Contemporary Clinical Trials Communications

Frailty is a state of increased vulnerability resulting from aging due to cumulative decline in physiological system over a lifespan. Few pharmacological agents have been investigated for the treatment of frailty. In Ayurveda, Ashwagandha (Withania Somnifera) is a popular botanical medicine used for improvement in physical strength and mental stress and has a potential for treatment of frailty. This placebo-controlled study assessed the efficacy and safety of a capsule containing 300mg of Ashwagandha Root Extract (ARE) administered twice daily orally for 8 weeks. Fifty elderly subjects with a frailty score [&ge;]7 based on Frailty Assessment and Screening Tool (FAST) were randomized in a 1:1 ratio to receive either Ashwagandha (ARE, n=25) or placebo (PL, n=25). Improvement in frailty after 8 weeks was assessed by FAST, 6-minute Walk Test (6MWT), Pittsburgh Sleep Quality Index (PSQI), Mini-Mental State Examination (MMSE) and Short Form Survey (SF-12) scores. Blood samples were collected at baseline and week 8 for estimation of C-Reactive Protein (CRP), cortisol and Creatinine Kinase (CK). Significant improvement (p<0.01) in scores for FAST, 6MWTs, PSQI, MMSE, and SF-12 were seen with ARE after 8 weeks. Also, significant improvements (p<0.05) were observed in CK and in CRP with ARE. These improvements were greater (p<0.05) with ARE as compared to placebo. ARE was well tolerated with no adverse effects, and no changes in hepatic and renal parameters. Thus, Ashwagandha root extract can be a valuable therapeutic option for improvement of health condition in frailty.

BackgroundCoronary heart disease(CHD) is a common disease of the cardiovascular system. Percutaneous coronary intervention(PCI) has been proven an effective treatment. Various complications after PCI may further affect the long-term efficacy of PCI. Previous trials have showed that both kinesitherapy(KT) and acupuncture are beneficial to patients with CHD, but need further confirmation. Acupuncture kinesitherapy(AKT) is a kind of combination therapy of acupuncture with exercise training. In this study, we plan to conduct a randomized controlled trial(RCT) to confirm the superior efficacy of AKT compared to KT and conventional medical therapy(MT) in post-PCI rehabilitation for CHD patients, and to further guide the clinical strategy. MethodsThis is a single-center randomized controlled trial with 3 parallel arms. We will recruit 102 CHD patients after PCI and randomly assign them to 3 groups. Participants in 3 groups will receive 2-week MT. Besides, participants in AKT and KT groups will also receive acupuncture kinesitherapy and kinesitherapy alone, respectively. They will be treated once a day, 5-day a week, and the treatment course will last for a total of 2-week with a 2-day off during the course. The primary outcome is the changes in cardiac function. The secondary outcomes include aerobic capacity, muscle strength, flexibility, balance, coordination, mental status, and activity of daily living. All outcomes will be measured at baseline and 2-week after treatment. Adverse events also will be recorded. The cardiac function and activities of daily living will be followed up at 1, 3 and 6 months after treatment. DiscussionWe expect findings of trial will provide important insight into application of AKT as a safety and more effective method for CHD patients. Successful completion of this proposed study will also contribute to promotion of AKT in the clinic in the future. Trial registrationChinese clinical trial registry (Register Number: ChiCTR2100048960) http://www.chictr.org.cn/index.aspx.

BackgroundUrolithin A, a stimulator of mitophagy, has been proposed as a therapy to improve skeletal muscle function via its beneficial effect on mitochondrial health. We aimed to systematically review existing evidence of the effect of urolithin A on measures of muscle strength, muscle mass and physical performance in humans. MethodsWe conducted a systematic review according to a prespecified protocol. Databases (PubMed, EMBASE, CINAHL, Scopus, ISRCTN.com and Clinicaltrials.gov) were searched from inception to 31st May 2025, with hits screened by two reviewers. We included randomised controlled trials comparing urolithin A to placebo or usual care. We sought outcomes measuring muscle strength, muscle mass or physical performance. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Results were grouped by outcome type and where applicable pooled using random-effects meta-analysis. ResultsWe identified 194 titles, of which three studies were eligible for inclusion. Included studies recruited 174 participants, and mean age ranged from 24 to 72 years. All studies were placebo controlled and examined doses of 500mg/d or 1000mg/d of Urolithin A. Overall risk of bias of included studies was low; urolithin was well tolerated with good adherence to therapy. Four of 12 included outcome measures showed a statistically significant positive effect of urolithin A on muscle strength and physical performance, with a further seven outcomes demonstrating non-significant improvements in muscle strength or physical performance. Pooled analysis of six-minute walk distance from two trials showed a non-significant improvement in walk distance with urolithin A (23m [95% CI -6m to 52m, p=0.12, I2=0%]). One study measured muscle mass but found no improvement in mass with urolithin supplementation. ConclusionsInsufficient evidence exists to support the use of urolithin A to improve muscle function in any population at present, but existing data support conducting larger randomised controlled trials in a range of target populations.

