Trials最新文献

{"title":"ReVita: home-based transcutaneous auricular vagus nerve stimulation for reducing pathological fatigue in chronic neurological and post-infectious conditions-study protocol for a randomized, double-blind, sham-controlled trial.","authors":"Anni Richter, Maria Kuehne, Margarita Darna, Tino Zaehle","doi":"10.1186/s13063-026-09919-6","DOIUrl":"10.1186/s13063-026-09919-6","url":null,"abstract":"<p><strong>Background: </strong>Pathological fatigue is one of the most prevalent and disabling symptoms across chronic neurological, post-infectious, and inflammatory diseases, yet effective treatments remain limited. Transcutaneous auricular vagus nerve stimulation (taVNS) is a safe, non-invasive neuromodulatory intervention that targets neuroimmune and autonomic pathways implicated in the development and persistence of fatigue. This randomized controlled trial investigates whether home-based taVNS can reduce fatigue severity in a transdiagnostic population.</p><p><strong>Methods: </strong>This study is a randomized, double-blind, sham-controlled, parallel-group clinical trial conducted at the University Hospital Magdeburg. Eligible adult participants (≥ 18 years) with clinically significant chronic fatigue from two diagnostic clusters (neurological disorders and post-infectious syndromes) will be enrolled and randomized (1:1) to receive either active taVNS or sham stimulation for 4 weeks. Stimulation is self-administered at home twice daily for 30 min. The primary outcome is change in fatigue severity from baseline to the end of the intervention, assessed using the Modified Fatigue Impact Scale (MFIS). Secondary outcomes include quality of life (WHOQOL-BREF), depressive symptoms (BDI-II), daytime sleepiness (ESS), cognitive performance (SDMT and TAP subtest alertness), neurophysiological markers (resting-state EEG and P50 sensory gating) and HRV indices (Garmin Vivosmart 5). Blinding integrity will be assessed at study end. Data will be analyzed according to an intention-to-treat framework. No interim analyses are planned. Adverse events will be monitored continuously.</p><p><strong>Discussion: </strong>This is to be the first transdiagnostic study to evaluate home-based taVNS as a potential therapeutic approach for pathological fatigue across multiple chronic disease groups. The combination of rigorous blinding, digital monitoring, and parallel assessment of clinical and physiological parameters allows for an in-depth evaluation of both treatment effectiveness and mechanistic correlates. If successful, taVNS could offer a scalable and accessible intervention for a large and underserved patient population.</p><p><strong>Trial registration: </strong>The trial was registered in the German Clinical Trials Register (DRKS) under the identification number DRKS00038292. Registered on December 01, 2025. URL: https://drks.de/search/de/trial/DRKS00038292 .</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"27 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of dexmedetomidine versus remimazolam protocolized sedation during lower limb nerve block on early stress response and quality of recovery in patients undergoing diabetic foot ulcer repair: a randomized controlled trial protocol.","authors":"Yawen Tang, Jiamin Hou, Shenggang Wu, He Liu, Ling Tong, Qin Zhang, Yonghe Hu, Haojie Gong","doi":"10.1186/s13063-026-09937-4","DOIUrl":"10.1186/s13063-026-09937-4","url":null,"abstract":"<p><strong>Background: </strong>For patients undergoing diabetic foot ulcer (DFU) repair, lower limb nerve block is the preferred anesthetic regimen. However, the block alone often fails to fully eliminate intraoperative anxiety and stress responses. Adjunctive procedural sedation and analgesia (PSA), using agents such as dexmedetomidine or remimazolam, is a key strategy to enhance surgical comfort. Nevertheless, the comparative effects of these two agents on early stress response and quality of recovery remain unclear.</p><p><strong>Methods: </strong>This is a prospective, randomized, single-center, single-blind, superiority controlled trial. A total of 160 patients aged 18 to 75 years undergoing elective DFU repair will be enrolled and randomized into Group A (dexmedetomidine) and Group B (remimazolam). The primary outcome is the change in serum cortisol levels from preoperative baseline to 2 h postoperatively. Secondary outcomes include the following: vital signs; postoperative pain intensity scores; intraoperative stress level; postoperative quality of recovery; and patient and surgeon satisfaction scores.