Trials最新文献

{"title":"Effects of a calorie-restricted MIND diet and probiotic supplementation on fertility, sexual function, and quality of sexual life in overweight and obese men: protocol for a double-blind randomized clinical trial.","authors":"Ali Shamsi-Goushki, Mohammad Reza Mahmoodi, Sareh Ashourzadeh, Majid Khadem-Rezaiyan, Reza Rezvani","doi":"10.1186/s13063-026-09891-1","DOIUrl":"10.1186/s13063-026-09891-1","url":null,"abstract":"<p><strong>Background: </strong>MIND diets and probiotics have the potential to positively affect infertility in obese and overweight men, but their effects are not yet fully elucidated. Therefore, this study aims, for the first time, to address this gap by evaluating the effects of a calorie-restricted MIND diet and probiotic supplementation on fertility, sexual function, and quality of sexual life in overweight and obese men.</p><p><strong>Methods: </strong>This study will be conducted as a double-blind randomized clinical trial on 84 overweight and obese men in Kerman for 3 months. Participants will be randomly allocated to one of the following four groups: (1) the group receiving the MIND diet with restricted calories + probiotic supplement; (2) the group receiving the MIND diet with restricted calories + placebo; (3) the group receiving a standard low-calorie diet + probiotic supplement; (4) the group receiving a standard low-calorie diet + placebo. Before the intervention and after 3 months, the study variables will be compared between groups. Anthropometric evaluation, spermogram evaluation, serum levels of androgens, sexual function, and quality of sexual life will be assessed at the beginning and at the end of the study.</p><p><strong>Discussion: </strong>This trial will provide valuable evidence regarding the potential synergistic effects of the MIND diet and probiotic supplementation in managing male infertility associated with obesity. By evaluating both clinical fertility markers and patient-reported outcomes such as sexual function and quality of life, the study findings are expected to contribute to a better understanding of the role of lifestyle interventions in reproductive health, potentially offering a sustainable therapeutic approach for this population.</p><p><strong>Ethical aspects: </strong>All the work procedures will be carried out in accordance with the guidelines recommended by the Ethics Committee of Mashhad University of Medical Sciences (IR.MUMS.REC.1402.341).</p><p><strong>Trial registration: </strong>Iranian Registry of Clinical Trials IRCT20240313061277N1. Registered on 31 March 2024.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148438121","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":"Designing clinical research on hyperbaric oxygen therapy: a narrative review and practical methodological guide.","authors":"Halimureti Simayijiang, Yueling Lin, Tingting Zhong, Zhuo Li, Kun Zhang, Ying Long","doi":"10.1186/s13063-026-09895-x","DOIUrl":"10.1186/s13063-026-09895-x","url":null,"abstract":"<p><p>This article provides an overview of the main study designs for hyperbaric oxygen therapy (HBOT) clinical research. Based on study objectives, study types and use cases across different phases and settings are described, including before-and-after studies to detect early signals and feasibility, randomized controlled trials, including pragmatic RCTs, to confirm causality, multicenter stratified or adaptive designs to optimize protocols, and real-world studies to evaluate real-world effectiveness, safety, adherence, and health economic outcomes. To improve comparability and reproducibility, the following key elements are also proposed: the use of a pre-specified, pooled set of intervention parameters in each study (pressure, session duration, frequency, and overall course), the establishment of consistent and feasible inclusion and exclusion criteria, and the creation of a multilevel outcomes framework focusing on objective clinical endpoints and patient-reported outcomes, including specific safety and adherence monitoring. To overcome common challenges in HBOT research-protocol heterogeneity, blinding difficulties, interindividual variability in responses, and limitations in evidence synthesis-the article recommends standardized multicenter templates, stratified randomization, a predesigned statistical analysis plan, and mechanisms for data registration and sharing to enable cross-study pooling and long-term follow-up. Finally, a stepwise research pathway is proposed that begins with signal detection