Creatine transporter (CTD) and guanidinoacetate methyltransferase (GAMT) deficiencies are rare inborn errors of creatine metabolism, resulting in cerebral creatine deficiency. Patients commonly exhibit intellectual and developmental disabilities, often accompanied by behavior problems, delayed speech, seizures, and motor impairments. There is currently no efficacious treatment for CTD, while the current management for GAMT requires lifelong treatment with a protein restricted diet and intake of high amounts of oral supplements. Efforts to develop effective, sustainable treatments for these disorders are limited by the lack of clinical and patient-derived meaningful outcomes. A core outcome set (COS) can facilitate consensus about outcomes for inclusion in studies. Unfortunately, patient and caregiver perspectives have historically been overlooked in the COS development process, thus limiting their input into the outcome selection. We partnered with caregivers and health professionals to establish the first COS for CTD and GAMT. The COS developed includes seven outcomes ("Adaptive Functioning", "Cognitive Functioning", "Emotional Dysregulation", "MRS Brain Creatine", "Seizure/Convulsions", "Expressive Communication", and "Fine Motor Functions") for both CTD and GAMT, and an additional outcome for GAMT ("Serum/Plasma Guanidinoacetate") that are important to stakeholders and consequently should be considered for measurement in every clinical trial. Caregivers were valued partners throughout the COS development process, which increased community engagement and facilitated caregiver empowerment. We expect this COS will ensure a patient-centered approach for accelerating drug development for CTD and GAMT, make clinical trial results comparable, minimize bias in clinical trial outcome selection, and promote efficient use of resources. 1-sentence take home messageA core outcome set for creatine transporter (CTD) and guanidinoacetate methyltransferase (GAMT) deficiencies was created through a multiphase process in partnership with caregivers and health professionals.

IntroductionDementia contributes to the disease burden worldwide, and people with hypertension or type 2 diabetes are associated with an elevated risk of developing dementia. It is essential to prevent or delay cognitive decline in people at high risk within the community. Our trials aim to evaluate the effects of adaptive cognitive training on community-dwelling older adults with hypertension or type 2 diabetes but no dementia. Method and analysisTwo multicenter, double-blind, randomized, placebo-controlled trials, named COgNitive Training in community-dwelling older adults at high risk for demENTia and with Hypertension (CONTENT-Hypertension) and COgNitive Training in community-dwelling older adults at high risk for demENTia and with Diabetes (CONTENT-Diabetes), will be conducted to investigate the effects of adaptive cognitive training on participants aged 60 years or above who have been diagnosed with hypertension or type 2 diabetes but no dementia. Each trial will enroll 120 participants. Participants will be recruited from local community in Shijingshan and Haidian District, Beijing, and allocated to either the intervention or control group using a 1:1 ratio. The intervention group will engage in 12 weeks of adaptive cognitive training, while the control group will receive 12 weeks of placebo cognitive training. A 24-week follow-up assessment will be conducted for all participants to evaluate the persistency of the effects. The primary outcome is the 12-week change in Montreal Cognitive Assessment (MoCA) Basic scores from baseline to the end of the intervention (12 weeks). Secondary outcomes include 6-week and 24-week changes in the MoCA from baseline; 6-week, 12-week, and 24-week changes in Trail Making Test-A&B (TMT-A, TMT-B), Digit Symbol Substitution Test (DSST), the World Health Organization/University of California at Los Angeles Auditory Verbal Learning Test (WHO-UCLA AVLT), and Boston naming test (BNT) scores of cognitive functions; 6-week and 12-week changes in Geriatric Depression Scale (GDS), Generalized Anxiety Disorder-7 (GAD-7), Pittsburgh sleep quality index (PSQI); and 12-week change in blood pressure (CONTENT-Hypertension) or fasting blood glucose and HbA1c (CONTENT-Diabetes) from baseline. Ethics and disseminationThis study will adhere to the ethical principles outlined in the Declaration of Helsinki and comply with international standards for Good Clinical Practice (GCP). All participants will sign the informed consent at baseline. This study has been approved by the Ethics Committee of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (approval numbers: 2023-139 and 2024-162). The findings of the trials will be disseminated through publications in peer-reviewed scientific journals and presented at academic conferences. Trial registration numbersNCT06512922 and NCT06524388. STRENGTHS AND LIMITATIONS OF THIS STUDYO_LIBoth trials are double-blind, randomized, placebo-controlled trials to investigate the effects of adaptive cognitive training among patients with hypertension or type 2 diabetes but no dementia. The rigorous randomized control trial design can ensure the reliability and efficacy of the trial. C_LIO_LIAdaptive cognitive training will automatically target the most impaired cognitive domains (domain-adaptive). The difficulty of cognitive training tasks will upgrade to the next level once the participants reach a high accuracy of 80% (difficulty-adaptive), which enables targeted and efficient training. C_LIO_LIThe use of placebo cognitive training can reduce the impact of the placebo effect on the results. C_LIO_LIAll training will be conducted remotely, allowing participants to complete the program from their homes to increase convenience and participant compliance. C_LI