</p><p><strong>Discussion: </strong>This study aims to compare the effects of dexmedetomidine and remimazolam PSA on attenuating stress hormone release and improving early postoperative quality of recovery in patients undergoing DFU repair. The future findings will provide high-quality clinical evidence for reducing perioperative stress levels, enhancing patient comfort, and accelerating postoperative recovery.</p><p><strong>Trial registration: </strong>Chinese Clinical Trial Registry ChiCTR2500113746. Registered on 2 December 2025.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"27 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Randomised, placebo-controlled study to assess the safety and efficacy of Enterosgel® in the treatment of functional abdominal pain in children and young people (ENTOPIC): study protocol for a clinical trial.","authors":"Carol A Howell, Manjula Velayudhan Nair, Marcus Karl-Heinz Auth, Christine Spray, Dharamveer Basude, Matthew Dodd, Elena Markaryan, Radovan Hnatič, Stephen J Allen","doi":"10.1186/s13063-026-09913-y","DOIUrl":"10.1186/s13063-026-09913-y","url":null,"abstract":"<p><strong>Background: </strong>Functional abdominal pain disorders (FAPDs) comprise of irritable bowel syndrome, functional dyspepsia, abdominal migraine and functional abdominal pain not otherwise specified. FAPDs are common in children worldwide, decrease health related quality of life, reduce attendance and participation in school and after-school activities similar to children with inflammatory bowel disease, and incur significant health care costs. The aetiology is thought to involve structural and/or functional disruptions in one or more elements of the microbiota-gut-brain axis. Several different treatment approaches are available, reflecting that none is proven to have significant efficacy. The medical device Enterosgel®, a silicon-based intestinal absorbent, adsorbs immune proteins, bacterial breakdown products and bile acids and normalises the intestinal microbiota. Enterosgel® is effective in irritable bowel syndrome with diarrhoea in adults and is available on prescription and over-the-counter. We plan to evaluate the efficacy, tolerability and safety of Enterosgel® in the treatment FAPDs in children and young people.</p><p><strong>Methods: </strong>In a UK two-centre, parallel arm, randomised, double-blind, placebo-controlled trial, we will recruit children aged 3-18 years diagnosed with a FAPD during a routine health facility assessment and in whom other significant gastrointestinal disorders have been excluded. After an initial 2-week observation phase, eligible children will be randomised 1:1 to receive Enterosgel® or a matching placebo drink twice daily for 4 weeks during the double-blind treatment phase, then all children will receive open-label Enterosgel® treatment for a further 4 weeks. With support from parents/carers, children will record abdominal pain daily using the Wong-Baker FACES Pain Rating Scale. The primary outcome is change in mean daily pain score during the initial observation phase and the double-blind phase in the Enterosgel® versus the placebo arm. Secondary outcomes include change in gastrointestinal symptoms (assessed PedsQL™ 3.0 GIS module) and quality of life (KIDSCREEN-27) recorded at baseline and 6 and 10 weeks. After the initial clinical assessment, all procedures will be conducted remotely with study interventions sent by post.</p><p><strong>Discussion: </strong>In the absence of a currently available effective treatment, this study will assess the acceptability, efficacy and safety of Enterosgel® in the treatment of children and young people with FAPDs.</p><p><strong>Trial registration: </strong>ISRCTN ISRCTN16474818. Registered on 21 May 2025, https://www.isrctn.com/ISRCTN16474818.