Trials最新文献

Background: Traumatic tympanic membrane perforation (TTMP) is common worldwide, with a reported incidence as high as 6.1%. Conventional management advocates keeping the ear canal dry and strictly avoiding topical ear drops. Under this "dry-ear" regimen, however, tympanic membrane (TM) healing is often slow and often ineffective, especially for large perforations. We previously demonstrated that both exogenous growth factors and 0.3% (w/v) ofloxacin eardrops can accelerate closure of TTMP, with no significant difference in efficacy between the two treatments. This raised the question of whether the moist environment itself-rather than the mitogenic effect of the growth factor-might be the principal driver of repair. To test this hypothesis, we sought to evaluate the effect of moisture by creating a purely humid milieu. Normal saline is the standard vehicle used to maintain a moist wound bed in cutaneous healing, yet to date no clinical study has evaluated its efficacy in TTMP repair.

Objective: This study intends to verify whether the moist environment alone can result in a better TTMP healing than a dry environment and to confirm the additional effect of ofloxacin and growth factor.

Methods: The study will compare the TTMP healing across dry versus moist environments created by saline, 0.3% (w/v) ofloxacin, or basic fibroblast growth factor (bFGF). The first phase will enroll 130 patients randomized evenly into the moisture group and the control group, with 65 each. If the moisture group demonstrates significantly shorter healing times and a superior sealing rate, the second phase will be launched as a triple-blind randomized controlled trial (RCT) with 150 patients who will be assigned into one of the three groups ((i) saline, (ii) ofloxacin, and (iii) bFGF). Otoscopy will be performed pre-treatment and weekly post-treatment to assess perforation size and signs of middle-ear infection (e.g., secondary purulent otorrhea) until closure or up to 3 months, whichever comes first. A comprehensive hearing test, including pure-tone audiometry, tympanometry, and distortion product otoacoustic emissions (DPOAE), will be conducted before and after perforation closure.

Ethics and dissemination: This study has been approved by the Medical Ethics Committee of Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital (approval number 2023-006-(1)). The results from this study will be published in peer-reviewed journals and presented at relevant conferences.

Trial registration: ChiCTR ChiCTR2400084582, Registered on 21 May 2024. https://www.chictr.org.cn/bin/project/edit?pid=224331 .

Background: Post-traumatic stress disorder (PTSD) presents significant mental health challenges for veterans, leading to substantial physical, cognitive, and psychological difficulties, including heightened risks of social issues and suicidal ideation. Adaptive Disclosure (AD) is a novel, emotion-focused Cognitive Behavioral Therapy (CBT) approach developed by the military for combat-related PTSD. This technique involves exposure therapy and an empty-chair technique, allowing patients to verbalize unresolved issues. Despite its short, six-session duration, AD appears well-tolerated and effective in reducing PTSD symptoms. Given the limited global studies and their absence in Iran, this study will be conducted to investigate AD's impact on reducing PTSD symptom severity in veterans.

Methods: This randomized clinical trial will explore AD's effect on PTSD symptom severity. A total of 58 participants (29 per group) will be recruited via available sampling from Shahid Rajaee and Salman Hospitals in Yasuj. Participants must be veterans aged 18 or older, with diagnosed PTSD, sufficient insight for AD (assessed via Mental Status Exam), and informed consent. Exclusions include severe mental disorders (e.g., psychotic or bipolar type I), recent suicidal/homicidal ideation (within 3 months), or concurrent systematic trauma-focused therapies. The intervention group will receive six weekly 90-min AD sessions. The control group will receive no intervention during this period. Immediately after the intervention, both groups will complete the research questionnaire. Following the study, the control group will also be offered education on the Adaptive Disclosure technique. The primary outcome, severity of post-traumatic stress disorder symptoms, will be measured using the Post-Traumatic Stress Disorder Checklist- Civilian Version (PCL-C), a 17-item self-report scale. Data will be analyzed with SPSS version 27. Ethical approval has been secured from Yasuj University of Medical Sciences (Supplementary File 2).

Discussion: The results are expected to offer vital insights into AD's effectiveness for veterans with PTSD. If successful, this approach could inform policymakers for healthcare guidelines and aid psychiatric nurses in symptom alleviation. This research will significantly contribute to the scientific community by providing the first empirical evidence of AD's efficacy in an Iranian veteran population, expanding knowledge on culturally relevant treatments for combat-related PTSD, and potentially informing clinical practices nationally and internationally.

Trial registration: IRCT number IRCT20160815029377N4. Registered on 03/05/2025.

Background: Depression affects almost 60% of stroke survivors, impacting on recovery and quality-of-life. Depression may be treated with medication or talk-based therapies. One randomised controlled trial showed a talk-based therapy called motivational interviewing-based intervention (MIBI) delivered early after stroke reduced depressive symptoms at 3 and 12 months post-stroke compared with receiving usual care alone. However, it was unclear if the benefit was due to the specific MIBI components or simply the additional attention received. This trial aims to determine the effect of MIBI plus usual care on reducing depressive symptoms post-stroke, relative to usual care (UC), and to an attention control (AC) (social attention without therapeutic content, i.e. general conversation).