Cancer-related fatigue (CRF) is a common and burdensome, often long term side effect of cancer and its treatment. Many non-pharmacological treatments have been investigated as possible CRF therapies, including exercise, nutrition, health/psycho-education, and mind-body therapies. However, studies directly comparing the efficacy of these treatments are lacking. To fill this gap, we conducted a parallel single blind randomized control trial with women with CRF to directly compare the effects of Qigong (a form of mind-body intervention) (n=11) to an intervention that combined strength and aerobic exercise, plant-based nutrition and health/psycho-education (n=13). This design was chosen to determine the comparative efficacy of two non-pharmacologic interventions, with different physical demand intensity, in reducing the primary outcome measure of self-reported fatigue (FACIT Additional Concerns subscale). Both interventions showed a mean fatigue improvement of more than double the pre-established minimal clinically important difference of three (Qigong: 7.068 +/- 10.30, Exercise/Nutrition: 8.846 +/- 12.001). Mixed effects ANOVA analysis of group x time interactions revealed a significant main effect of time, such that both groups significantly improved fatigue from pre- to post treatment (F(1,22)=11.898, p=.002, generalized eta squared effect size=.116) There was no significant difference between fatigue improvement between groups (independent samples t-test: p=.70), suggesting a potential equivalence or non-inferiority of interventions, which we could not definitively establish due to our small sample size. This study provides evidence from a small sample that Qigong improves fatigue similarly to standard exercise-nutrition. Qigong additionally significantly improved secondary measures of mood, emotion regulation, and stress, while exercise/nutrition significantly improved secondary measures of sleep/fatigue. These findings provide preliminary evidence for divergent mechanisms of fatigue improvement across interventions, with Qigong providing a gentler and lower-intensity alternative to exercise/nutrition. This clinical trial was registered with clinicaltrials.gov.

PurposeThe primary objective was to investigate the feasibility of a synchronous, online delivered, group-based, supervised, exercise oncology maintenance program supported with health coaching. MethodsAll participants had previously completed a 12-week group-based exercise study. In the current study, participants were randomized to a 12-week exercise oncology maintenance class with or without health coaching. The primary outcome was feasibility, assessed as intervention attendance, safety and fidelity, study recruitment, attrition and outcome assessment completion. Additionally, semi-structured interviews at the end of the intervention provided participants perspectives on intervention feasibility. ResultsForty participants (n8WK=25; n12WK=15) enrolled in the study. Feasibility was confirmed for recruitment rate (42.6%), attrition rate (2.5%), safety (no adverse events), health coaching attendance (97%), health coaching fidelity (96.7%), class attendance (91.2%), class fidelity (92.6%), and assessment completion (questionnaire=98.8%; physical functioning=97.5%). Based on the qualitative feedback, feasibility was facilitated by the convenience, while the diminished ability to connect with other participants online was a drawback compared to in-person delivery. ConclusionThe synchronous online delivery of an exercise oncology maintenance class, the additional health coaching support, and the tools used to measure the intervention effectiveness were feasible for individuals living with and beyond cancer.

Exercise can boost physical and cognitive health in older adults. However, there are a lack of accessible exercise programs that foster adherence among older adults. In this study, we aimed to establish the safety and feasibility of APEX, a new exercise program designed to optimize fitness and cognitive gains for older adults, in addition to evaluating its acute physiological effects, and assessing its possible effects on functional fitness and cognition among healthy older adults. APEX utilizes a multimodal progressive high-intensity interval training (HIIT) design, with high-intensity intervals focused on enhancing cardiovascular fitness and muscle strength, and recovery intervals that incorporate balance and mobility exercises. The APEX training was tested in healthy older adults (n=4) over the course of four weeks. Ultimately, APEX was found to be safe and feasible, with no adverse events and high adherence. Participants met heart rate targets for all of the high-intensity exercises, and all intervals had a significant difference in heart rates between high-intensity and recovery periods in linear effects models (p<0.001). Improvements in functional fitness were observed in aerobic endurance, lower body strength, and balance. The intervention was also associated with positive trends in the cognitive domains of information processing, working memory, executive control, and attention. APEX offers a promising alternative to traditional cardiovascular exercise modalities for older adults with additional benefits for functional fitness and cognition. These results encourage further testing of the APEX program in older adults and different clinical populations.