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"27 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preoperative antibiotics for mild or moderate acute cholecystitis (POMMAC): study protocol for a non-inferiority, open-label, randomized controlled trial.","authors":"Petra Terho, Ville Sallinen, Hanna Lampela, Hanna Koppatz, Henna Sammalkorpi, Panu Mentula","doi":"10.1186/s13063-026-09917-8","DOIUrl":"10.1186/s13063-026-09917-8","url":null,"abstract":"<p><strong>Background: </strong>Evidence is lacking on the effect of preoperative antibiotic therapy on postoperative infections in acute cholecystitis. The POMMAC trial aims to investigate whether a single dose of antibiotic prophylaxis is non-inferior to continuous preoperative antibiotic therapy in terms of postoperative infections.</p><p><strong>Methods: </strong>This is a non-inferior, open-label randomized controlled trial aiming to include 456 participants. Eligible participants with mild or moderate acute cholecystitis will be randomized at a 1:1 ratio to receive either continuous or a single dose of preoperative antibiotic prophylaxis. The primary outcome is the rate of postoperative infections within 30 days postoperatively. Secondary outcomes are rates of conversion from laparoscopic to open cholecystectomy, other postoperative complications (Clavien-Dindo), a composite outcome incorporating antibiotic-related hypersensitivity reactions, Clostridium difficile diarrhea, and yeast infections within 30 days postoperatively, and the length of stay.</p><p><strong>Discussion: </strong>The POMMAC trial will provide evidence on the effect of preoperative antibiotic therapy on postoperative infections in acute cholecystitis. Abstaining from unnecessary preoperative antibiotic therapy could reduce antimicrobial resistance, adverse antibiotic-related events, and healthcare expenses.</p><p><strong>Trial registration: </strong>EU CTIS: https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2024-515958-24-00 protocol version 2.4. Registered on April 9th, 2025.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"27 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crystalloid vs colloid for Hemodynamics during Anesthesia INduction in TAVR patients (CHAIN-T): study protocol for a randomized controlled trial.","authors":"Xiaoshuang Tuo, Fahan Wang, Youjun Chen, Min Chen, Zhihong Lu","doi":"10.1186/s13063-026-09906-x","DOIUrl":"10.1186/s13063-026-09906-x","url":null,"abstract":"<p><strong>Objective: </strong>To assess whether preload with colloids could reduce hypotension during induction in patients undergoing transcatheter aortic valve replacement (TAVR) compared to crystalloids.</p><p><strong>Methods: </strong>This study is a single-center, prospective, randomized, double-blind, parallel-controlled trial conducted at Xijing Hospital. A total of 116 patients scheduled for elective TAVR under general anesthesia will be randomly assigned in a 1:1 ratio to either the colloid group or the crystalloid group, receiving either 5 ml/kg of colloid or crystalloid solution before anesthesia induction infused over 15 min. The primary outcome is the area under curve (AUC) of the change in mean arterial pressure (MAP) from baseline during the induction period (until 15 min after induction). Secondary outcomes include the incidence of intraoperative hemodynamic instability, the use of intraoperative vasoactive drugs, the Sequential Organ Failure Assessment (SOFA) score on the first postoperative day, postoperative hospital length of stay, the rate of intensive care unit (ICU) admission postoperatively, all-cause mortality during hospitalization and by 30 days after surgery, and the incidence of renal replacement therapy by 30 days after surgery.</p><p><strong>Discussion: </strong>The results of this study will provide evidence on optimizing fluid preload to prevent hypotension during induction, reduce postoperative complications, and enhance recovery for patients undergoing TAVR. The findings are expected to promote anesthesia protocols in this patient population.</p><p><strong>Trial registration: </strong>The study protocol and statistical analysis plan were approved by the institutional Ethics Committee of Xijing Hospital, Fourth Military Medical University (XJLL-KY-20252560). The study was registered in ClinicalTrials.gov (NCT07329660) on December 29, 2025.