and confirmatory studies, progresses through parameter optimization and practice expansion, and ultimately leads to the creation of standardized clinical pathways and generalizable results. The goal is to provide a concise, practical methodological reference for proposal writing, funding applications, and implementation planning, thereby supporting more rigorous HBOT research in neurorehabilitation, tissue repair, chronic disease management, and healthy aging, particularly where current evidence remains exploratory or heterogeneous. This article is not intended as a systematic review of HBOT efficacy; instead, it is positioned as a narrative methodological review that uses current evidence limitations to inform trial design, feasibility assessment, interpretation, and transparent reporting.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148438129","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":"Pinpointing precision: axial length and refraction in paediatric myopia trials-a mixed methods study.","authors":"Annegret H Dahlmann-Noor, Nick Freemantle","doi":"10.1186/s13063-026-09884-0","DOIUrl":"10.1186/s13063-026-09884-0","url":null,"abstract":"<p><strong>Purpose: </strong>Most paediatric myopia intervention trials report two primary outcomes: axial length and cycloplegic autorefraction. Having one single primary outcome would increase trial efficiency, reduce participant burden, and may improve trial retention. This article aims to evaluate precision of axial length and cycloplegic autorefraction and to explore eye care professionals' and young people's views of cycloplegia.</p><p><strong>Methods: </strong>Mixed methods study with meta-analysis of axial length and cycloplegic spherical equivalent measurements reported by paediatric myopia treatment trials; interviews with eye care professionals; engagement/involvement discussion with children and young people.</p><p><strong>Results: </strong>In the meta-analysis, mean effect size (standard error, SE) was -0.52 (0.12, p < 0.001, 95% confidence interval (CI) -0.76 to -0.29) for axial length and 0.49 (0.11, p < 0.001, CI 0.27 to 0.71) for cycloplegic spherical equivalent refraction. Difference in mean point estimates was 0.033, SE of the difference 0.164 (CI -0.29 to +0.535). With t-statistic (mean difference/SE of mean difference) of 0.20, two-tailed p value was 0.84. Eye care professionals report that children dislike cycloplegia, describing discomfort, distress, and potential refusal to attend follow-up appointments. Children and young people describe pain and discomfort, remember prolonged effects such as blurred vision and light sensitivity, and complain about receiving insufficient information about adverse effects.</p><p><strong>Conclusions: </strong>Whilst the precision of axial length and cycloplegic autorefraction spherical equivalent measurements is similar, cycloplegic autorefraction requires longer study visits and inflicts more discomfort. In the design of future trials, researchers, funders, and regulators should consider increasing trial efficiency by selecting axial length as primary outcome and removing cycloplegic refraction from follow-up assessments.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13640285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424516","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":"Air purifiers in classrooms for infection control: a pilot study including a randomized multiple crossover trial to evaluate effectiveness in reducing particulate matter.","authors":"Cathinka Halle Julin, Ingeborg Hess Elgersma, Runar Barstad Solberg, Christine Holst, Arnfinn Helleve, Christopher James Rose, Unni Gopinathan, Atle Fretheim, Petter Elstrøm, Sverre B Holøs","doi":"10.1186/s13063-026-09839-5","DOIUrl":"10.1186/s13063-026-09839-5","url":null,"abstract":"<p><strong>Background: </strong>Air purifiers with high-efficiency particulate air (HEPA) filters aim to reduce particulate matter from the air, including infectious aerosols, potentially lowering airborne disease transmission in classrooms. This pilot study, informing a larger randomized trial (RCT), explored the acceptability and feasibility of air purifiers in classrooms, and estimated their effect on particulate matter (PM_2.5) concentration.