BackgroundAn increasing number of acupuncture clinical trials are registered, but the reports of results and data transparency are unclear. We aim to analyze and evaluate the current state of registration and reports of acupuncture clinical trials. MethodsThis paper focused on the acupuncture clinical trials that met the criteria in relevant studies registered and published during the period between 1 Jan 2013 to 31 Dec 2021. We traced by email to leaders that the report could not be searched. Besides, questionnaire investigation was chosen to acupuncture clinicians around by WeChat. ResultsThe overall reporting rate of acupuncture clinical trial results from the two registration centers was 25%. Clinicaltrials.gov reporting rate was 12% and that from ChiCTR was 41%. Only a small proportion of trials were available on the registry website. Only the NIH clinical registry platform has records on the status of studies. We only received 3 replies that indicated the project was due to be ended but not completed. According to questionnaire, 157 clinicians have led clinical projects in Acupuncture. It shows that 84% projects were ended but not completed or not completed by the due date. About the reasons that caused the failure to find articles after the end of the project, 85% participants thought projects were ended but not completed or not completed by the due date. 15% participants thought projects were manuscript rejected, manuscript accepted but not in print, results protected, registration number unmarked, project delayed or negative results not submitted. ConclusionThe number of acupuncture clinical trial registrations is steadily increasing, but the reporting rate of trial results is relatively low and the transparency of data is not ideal. Therefore, first of all, researchers should put more attention on trials designed, trial reported and respect to science. Secondly, set up a research progress tracker on registration platforms accessible to the public users. At the same time, the journal is suggested that adjust the evaluation criteria for reporting the negative results. Researchers with negative results are encouraged to show. Most importantly, the funders are recommended to optimize the ended review.

A key driver that leads to age-associated decline and chronic disease is mitochondrial dysfunction. Our prior work revealed strong community interest in the concept of mitochondrial fitness that led to development of a video based science communication intervention to prompt behavior change in adults aged 50+. AimTo conduct formative and summative evaluations of MitoFit, an instructional, biologically based communication intervention aimed at improving physical activity (PA) in older adults, aged 50+. MethodsPhase 1 formative evaluation- Community-dwelling older adults (N=101), rated the acceptability, appropriateness and helpfulness of our MitoFit video series, titled, "How to Slow Down Aging Through Mitochondrial Fitness." ([&ge;] 4 out of five on a Likert-scale survey). Phase II summative evaluation- A subgroup of phase I participants (N=19) participated in a 1-month MitoFit intervention prototype to evaluate intervention and data collection feasibility ([&ge;] 70% completion). ResultsPhase I: Participants (mean age: 67.8 [SD 8.9]; 75% female) rated the MitoFit videos as acceptable (agree: 97%-100%), appropriate (agree: 100%) and helpful (agree: 95%-100%) to support adaptation and continued work on our novel approach. Phase II: Participants (mean age: 71.4 [SD 7.9]; 72% female) demonstrated MitoFit competencies (obtaining pulse, calculating maximum and zone 2 heart rate, demonstration of exercises). At one-month post-instruction, 13 participants (68.4%) had completed a self-initiated daily walking/exercise plan and submitted a daily activity log. Feasibility scores ranged from 89.4% to 94.7%. Fifteen participants (78.9%) stated an intention to continue the MitoFit intervention. ConclusionMitoFit was enthusiastically embraced, and is a cost-effective, scalable, and efficacious intervention to advance with community-dwelling older adults.

ObjectivesEstablish clinical evidence regarding acupuncture combined with statin for blood lipid control in patients with angina pectoris (AP) of coronary heart disease (CHD) by systematically analyzing data from all available studies. DesignA systematic review and meta-analysis. Data sourcesThe literature search involved eight databases (China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang, VIP Database for Chinese Technical Periodicals, PubMed, Embase, Web of Science, and Cochrane Library) and was finished on February 1, 2024. Eligibility criteriaRandom controlled trials (RCTs) investigating the efficacy of acupuncture combined with statin on lipid levels in patients with AP of CHD were eligible. The outcomes assessed were the lipid metabolism indicators, including TC, TG, LDL-C, and HDL-C, as well as the safety of the treatment. Data extraction and synthesisData extraction and quality evaluation were conducted by two independent reviewers, with any discrepancies discussed by a third researcher. Pooled mean differences (MD) with 95% confidence intervals (CIs) were calculated for each outcome. Sensitivity and subgroup analyses were carried out to explore the heterogeneity. Publication bias was assessed using a funnel plot. The quality of the evidence was evaluated using the GRADE system. ResultsThe final meta-analysis included nine eligible studies involving 754 patients. When comparing statin group, the acupuncture plus statin group showed lower levels of TC (MD=-0.48, 95% CI: -0.61 to -0.35, P<0.00001), TG (MD=-0.59, 95% CI: -0.86 to -0.32, P<0.00001), LDL-C (MD=-0.66, 95% CI: -0.99 to -0.33, P=0.0001), and higher levels of HDL-C (MD=0.16, 95% CI: 0.06 to 0.26, P=0.001). Each study included in the analysis exhibited some degree of bias. Significant publication bias was detected for the primary outcomes. Evidence quality for the primary outcomes was graded as very low. ConclusionsAcupuncture as an adjunctive treatment can further improve lipid profile in individuals diagnosed with AP of CHD based on statin therapy. However, the clinical significance of this effect remains unclear; it is necessary to confirm the findings through more high-quality RCTs in the future. Trial registration numberPROSPERO CRD42023465292. STRENGTHS AND LIMITATIONS OF THIS STUDYO_LIThis comprehensive systematic review will collect data regarding the combined therapy (acupuncture + statin) on lipid profiles in patients with AP of CHD to provide new evidence supporting the use of acupuncture treatment for AP of CHD. C_LIO_LISubgroup analysis based on the duration of intervention and types of acupuncture will provide a more detailed evaluation of the effectiveness of the combined therapy. C_LIO_LIA thorough evaluation of the quality of the evidence for the primary outcomes was conducted using the Grading of Recommendation Assessment, Development, and Evaluations (GRADE) system. C_LIO_LIThis review has limited ability to draw clear conclusions due to poor quality of evidence. C_LIO_LIWe restricted the literature search to eight electronic databases and ignored a search for gray literature, which may miss important literature and could introduce publication bias. C_LI