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"27 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The World Health Organization Antenatal CorTicosteroids for Improving Outcomes in preterm Newborns (ACTION-III) trial-rationale for the selected lower steroid dose.","authors":"","doi":"10.1186/s13063-026-09903-0","DOIUrl":"10.1186/s13063-026-09903-0","url":null,"abstract":"<p><p>Antenatal corticosteroids (ACS), most commonly administered as betamethasone or dexamethasone, remain a cornerstone of care for women at risk of preterm birth. However, the standard 24-mg regimen introduced more than five decades ago has not undergone formal dose-finding evaluation. Emerging concerns regarding possible dose-related adverse effects, particularly among late preterm infants subsequently born at term, have renewed interest in optimizing corticosteroid exposure. Experimental data across species, supported by human pharmacokinetic analyses, indicate that fetal lung maturation is driven by sustained low corticosteroid concentrations rather than high peak levels. This commentary summarizes key experimental, pharmacokinetic, and modelling evidence that informed the selection of the lower-dose betamethasone phosphate regimen evaluated in the WHO ACTION-III trial and explains the scientific rationale for this dosing strategy. Pharmacokinetic modeling indicates that 2 mg betamethasone phosphate administered intramuscularly every 12 h for four doses achieves fetal concentrations within the 1 to 4 ng/mL range identified in experimental studies, while avoiding the supratherapeutic peaks observed with conventional regimens. The ACTION-III trial will evaluate whether this lower dose ACS regimen, chosen on the basis of carefully developed models and clinical studies, maintains clinical efficacy while potentially reducing unnecessary systemic corticosteroid exposure in women at risk of late preterm birth.Trial registration: ISRCTN11434567, registered on 7 June 2021.  https://www.isrctn.com/ISRCTN11434567?q=ACTION-III&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10 .</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"27 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148585336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intracluster correlation coefficients for neonatal trials: an analysis of national population level clinical data.","authors":"S Jawad, A T Prevost, C Gale","doi":"10.1186/s13063-026-09893-z","DOIUrl":"10.1186/s13063-026-09893-z","url":null,"abstract":"<p><strong>Background: </strong>Clustering of outcomes occurs naturally in neonatal data due to multiple births clustered by mother and infants clustered within the neonatal unit administering their care. Estimating these cluster effects is important for neonatal study design and impacts upon sample sizes for neonatal trials.</p><p><strong>Methods: </strong>We analysed retrospective data from all neonatal admissions in England and Wales between January 2016 and January 2020 held in the National Neonatal Research Database. Intracluster correlation coefficients (ICCs) and their 95% confidence intervals were calculated for core neonatal outcomes and those commonly used in trials, at the level of both the neonatal unit and mother. Results were stratified by gestational age and neonatal unit level of birth. To illustrate the impact of clustering, the design effect was estimated for a theoretical cluster trial.</p><p><strong>Results: </strong>Intracluster correlation coefficients varied between outcomes and gestational age groups. Neonatal unit level intracluster correlation coefficients were low for mortality (0.0054, 95% CI 0.0039, 0.0068) and other core outcomes (severe necrotising enterocolitis 0.0042, 95% CI 0.0020, 0.0063) and were higher for outcomes related to care delivery (duration of intensive care 0.0237, 95% CI 0.0177, 0.0298; duration receiving parenteral nutrition 0.0265, 95% CI 0.0197, 0.0332). Gestation at birth was inversely correlated with neonatal unit ICC estimates. At the level of the mother, ICC estimates were generally larger, especially for preterm infants.</p><p><strong>Conclusions: </strong>We have estimated ICCs for key neonatal outcomes at the level of both neonatal unit and mother with high precision using national, population-level routinely recorded data. These ICC estimates can be used to inform future neonatal studies and sample size calculations for neonatal trials.