</p><p><strong>Methods: </strong>This study, conducted in schools in the greater Oslo area, Norway, from January to April 2023, consisted of two parts lasting 6 and 9 weeks, respectively. In part 1, eligible primary school classrooms received either ceiling-mounted or portable purifiers. In part 2, we conducted a three-arm randomized multiple crossover trial of ceiling-mounted versus portable purifiers versus no air purification. Schools with three classrooms on the same floor with adequate space for air purifiers were eligible. We evaluated acceptability and feasibility of installing and operating air purifiers by collecting interview data from students (part 1) and teachers (parts 1 and 2). The feasibility of collecting consent and questionnaires from students' legal guardians and student absences from municipality records was explored. We evaluated superiority of air purification versus no air purification and noninferiority of portable versus ceiling-mounted air purifiers on PM_2.5 concentration using sensor measured air quality data.</p><p><strong>Results: </strong>Five primary schools (five classrooms) and one adult education school (three classrooms) participated in parts 1 and 2 of the study, respectively. Ceiling-mounted and portable air purifiers were feasible to install and operate and were well-accepted by students (n = 11) and teachers (n = 7). No harms were reported. Consent and questionnaires were collected from 23 of 114 students' legal guardians. Collecting absence data from municipality records was feasible, although inconsistencies in teachers' recording affected weekly accuracy. Air purification was superior to no air purification in reducing PM_2.5 concentration (p = 0.011), and portable purifiers were noninferior to ceiling-mounted units (p < 0.001) and significantly reduced PM_2.5 compared to no air purification (rate ratio 0.71; 95% CI 0.57-0.89).</p><p><strong>Conclusions: </strong>Installing and operating air purifiers in classrooms is feasible and acceptable. Portable purifiers are user-friendly and reduce PM_2.5 concentration. It was challenging to obtain consent from students' legal guardians to collect absence data; municipality records proved more practical. A larger RCT on air purifier effectiveness in schools will be feasible if data collection challenges can be overcome.</p><p><strong>Trial registration: </strong>NCT06374316 (retrospectively registered 15 April 2024).</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13640335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424544","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":"Vulnerability, protection and fairness: ethical and regulatory limits in small-N gene therapy trials.","authors":"Margaux Reckelbus, Eva Van Steijvoort, Isabelle Huys, Pascal Borry","doi":"10.1186/s13063-026-09896-w","DOIUrl":"10.1186/s13063-026-09896-w","url":null,"abstract":"<p><strong>Background: </strong>International ethics frameworks emphasize both the protection of vulnerable participants and the importance of equitable inclusion in research. In ultra-rare gene therapy trials, extensive safety monitoring, long-term follow-up requirements, and specialized treatment infrastructure are necessary to ensure participant protection and scientific validity. However, these requirements operate within healthcare systems characterized by geographic, financial, and social inequalities, raising concerns about whether all eligible patients have a fair opportunity to participate. Recent regulatory reforms in the European Union (EU), United Kingdom (UK), and United States (US) increasingly promote methodological flexibility for small patient populations through adaptive trial designs, risk proportionate oversight, and alternative evidentiary approaches.</p><p><strong>Main body: </strong>This commentary examines the extent to which existing clinical trial guidance for gene therapy promotes fair inclusion while safeguarding participants. We analyze binding and non-binding guidance from the European Medicines Agency (EMA), United States Food and Drug Administration (FDA), Medicines and Healthcare products Regulatory Agency (MHRA), International Council for Harmonisation (ICH), Council for International Organizations of Medical Sciences (CIOMS), and United Nations Educational, Scientific and Cultural Organization (UNESCO), alongside illustrative examples from Zolgensma®, Roctavian®, and Hemgenix®. Current frameworks provide substantial methodological flexibility with natural history data, external controls, decentralized approaches, and proportionate evidence requirements. Emerging initiatives such as FDA Diversity Action Plans, the UK Inclusion and Diversity Plan, and recent EU regulatory reforms further reflect growing attention to procedural fairness. Nevertheless, operational barriers remain. Long-term follow-up obligations, geographic concentration of expertise, financial burdens, and reliance on patient advocacy networks continue to shape who can realistically participate in research. While regulators increasingly recognize these challenges, guidance rarely requires concrete measures to mitigate them.