ObjectivesThis study explored the feasibility and preliminary efficacy of a music-based, multicomponent exercise intervention among community-dwelling older adults with mild-to-moderate cognitive impairment. Methods13 older adults aged 85{+/-}9 years with mild-to-moderate cognitive impairment completed multicomponent exercise training for 20 weeks at an independent living facility. Participants received aerobic, resistance, and balance training paired with beat-accentuated music stimulation (BMS). Participants adherence to the training was tracked down and their cognitive and physical functioning and quality of life were assessed at pre- and post-test. Results13 participants attended an average of 4.6 days/week over 20 weeks and reported high satisfaction with the intervention (90.6%). Participants showed significant improvement in global cognition, cognitive processing speed, and walking endurance/aerobic fitness at post-test. ConclusionsThese findings support the feasibility of music-based, multicomponent exercise training for older adults in an independent living facility and set the stage for future studies to test the efficacy of music on physical activity and ensuing health outcomes. Clinical ImplicationsMusic-based, multicomponent exercise training can be beneficial for community-dwelling older adults with mild-to-moderate cognitive decline. BMS can be combined with exercise training to manipulate exercise tempo and may provide a source of motivation to help older adults adhere to exercise.

IntroductionNeutrophilia and high levels of proinflammatory cytokines and other mediators of inflammation are common finds in patients with severe acute respiratory syndrome due to COVID-19. By its action on leukocytes, we propose colchicine as an intervention worthy of being tested. ObjectiveTo evaluate whether the addition of colchicine to standard treatment for COVID-19 results in better outcomes. MethodsWe present the interim analysis of a single-center randomized, double-blinded, placebo controlled clinical trial of colchicine for the treatment of moderate to severe COVID-19, with 38 patients allocated 1:1 from April 11 to July 06, 2020. Colchicine regimen was 0.5 mg thrice daily for 5 days, then 0.5 mg twice daily for 5 days. The first dose was 1.0 mg whether body weight was [&ge;] 80 kg. EndpointsThe primary endpoints were the need for supplemental oxygen; time of hospitalization; need for admission and length of stay in intensive care units; and death rate and causes of mortality. As secondary endpoints, we assessed: serum C-reactive protein, serum Lactate dehydrogenase and relation neutrophil to lymphocyte of peripheral blood samples from day zero to day 7; the number, type, and severity of adverse events; frequency of interruption of the study protocol due to adverse events; and frequency of QT interval above 450 ms. ResultsThirty-five patients (18 for Placebo and 17 for Colchicine) completed the study. Both groups were comparable in terms of demographic, clinical and laboratory data at baseline. Median (and interquartile range) time of need for supplemental oxygen was 3.0 (1.5-6.5) days for the Colchicine group and 7.0 (3.0-8.5) days for Placebo group (p = 0.02). Median (IQR) time of hospitalization was 6.0 (4.0-8.5) days for the Colchicine group and 8.5 (5.5-11.0) days for Placebo group (p = 0.03). At day 2, 53% vs 83% of patients maintained the need for supplemental oxygen, while at day 7 the values were 6% vs 39%, in the Colchicine and Placebo groups, respectively (log rank; p = 0.01). Hospitalization was maintained for 53% vs 78% of patients at day 5 and 6% vs 17% at day 10, for the Colchicine and Placebo groups, respectively (log rank; p = 0.01). One patient per group needed admission to ICU. No recruited patient died. At day 4, patients of Colchicine group presented significant reduction of serum C-reactive protein compared to baseline (p < 0.001). The majority of adverse events were mild and did not lead to patient withdrawal. Diarrhea was more frequent in the Colchicine group (p = 0.17). Cardiac adverse events were absent. DiscussionThe use of colchicine reduced the length of supplemental oxygen therapy and the length of hospitalization. Clinical improvement was in parallel with a reduction on serum levels of C-reactive protein. The drug was safe and well tolerated. Colchicine may be considered a beneficial and not expensive option for COVID-19 treatment. Clinical trials with larger numbers of patients should be conducted to further evaluate the efficacy and safety of colchicine as an adjunctive therapy for hospitalized patients with moderate to severe COVID-19.