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"27 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Considering the timing and appropriateness of trial consent during childbirth: a secondary analysis from the qualitative process evaluation of the ROTATE trial.","authors":"Eleanor Molloy, Jacqueline Nicholls, Dawn Parris, Rachel Plachinkski, Dimitrios Siassakos, Laura Jones","doi":"10.1186/s13063-026-09881-3","DOIUrl":"10.1186/s13063-026-09881-3","url":null,"abstract":"<p><strong>Background: </strong>The ROTATE trial is a multi-centre randomised controlled trial of manual versus instrumental rotation of the fetal head in malposition at birth, to evaluate if manual compared with instrumental rotation reduces the risk of severe maternal perineal trauma, without increasing caesarean birth rates. ROTATE internal pilot phase ran from June 2022 to June 2023 with an embedded qualitative process evaluation (QPE). The QPE aimed to explore the feasibility, acceptability, and appropriateness of the trial for parents and healthcare professionals (HCPs). ROTATE had a two-stage consent process where verbal assent was sought prior to randomisation, and written consent was gained and recorded after the birth. This paper reports a secondary analysis of ROTATE QPE data focusing on gaining informed consent to trial entry in time-pressured maternity settings.</p><p><strong>Methods: </strong>Secondary analysis of data from semi-structured interviews with women (n = 9), their birth partners (n = 3), and HCPs (n = 11). Data were analysed using codebook thematic analysis.</p><p><strong>Results: </strong>Parents and HCP reported that offering a clinical trial at late-stage labour added additional complexities and challenges at a time-pressured period of their labour and birth. Using a layered approach to trial offering, where the trial information was shared prior to full eligibility, and discussed with multiple trusted HCPs, meant clinical trial approaches in late-stage labour can be anticipated. HCPs were concerned whether parents would recall conversations and decision-making about trial entry when they had been under physical and psychological stress in the second stage of labour. The two-stage consent process for ROTATE, using pre-randomisation verbal assent, with post-randomisation and post-birth written consent was considered acceptable to parents and pragmatic for HCPs delivering the trial. Gaining subsequent written consent, combined with appropriate birth partner support at the time of trial approach, was considered supportive of autonomous decision-making for women/birthing parents.</p><p><strong>Conclusions: </strong>Clinical trial approaches in time-pressured maternity settings may be ethically challenging and add additional complexities at an already stressful time. A two-stage consent process, and early, layered information about the potential for participation in intrapartum clinical trials, supported informed consent and autonomous decision-making for women/birthing parents.</p><p><strong>Trial registration: </strong>ISRCTN10193017. Registered on 24 November 2022.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"27 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149196628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut Regulated Associations of Neuronal Signalling in High Blood Pressure (GRAINS-BP): a double-blinded randomised crossover placebo-controlled trial.","authors":"Malindi Welathanthree, Matthew Snelson, Donggyu Rim, Brendan McCarthy, Gianni Sesa-Ashton, David G S Farmer, Chaoran Yang, Jianan Lu, Phoebe T T Cheong, Matthew P Pase, Tracy McCaffrey, Francis J Ha, Sushil Dhital, Esther Davis, Elisabeth Lambert, Vaughan G Macefield, Francine Z Marques, Rikeish R Muralitharan","doi":"10.1186/s13063-026-09911-0","DOIUrl":"10.1186/s13063-026-09911-0","url":null,"abstract":"<p><strong>Background: </strong>Hypertension affects 1 in 3 Australian adults and is a major contributor to stroke and myocardial infarction. Despite the availability of various medications, over 50% of patients struggle to control their blood pressure (BP) due to nonadherence, difficulty finding the right treatment, or avoidance of medication. Diet plays a key role in cardiovascular health, with high-fiber intake shown to lower BP through the production of short-chain fatty acids (SCFAs), metabolites formed during fiber fermentation. A previous clinical trial found that incorporating a specific type of resistant starch - high amylose maize starch enriched with acetate and butyrate (HAMSA/B) - significantly reduced blood pressure in hypertensive patients. While the exact mechanism remains unclear, SCFAs may influence BP via the gut-brain axis by reducing muscle sympathetic nerve activity (MSNA), which has vasoconstrictor function and is elevated in hypertensive individuals.