study was looking for improvement in functional outcomes at 90 days.

    When we began the trial, we believed the medications would improve outcomes, so we were surprised with the negative results. However, we designed the trial to allow us to efficiently answer the question for two blood-thinning medications in one trial. We have definitely done that and are pleased with the ability to answer this question.”

    Opeolu M. Adeoye, M.D., M.S., lead author of the study and BJC HealthCare Distinguished Professor of Emergency Medicine and chair of the department of emergency medicine at Washington University School of Medicine in St. Louis, Missouri

    “A lot of our approaches in stroke treatment were learned from how we treat heart attacks. In previous trials, we first tested to make sure these medications were safe for use in stroke and then launched MOST to confirm their safety and test whether they would work to improve functional outcomes and reduce disability after stroke,” Adeoye said.

    The MOST trial enrolled adults with ischemic stroke severe enough that rehabilitation would likely be needed. All participants received a standard clot-busting medication to dissolve the clot (thrombolysis) within three hours of stroke onset. Participants were then randomized to one of three groups for additional treatment: one group received the blood thinner argatroban within 75 minutes of the clot-busting medication, followed by a 12-hour infusion of argatroban. A second group received an initial dose of the blood thinner eptifibatide within 75 minutes of the clot-busting medication, followed by a 2-hour infusion of eptifibatide and a 10-hour infusion of saline placebo. The control group received a clot buster and a placebo treatment (a 12-hour infusion of intravenous saline solution containing neither of the blood-thinning medications).

    The primary outcome was the study participant’s level of physical function at 90 days after ischemic stroke. Physical function levels were assessed using the modified Rankin score, or mRS, a 6-point disability scale. The videotaped assessment was judged by an independent neurologist reviewer who was not aware of which treatment patients had received. The mRS score was translated into a utility-weighted mRS, using validated ratings of functional outcomes by patients and physicians, resulting in a 0 to 10-point scale in which a higher score means a greater benefit from the treatment. The interim analysis was planned at the start of the study and scheduled to take place after 500 patients were enrolled. In addition, a data safety and monitoring board (DSMB) reviewed safety data after every 30 patients enrolled, looking particularly for occurrences of bleeding in the brain.

    In the 514 patients enrolled prior to the trial being halted by the DSMB in July 2023, the analysis found:

    • The two blood thinners used did not significantly increase the risk of bleeding into the brain.
    • However, neither of the two blood thinners improved outcomes in the stroke survivors. On the 0 to 10 utility-weighted mRS scale, patients receiving placebo averaged 6.8, those receiving argatroban averaged 5.2, and those receiving eptifibatide averaged 6.3. (Types of disability will vary, however, people with a utility-weighted mRS scale of 6 are expected to have difficulty performing activities of daily living without assistance or support.)

    Study details and background:

    • The three-arm study was conducted at 57 hospitals in the United States between October 2019 and July 2023.
    • Participants all had ischemic (clot-caused) stroke that rated a 6 or higher on the National Institutes of Health Stroke Severity Scale and considered a moderately severe stroke.
    • 514 adults were enrolled in the trial before it was halted; participants were an average age of 68; about 50% were women; and about 25% identified as Black adults.
    • Participants were treated within three hours after the onset of stroke symptoms (or the last time seen well) using the standard-of-care approach of thrombolysis (delivering clot-busting medications to dissolve the clot).
    • In addition, 44% of the patients across all three groups were treated with interventional removal of their clots called thrombectomy.
    • At the time of enrollment, participants were randomized to receive a blood thinner or placebo within 75 minutes of thrombolysis: 59 received argatroban; 228 received eptifibatide; and 227 received placebo.
    • The primary safety measure was the occurrence of bleeding in the brain (symptomatic intracranial hemorrhage) within 36 hours of receiving one of the two blood thinners. Safety measures were analyzed by the study’s DSMB after every 30 patients were enrolled.

    Medical professionals providing care were aware of whether a blood thinner or placebo were given to each patient. However, neither the patients nor the professionals rating patient outcomes were aware of which patients in any group had received a blood thinner or placebo.

    “In addition, we were not able to address the possible benefit of giving these or similar blood thinners directly into an artery in the area of the stroke, rather than giving the medications systemically through a vein, as done in this trial,” Adeoye said.

    For patients undergoing thrombectomy (mechanical removal of a stroke-causing clot), studies are underway to determine whether delivering blood thinners into the affected artery may improve outcomes.

    The study was conducted at National Institutes of Health StrokeNet sites. StrokeNet was created to conduct small and large clinical trials and research studies to advance acute stroke treatment, stroke prevention and recovery and rehabilitation after a stroke across the lifespan. Other principal investigators were Andrew D. Barreto, M.D., M.S.; Joseph P. Broderick, M.D.; Colin P. Derdeyn, M.D.; Jordan Elm, Ph.D.; and James C. Grotta, M.D. The full list of authors and their disclosures are listed in the abstract.

    All study authors reported funding from the National Institute of Neurological Disorders and Stroke, a division of the National Institutes of Health.

    Source:

    American Heart Association

    [ad_2]

    Source link