Iodine has strong antimicrobial properties and has been used in topical applications as antiseptic. Its systemic use in form of iodine complexes derived from dried seaweed extract is beneficial in treating various disorders. Hepatitis C Virus (HCV) chronic infection is present in 6-10% of the Pakistani population and is a major healthcare burden that could benefit from innovative therapeutic regimens. ObjectiveA pilot study has shown the safety and efficacy of iodine complexes in chronic Hepatitis C virus infection. and this clinical study is aimed to further explore the previous findings. MethodsThis is an open-labeled, active-controlled, three-arm, parallel-group study including 90 patients of chronic HCV infection with each arm having 30 patients. The patient groups received 15mg/day iodine complex only, the standard of care therapy interferon+ribavirin, and iodine complex in combination with interferon+ribavirin regimen for 6 months. Efficacy assessment will base upon post-treatment Rapid Virological Response (RVR) at 4 weeks, Early Virological Response (EVR) at 12 weeks, and End of Treatment Viral Response (ETR) at 24/48 weeks. ResultsAs only 3.33% of patients showed at the ETR with iodine complex alone, combination with interferon+ribavirin showed significant improvement in comparison to interferon+ribavirin alone. Iodine complex+ interferon+ribavirin showed 80% RVR and 90% ETR while the standard of care therapy showed 66.7% RVR and 76.67% ETR, respectively. No additional adverse events of iodine complex were observed. ConclusionIodine complex showed a significant synergistic effect when combined interferon+ribavirin regimen and could be useful in relapsers and non-responders.

IntroductionSarcopenia is the age-related loss of muscle mass and strength. It is associated with significant adverse personal and health-economic outcomes. Despite advances in understanding the biology of muscle ageing, effective treatments remain limited. Exercise is currently the only proven intervention, but many older people are unable or unwilling to sustain the intensity of exercise required to gain results. Consequently, there is a major unmet need for new therapies. REVITALiSE is an early-phase experimental medicine platform trial designed to efficiently evaluate promising interventions in people with sarcopenia. By identifying and selecting the most promising interventions to progress to large randomised controlled trials, REVITALiSE aims to accelerate the development of effective therapies for this under-served population. Methods and analysisThe REVITALiSE platform comprises a series of parallel-group, individually randomised, controlled, open-label, proof-of-concept subtrials. Each subtrial will enrol 30 participants aged 65 years and older with probable sarcopenia, defined according to the European Working Group on Sarcopenia in Older People (EWGSOP) guidelines. The platform is designed to evaluate a range of interventions, including exercise-based approaches, device-based therapies, and nutraceuticals. Participants will be randomised in a 1:1 ratio to receive either the intervention or usual care. The primary outcome, analysed in a modified intention to treat (mITT) population, is the between-group difference in four-metre walking speed between baseline and 12-week follow-up. Secondary outcome measures specified in the master protocol include handgrip strength, the Short Physical Performance Battery (SPPB), and lean muscle mass (assessed by Dual X-ray absorptiometry). Muscle biopsies of the vastus lateralis will also be taken at baseline and follow-up. Additional mechanistic outcomes will be determined by the proposed mode of action of each intervention and specified in the relevant subtrial annex. Adverse events will be recorded for the duration of the trial. Ethics and disseminationUK Health Research Authority and Northeast - Tyne and Wear South Research Ethics Committee (IRAS 352708). Results will be made available to participants, their families, patients with sarcopenia, the public, regional and national clinical teams, and the international scientific community. Trial registration number: ISRCTN10801475 Protocol V1.0 08 May 2025 Sponsor: Newcastle Upon Tyne NHS Foundation Trust REC: NE Tyne and Wear South NHS Research Ethics Committee ref: (IRAS 352708; ref: 25/NE/0115)

The poor reporting quality of methods and outcomes is relatively recognized in the biomedical field. Its prevalence and implications have been studied in the cardiovascular rehabilitation literature but not so extensively in exercise-based trials. Our main objective was to cross-sectionally estimate the prevalence of both methodological and outcome reporting items in CVR trials with EBI. We also searched for associations (secondary outcomes) between (1) the effect size reported and the direction of the primary outcome, as well as (2) associations with the frequency of Spin. We cross-sectionally screened the sample of eligible trials dated between 2017 and 2021, and then collected the prevalence of methodological and outcome characteristics, independent and blinded manner. Our study shows that there was an insufficient reporting of methods and outcomes. Also, studies reporting effect size measures had a lower chance of Spin. The primary outcome effect size was not reported in 35% of the studies SES. However, more than 2/3 of the sample (69%) had a statement in the discussion or conclusion sections mentioning clinical relevance or meaningful benefit of the statistically significant results. Selective outcome reporting has important implications for translating science into practice, once not so threatens the validity of an intervention effectiveness, but also frustrates the use of its evidence in meta-analyses. What is new?O_LIOur study shows that randomized controlled trials with cardiovascular rehabilitation based on exercise insufficiently reported the various methods and outcomes characteristics. C_LIO_LIAlthough nearly 70% studies had stated its outcomes as clinically meaningful within our sample, about 41%of the studies clearly stated the primary outcome confidence intervals. C_LIO_LIMore than half of the sample presented at least one spin in the results section, and studies reporting effect size measures had a lower chance of Spin. C_LIO_LI40% of the studies within our sample did not report a priori sample size calculation, with 1/4 not stating the number of randomized subjects that could meet the intended power. C_LIO_LIWe did not find any associations regarding the direction of the results (positive or negative) and the prevalence of spin, contrary to what have been found in the literature. C_LI