</p><p><strong>Methods: </strong>The GRAINS-BP clinical trial will recruit 29 adults with untreated hypertension (≥ 140/90 mmHg) for a double-blind, cross-over study using HAMSA/B administered as a shake delivered twice daily. The assessment period will span 48 days and include four visits at the Alfred Hospital, Melbourne, Australia. At visit 1, baseline measurement will be taken, including muscle sympathetic nerve activity (MSNA) and electrocardiogram (ECG). Participants will be randomised to the order in which they receive the placebo and HAMSA/B shake. Each intervention period will last 14 days, separated by a 20-day washout before participants cross over to the alternate treatment. At each visit, faecal, urine, and blood samples will be collected to investigate microbiome, cardiometabolic, renal, and immune profiles, respectively. Univariate and multivariate statistical analyses will be conducted to examine treatment effects and to identify correlations among microbiome, cardiometabolic, renal, and immune outcomes.</p><p><strong>Discussion: </strong>This project's primary outcome is change in autonomic nervous system activity. Secondary outcomes include 24-h BP, gut microbiome composition, SCFA levels, immune cell profiles gastrointestinal transit time, quality of life, anxiety and depression symptoms, cognitive function, gut barrier integrity, and circulating micro- and nanoplastics. Findings from this study will reveal whether SCFAs reduce blood pressure by their influence on the autonomic nervous system.</p><p><strong>Trial registration: </strong>This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12625000557437).</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"27 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of time-restricted eating in comparison with energy-restricted diet on expression of BMAL-1 and miRNA-let-7f-1-3p genes, circadian rhythm status, sleep quality, metabolic and anthropometric markers in obese women: a study protocol for a randomized controlled clinical trial.","authors":"Atefeh Tavakoli, Neda Kermani, Parastou Zamani, Bahram Pourghassem Gargari, Parvin Dehghan, Khadijeh Mirzaei","doi":"10.1186/s13063-026-09905-y","DOIUrl":"10.1186/s13063-026-09905-y","url":null,"abstract":"<p><strong>Introduction: </strong>One of the most common chronic diseases is obesity. Disturbances in circadian rhythm and sleep quality are common in these people. Genes related to circadian rhythm control are also disrupted. One of the methods of controlling and reducing obesity is to intervene in the individual's diet, and one of the alternative methods to the conventional low-calorie diet is the use of fasting diets, including time-restricted eating (TRE), which can have effects on the expression of a circadian rhythm genes, the circadian rhythm status, and the quality of sleep. This randomized controlled trial (RCT) will be aimed to examine the effect of the TRE diet in comparison with an energy-restricted diet (ERD) on the expression of basic helix-loop-helix ARNT-Like-1 (BMAL-1) and micro ribonucleic acid (miRNA)-let-7f-1-3p genes, circadian rhythm status, and sleep quality in women with obesity.</p><p><strong>Methods and analysis: </strong>This study will be conducted on 42 obese women. Participants will be randomly assigned to receive either 16:8 TRE (fasting from 8 to 12 PM the next day) or an ERD (55% carbohydrate, 30% fat, 15% protein) diet for 12 weeks. Gene expression, circadian rhythm status, sleep quality, anthropometric measurements, and metabolic evaluations will be assessed before and after the intervention. Dietary evaluations will be performed at baseline, middle, and end of the study.</p><p><strong>Discussion: </strong>Since circadian rhythm-related gene expression has a role in circadian rhythm and ultimately obesity regulation, it seems that TRE, as a dietary approach, can affect these gene expressions.</p><p><strong>Trial registration: </strong>Iranian Registry of Clinical Trials (IRCT20100123003140N25), which was registered and approved on 28 July 2025 ( https://irct.behdasht.gov.ir/user/trial/84484/view ).</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148498091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}