</p><p><strong>Conclusion: </strong>Current gene therapy trial frameworks largely succeed in supporting methodological flexibility for ultra-rare conditions but insufficiently operationalize fair inclusion. Ethical concerns arise not because participant protections are excessive, but because the burdens associated with necessary scientific and regulatory requirements may disproportionately affect patients facing structural disadvantages. Ensuring justice in ultra-rare gene therapy research requires extending proportionate, risk-based approaches beyond evidence generation to include the identification and mitigation of foreseeable barriers to participation.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"27 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13355327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424510","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":"Efficacy of blended digital and face-to-face psychotherapy compared to enhanced psychotherapy for patients with Somatic Symptom Disorder (iSOMA+): study protocol for a multicenter randomized controlled pragmatic trial.","authors":"Freda Kristine Jutzi, Michael Witthöft, Harald Baumeister, Mira Denninger, Winfried Rief, Gaby Bleichhardt, Josef Bailer, Peter Kirsch, Maja Halli-Erkic, Daniela Mier, Mara Mankin, Julia A Glombiewski, Rabea Vogt, Jens Heider, Frank Jacobi, Alexandra Martin, Barbara Schulte-Holthausen, Kai Kronfeld, Stanislav Gorbulev, Christian Ruckes, Rüdiger Pryss, Robin Kraft, Severin Hennemann","doi":"10.1186/s13063-026-09886-y","DOIUrl":"10.1186/s13063-026-09886-y","url":null,"abstract":"<p><strong>Background: </strong>Persistent somatic symptoms (PSS) that occur in various somatic, functional, or mental health conditions can lead to considerable psychological distress and functional impairment. As such, they are a key characteristic of the Somatic Symptom Disorder (SSD) in DSM-5. While psychological treatments such as cognitive behavioral approaches can address these symptoms, their clinical efficacy in reducing symptom burden in previous trials remains limited. Blended psychotherapy, i.e., combining face-to-face psychotherapy with digital elements, is a promising new approach to efficiently enhance psychotherapeutic effects. This study therefore aims to evaluate the efficacy, mechanisms, and safety of blended psychotherapy compared to enhanced standard psychotherapy for individuals with SSD in outpatient psychotherapy.</p><p><strong>Methods: </strong>A two-armed, multicenter randomized controlled pragmatic trial will be conducted, and N = 250 adults with SSD will be randomized to either blended psychotherapy (20 individual sessions of cognitive behavioral therapy (CBT) + accompanying digital intervention; iSOMA+) or enhanced CBT (20 sessions of CBT + self-help booklet; CBT+). Participants are recruited at eight German university outpatient psychotherapy clinics. Assessments will be conducted at patient study inclusion (pre-treatment), during treatment, post-treatment, and 6 months follow-up. The primary outcome is the reduction in somatic symptom severity using the Screening for Somatoform Disorders (SOMS-7R) from baseline to post-treatment. Secondary outcomes include changes in symptom-related distress, coping, self-efficacy, as well as depression, anxiety, health anxiety, disability, quality of life, interpersonal relationship experiences and patient safety. Additionally, several potential moderators and mediators, including patient and intervention characteristics, will be examined.</p><p><strong>Discussion: </strong>This trial investigates the potential of blended CBT for improving treatment outcomes in patients with SSD and will provide evidence on the effects of active vs. passive self-help as treatment augmentation under pragmatic care conditions. By identifying prescriptive factors of treatment response, the study will support personalized care and contribute to more accessible and efficacious treatment options for patients with PSS.</p><p><strong>Trial registration: </strong>German Clinical Trials Register (DRKS) DRKS00035250. Registered on 13.06.2025, https://drks.de/search/de/trial/DRKS00035250 .