BackgroundIrregular bowel habits including constipation are common gastrointestinal issues, significantly impacting quality of life. While conventional pharmacological treatments exist, they often come with side effects and offer limited long-term relief, driving interest towards safer, effective herbal alternatives. Cassia fistula (C. fistula) has long been recognized for its laxative properties and has been reported to be a safer alternative to Senna (Cassia angustifolia). PurposeThis study aimed to evaluate the efficacy and safety of a standardized extract of C. fistula compared to Senna extract in healthy individuals experiencing irregular bowel habits. MethodsA two-arm, open-label, randomized, multicentric, interventional, prospective clinical study was conducted in India with 70 participants (35 per group). One group received the standardized C. fistula extract and the other group received Senna extract for 14 days, followed by a 7-day post-consumption follow-up. Primary outcomes included changes in bowel movement frequency. Secondary outcomes assessed stool consistency (Bristol Stool Form Scale), straining, bowel satisfaction after defecation, anorectal blockage, use of manual manoeuvres, average time spent on defecation, time to first bowel evacuation post intervention and associated clinical symptoms (headache, belching, flatulence, abdominal distension, acidity). Safety was evaluated through vitals, laboratory parameters, and adverse events. ResultsC. fistula extract significantly increased bowel movement frequency (3.30 {+/-} 0.92 to 5.90 {+/-} 1.24 at Day 14, p<0.05) and improved stool consistency comparable to Senna extract. Straining and bowel satisfaction after defecation also significantly improved with the use of C. Fistula. Notably, C. fistula extract showed significantly greater reduction in the sensation of anorectal blockage at Days 14 and 21 (p<0.05) and a faster onset of action (shorter time to first defecation) compared to Senna. Associated symptoms of constipation also reduced significantly. C. fistula extract was better well-tolerated, with fewer product-related adverse events compared to Senna. ConclusionC. fistula extract was found to be effective in irregular bowel habits, offering comparable efficacy to Senna while proving to be superior in reducing the sensation of anorectal blockage and achieving a faster time to first bowel evacuation. It also demonstrated a more favorable safety profile with significantly fewer product-related adverse events. Therefore, C. fistula extract represents a promising non-habit-forming herbal alternative for bowel regulation.

IntroductionSarcopenia is characterized by the progressive weakening of muscle function that occurs with age. This condition frequently leads to frailty, disability, and even death. Research on sarcopenia prevention is growing. Tele-exercise intervention is increasingly gaining attention in this field, with the rapid advancement of the Internet and the influence of the COVID-19. However, there is a lack of empirical support for its effectiveness. Our study aims to assess the effect of tele-exercise on sarcopenia in older persons, specifically focusing on its ability to improve muscle strength, muscle mass and physical performance. Methods and analysisSearching will be performed in the following eleven databases (Medline, Embase, Cochrane Central Register of Controlled Trials, CINAHL, PsycINFO, WOS, Scopus, CBM, CNKI, WANFANG, VIP) for published trials and two trial registries (Clinicaltrials.gov and the WHO International Clinical Trials Registry Platform) for unpublished trials. Google Scholar will be utilized to find grey literatures. The criterion of inclusion will be clinical trials involving tele-exercise interventions in older adults ([&ge;] 60y) diagnosed with sarcopenia (possible, confirmed, or severe sarcopenia). For data synthesis, we will utilize a summary table to show the major characteristics of selected trials and a summary graph to demonstrate the risk of bias using RoB 2 in each trial, which will be further discussed in a narrative synthesis. The possibility of meta-analysis for quantitative data will be assessed according to the homogeneity analysis of the trials, using the methods of fixed or random effects model. If meta-analysis is possible, subgroup analysis and sensitivity analysis will be performed as well. Publication bias will be assessed through the use of the funnel plot and Eggers linear regression test when an adequate number of trials are available. Finally, the GRADE approach will be used to classify the certainty of evidence body into four categories (high, moderate, low, and very low). Ethics and disseminationThe findings of the systematic review will be shared through publishing in a peer-reviewed journal and presentation at appropriate conferences. Since we will not be utilizing specific patient data, ethical approval is unnecessary. PROSPERO registration numberCRD42024516930 Strengths and limitations of this study- This will be the first systematic review on tele-exercise for sarcopenia prevention in older adults. - This review will seek to determine the duration, frequency, intensity and type of tele-exercise that is most appropriate for preventing and treating sarcopenia. - The results may fill the gap pertaining to accurate tele-exercise prescription in older adults with sarcopenia. - This review will adhere to the PRISMA standards for conducting and reporting systematic reviews and meta-analyses in order to reduce bias. - High heterogeneity may exist due to the different diagnostic criteria and thresholds for sarcopenia.

AbstractO_ST_ABSBackgroundC_ST_ABSIn an open label pilot study dried bilberries were effective in inducing clinical, endoscopic and biochemical improvement in ulcerative colitis (UC) patients. Aim was the investigation of efficacy of anthocyanin rich extract (ACRE), the presumptive active ingredient of bilberries, in a controlled clinical trial in moderate-severe UC. MethodsWe performed a multicenter randomized, placebo-controlled, double-blind study (planned initially for 100 patients; premature termination due to COVID-19 pandemic). Patients had moderate-severe active UC at screening (Mayo-score 6-12, endoscopic sub-score at least 2) and were randomized at baseline (verum: placebo, 2:1). Continuation of all UC-directed stable medical therapy was allowed. Primary endpoint was clinical response at week 8 (reduction of total Mayo-score at least 3 points). Biochemical (fecal calprotectin) and centrally-read endoscopic response were amongst the secondary endpoints. ResultsOut of 48 patients screened in six Swiss trial centers, 34 were randomized. Eighteen ACRE and eight placebo patients could be analyzed in the Per-Protocol-Set. Half (9/18) of ACRE patients and 3/8 of placebo patients revealed clinical response at week 8 (CI 0.399-6.963; p=0.278). An improvement of the Mayo-score was observed in 77.8% of ACRE treated patients (62.5% of placebo). Fecal calprotectin dropped from 1049+/-1139 to 557+/-756g/g feces in the ACRE but not in the placebo group (947+/-1039 to 1040+/-1179; p=0.035). Adverse events were rare. ConclusionsACRE therapy was not significantly superior to placebo at inducing a clinical response. However, placebo response was unusual high. Moreover, there was a significant calprotectin decrease at end of treatment, indicative of ACRE biochemical efficacy in UC. Study HighlightsO_ST_ABSWhat is knownC_ST_ABSO_LIDried bilberries have been reported to ameliorate active ulcerative colitis (UC) in an uncontrolled pilot trial C_LIO_LIAnthocyanins (flavonoids) are regarded to be the active anti-inflammatory compound of bilberries C_LIO_LIAn anthocyanin rich extract (ACRE) of bilberries was reported to ameliorate colitis in mouse models C_LI What is new hereO_LIIn a multi-center randomized, double-blind, placebo controlled, parallel group study in patients with moderate to severe active UC, ACRE did not reach the statistical endpoint of clinical response C_LIO_LIAn unusually high placebo response was observed C_LIO_LIACRE induced significant biochemical response with significant decrease in calprotectin levels C_LI

ObjectivePhysiotherapists are supposed to have a great impact on the body awareness of their clients through passive and active measures. The aim of this study was to investigate the effect of a single session of manual massage or exercise on body awareness. MethodsA three-arm randomized controlled study including 96 healthy volunteers (18 - 65 years) was conducted at the Institute of Physical Medicine & Rehabilitation, at the Kepler University Hospital in Linz/Austria. Anonymous questionnaire assessments and analysis with intention-to-treat approach were performed. Participants were assigned to a single intervention of massage (full-body massage with slow strokes and gentle kneading), exercise (moderate body workout, video-based exercise instructions) or lecture on medicinal herbs (video-based lecture, control group). Primary endpoints were the changes of body awareness recorded with the non-verbal Awareness Body Chart test. Secondary endpoints were the changes of body awareness scored with a German body awareness questionnaire (Kurzer Fragebogen zur Eigenwahrnehmung des Koerpers, KEKS) and changes in mood scored with a German questionnaire on mood (Befindlichkeitsfragebogen). ResultsThe Awareness Body Chart total score increased in both intervention groups but not in the control group with significant differences in the change between control group and both other groups (massage vs. control: +0.47, 95% CI 0.30 to 0.64; exercise vs. control: +0.31, 95% CI 0.15 to 0.45; massage vs. exercise: +0.19, 95% CI -0.02 to 0.34). An increase of the KEKS total score was found in the exercise in comparison to the control group. Mood significantly improved in both intervention groups compared to the control group. ConclusionsIn this study single session interventions of massage or exercise presented immediate positive impact on body awareness and furthermore on mood. The trial may serve as a prototype for further research on body awareness. Trial RegistrationRegistered in the clinicaltrials.gov database (NCT05004272)