</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":"27 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424552","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":"Secondary Prophylaxis of Recurrent Clostridioides difficile Infections During Systemic Antibiotics with Vancomycin (SPORES-V): study protocol for a randomized controlled trial.","authors":"Connor Prosty, Alex Carignan, Adrienne K Chan, Yan Chen, Peter Daley, Nick Daneman, Christopher Kandel, Yves Longtin, Santiago Perez-Patrigeon, Terry Wuerz, James Cheaveau, Susy S Hota, Olusola Ogundipe, Theodore S Steiner, Jennifer L Y Tsang, Patrick Archambault, Marco Bergevin, James M Brophy, Gabriel Girouard, Ling Kong, Leighanne Parkes, Sharon Reinblatt, Derek MacFadden, Todd C Lee, Emily G McDonald","doi":"10.1186/s13063-026-09883-1","DOIUrl":"10.1186/s13063-026-09883-1","url":null,"abstract":"<p><strong>Background: </strong>Clostridioides difficile infection (CDI) is a prevalent, morbid, and expensive disease that recurs in approximately 25% of patients despite treatment. Re-exposure to systemic antibiotics is one of the strongest risk factors for recurrence. Observational evidence and two small randomized controlled trials suggest that secondary vancomycin prophylaxis during antibiotic re-exposure may prevent recurrences, but the current evidence is not definitive.</p><p><strong>Methods: </strong>SPORES-V is a Bayesian multicenter phase III double-blind randomized controlled trial. Patients with CDI in the preceding 120 days who are re-exposed to systemic antibiotics will be randomized to receive prophylactic oral vancomycin (125 mg orally twice daily while on antibiotics and then once daily for 7 days afterwards) or an equal schedule of placebo. The primary outcome is CDI recurrence at day 56, analyzed by intention to treat using an adjusted odds ratio. Secondary outcomes include adverse events, discontinuation due to toxicity, longer-term recurrences (120 days), healthcare usage (56 and 120 days), and all-cause mortality (56 and 120 days). SPORES-V has begun recruitment at the McGill University Health Centre site.</p><p><strong>Discussion: </strong>The SPORES-V trial will provide high-quality evidence on the efficacy and safety of secondary vancomycin prophylaxis in the prevention of recurrent CDI.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT06979609. Registered on May 13, 2025, https://clinicaltrials.gov/study/NCT06979609 .</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148413013","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":"Auditory neuromodulation-based prescription digital therapeutic for insomnia disorder: study protocol for a randomized controlled trial (SERENE).","authors":"Kyunghee Kim, Hyeonjoong Kim, Hyeyun Kim, Jung-Won Shin, Jun-Sang Sunwoo, Jung-Ick Byun, Kyoung Jin Hwang, Jiyeon Ha, Mangyeong Lee, Juhee Cho, Jonghwa Jeonglok Park, Ki-Young Jung","doi":"10.1186/s13063-026-09880-4","DOIUrl":"10.1186/s13063-026-09880-4","url":null,"abstract":"<p><strong>Background: </strong>Insomnia affects 10-15% of adults worldwide, significantly impairing quality of life, cognitive function, and work productivity. Current treatments present fundamental trade-offs: cognitive behavioral therapy for insomnia (CBT-I) demonstrates sustained efficacy but requires a prolonged treatment period, specialized therapists, and high patient engagement, while pharmacotherapy provides rapid relief but carries risks of dependence and cognitive impairment that limit long-term use. Existing prescription digital therapeutics (PDTs) address CBT-I's accessibility barriers but inherit its delayed therapeutic onset and adherence challenges. BELL-001 is an auditory neuromodulation-based PDT designed to induce autonomic downregulation through real-time biosignal-responsive acoustic feedback, targeting hyperarousal as a core pathophysiological feature of insomnia.</p><p><strong>Methods: </strong>This is a multicenter, prospective, randomized, double-blind, sham-controlled, superiority trial designed to evaluate the efficacy and safety of BELL-001 in adults with insomnia. A minimum of 114 participants aged 19-75 years diagnosed with insomnia according to ICD-10 criteria (F51.0 or G47.0) and with an Insomnia Severity Index (ISI) score ≥ 15 will be enrolled from six clinical sites in the Republic of Korea. Eligible participants will be randomly assigned in a 1:1 ratio to either the treatment group using BELL-001 or the control group using a sham device. The primary endpoint is the change in ISI score from baseline to 4 weeks. Secondary endpoints include the response rate (ISI reduction ≥ 6 points), subjective sleep onset latency and wake after sleep onset from sleep diaries, and validated questionnaires assessing sleepiness, fatigue, depression, anxiety, quality of life, and work productivity. Treatment-emergent adverse events will be evaluated for safety analysis.</p><p><strong>Discussion: </strong>The SERENE trial will evaluate whether an auditory neuromodulation-based PDT can provide clinically meaningful improvements. If efficacy and safety are demonstrated, this study may support the potential of neuromodulation-based digital therapeutics as an additional treatment option for patients with insomnia disorder. TRIAL REGISTRATION {4}: ClinicalTrials.gov (NCT07295431). Registered on 22 December 2025. https://clinicaltrials.gov/study/NCT07295431.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424500","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":"Correction: High-protein enteral nutrition in intensive care unit patients undergoing advanced early mobilization: protocol for a randomized controlled trial.","authors":"Ginga Suzuki, Yuji Iwanami, Masayoshi Nakazawa, Shunta Yoshioka, Masashi Furuta, Masaru Nakanishi, Hiromi Kanayama, Kohei Ishikawa, Saria Nishioka, Toshimitsu Kobori, Yuka Masuyama, Saki Yamamoto, Yui Shimanuki, Hibiki Serizawa, Yoshimi Nakamichi, Mitsuru Honda, Naohiro Washizawa, Ikuko Okuni","doi":"10.1186/s13063-026-09898-8","DOIUrl":"10.1186/s13063-026-09898-8","url":null,"abstract":"","PeriodicalId":23333,"journal":{"name":"Trials","volume":"27 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424507","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":"Understanding the small print: a 5-year review of readability in phase I trial information leaflets.","authors":"Kate Dodd, Tim Rowland, Hassan Burhan, Amin Sammour, Richard J FitzGerald, Lauren E Walker","doi":"10.1186/s13063-026-09889-9","DOIUrl":"10.1186/s13063-026-09889-9","url":null,"abstract":"<p><strong>Background: </strong>Understanding trial information is essential for participants to give truly informed consent. Current guidance suggests that health information should be accessible to readers with a reading age of 11 years. Readability describes how easily text can be understood, while reading age represents the minimum age at which a typical reader is likely to be able to understand the material. This study examines the readability and reading age of participant information leaflets (PILs) used in recent phase I clinical trials to assess how well they align with recommended standards.</p><p><strong>Methods: </strong>This single-centre study analysed phase I participant information leaflets (PILs) produced between 2017 and 2022. Five established readability tools were used to assess readability and reading age: Flesch Reading Ease, Flesch-Kincaid Grade Level, Gunning Fog Index, Fry Readability and Simple Measure of Gobbledygook (SMOG) Index. Readability was compared between academic and industry-developed PILs.</p><p><strong>Results: </strong>A total of 46 PILs were analysed in this study: 38 (82.6%) industry and 8 (17.4%) academic-led clinical trials. PILs had a mean (± SD) total word count of 8426 (± 2002). The overall mean readability scores, and equivalent reading ages were as follows: Flesch Reading Ease: 53.5 - age 15 + ; Flesch-Kincaid Grade Level: 9.9 - age 14-15; Gunning Fog Index: 11.6 - age 16-17; Fry Readability: 9.9 - age 14-15; SMOG: 13.5 - age 19 + . Academic PILs were more readable than industry PILs, with statistically significant differences for the Flesch Reading Ease (p = 0.046), Gunning Fog Index (p = 0.035), Fry Readability (p = 0.041), and SMOG Index (p = 0.010). No significant difference was observed for the Flesch-Kincaid Grade Level.</p><p><strong>Conclusions: </strong>All PILs were written at a reading age far above recommended levels, raising concerns that many potential participants, particularly those with lower literacy or living in areas of higher deprivation, may struggle to understand essential trial information or may be deterred from taking part altogether. While readability formulas capture only one dimension of comprehensibility, these findings highlight an urgent need to redesign PILs to reduce reading age and to evaluate how improving readability impacts participant understanding and informed consent.</p>","PeriodicalId":23333,"journal":{"name":"Trials","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424587","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}