Methods: Patients admitted following acute stroke meeting the study eligibility criteria (not currently receiving talk-based therapy and not currently having severe depression) will be recruited across 18 UK hospitals within 28 days of stroke. A total of 1287 participants will be randomised on a 1:1:1 ratio into three groups: MIBI + UC; AC + UC; UC. Participants in MIBI + UC and AC + UC will additionally have remote (telephone/online) sessions with MIBI therapists or AC providers respectively, for four 45-min weekly sessions, beginning within 6 weeks of randomisation. Participant self-report measures of depression (primary outcome, Patient Health Questionnaire (PHQ-9) at 3 months) and quality-of-life will be collected at baseline, 6 weeks and 3 months post-randomisation. The proposed mechanism of effect, via participants' self-efficacy and confidence, and the impact of MIBI dose and/or therapeutic alliance on outcome will also be explored. If benefit of MIBI + UC over UC is demonstrated, mixed effects regression will be fitted to outcome data from all three arms, and appropriate parametrisation with MIBI + UC as the reference group. A mixed-methods process evaluation comprising quantitative assessment of intervention adherence and fidelity and semi-structured interviews with a purposive sample of study participants (n ~ 18) and MIBI/AC staff (n ~ 15) will explore participation, acceptability, and considerations for implementation. An economic evaluation will explore cost-effectiveness.

Discussion: The results will inform whether any observed improvements in mood are a natural change over time, due to attention, or a therapeutic change attributable to MIBI. If MIBI is shown to effectively reduce depressive symptoms, the process evaluation will inform implementation of the intervention into clinical care.

Trial registration: ISRCTN, ISRCTN17065351. Registered 01/02/2022, https://www.isrctn.com/ISRCTN17065351 .

Background: In Malaysia, adolescent anxiety and depression are increasing faster than ever, and rates of suicidal behaviour are rising especially among those living in deprived communities. However, Malaysia's mental health system is currently constrained by limited workforce capacity, affecting the delivery of effective interventions. The overall aim of this trial is to use a school-based intervention to promote mental health among at-risk adolescents from low-income communities in Malaysia. Our primary aim is to evaluate the effectiveness and cost-effectiveness of a school-based intervention ("Super Skills for Life"; SSL) in reducing anxiety and depression, and in improving mental wellbeing in adolescents aged 12-14 years. We also aim to determine the characteristics of adolescents who benefit from SSL, compared to those who do not, as well as to identify contextual factors related to the successful implementation of SSL in Malaysian schools.

Methods: The design will be a two-arm, cluster randomised controlled trial comparing school-based intervention (Super Skills for Life; SSL) to study skills control condition (Study Skills Programme; SSP) using a 1:1 allocation ratio. Classrooms will be the cluster unit for randomisation. Three stratification factors will be used for randomisation: school size, classes/forms and school location (urban vs rural). The study will recruit adolescents in at least 20 secondary schools in economically deprived, rural and urban regions in Malaysia. These adolescents will be invited to complete a screening questionnaire (i.e. Depression Anxiety and Stress Scale-21; DASS-21). Based on power calculation, 428 adolescents (214 per arm) who experience moderate to severe levels of anxiety and depression on the DASS-21 will be invited to participate in the trial. Classes will be randomly allocated to SSL or SSP, with eligible adolescents from each class receiving the allocated intervention. Assessment will be conducted at screening, at pre- (i.e. baseline) and post-intervention (i.e. 2 months), and at two follow-ups (i.e. 6 and 12 months post-intervention). The primary outcomes will be a reduction in anxiety and depressive symptoms, and an improvement in mental wellbeing at 12 months post-intervention.

Discussion: Findings of this trial will determine if delivering a group school-based intervention by school staff for adolescents at risk of anxiety and depression is effective and cost-effective. The findings will advance understanding of the role of school staff in the delivery of a school-based intervention and will generate new knowledge on the role of socio-cultural and other contextual factors in predicting intervention uptake and treatment outcome.

Trial registration: ClinicalTrials.gov NCT07138664. Registered on August 16, 2025.

Background: As with most Sub-Saharan African countries, Nigeria has a rising incidence of cancer, with disproportionate mortality rates. The financial burden of cancer care often results in catastrophic healthcare spending, leading to treatment refusal, disruption, and discontinuation. This is particularly significant in Nigeria, where nearly all patients are uninsured, and out-of-pocket costs often exceed households' ability to pay. Financial navigation programs (FNPs) have been shown to mitigate treatment-related financial toxicity in cancer care and reduce treatment abandonment, but there is a paucity of high-quality data on this intervention in resource-constrained settings. Here, we present a randomized controlled trial to evaluate the impact of a novel FNP in Nigeria.

Methods: We designed the COST-FIN trial, a multi-site pragmatic single-blinded randomized controlled trial of newly diagnosed (<6 weeks from diagnosis) adults (≥18 years) with breast, colorectal, or prostate cancer at two tertiary cancer centers in Nigeria. Participants (n = 200) will be randomized (1:1) to either the intervention (FNP) or the control arm and followed for 12 months. Data on key individual, treatment, and financial parameters will be collected via structured interviews and chart abstraction at baseline, 3-, 6-, and 12-month follow-up. In addition, participants randomized to the FNP will receive a tailored financial literacy assessment, financial planning support, and enhanced access to resources by trained financial navigators. Primary and secondary outcomes are financial catastrophe (FC) and financial distress (FD), respectively. Exploratory outcomes will include cost-related non-adherence and cost-effectiveness of the program. An interim analysis will be conducted when 50% of the estimated accruals reach 6 months of follow-up, with crossover if compelling evidence of benefit is demonstrated at that time point. All participants will be followed for 12 months from recruitment.

Discussion: This first-of-its-kind study will provide evidence on the role of FNP in potentially eliminating financial barriers to cancer care in Nigeria. Given the country's renewed interest in cancer control through the passage of the National Cancer Control Plan, findings from this study have the potential to influence policy reform and set the stage for further studies to evaluate the scalability and implementation of similar interventions in resource-limited settings.

Trial registration: ClinicalTrials.gov NCT06630962 . Registered on Oct 8, 2024.

Background: Benign paroxysmal positional vertigo (BPPV), particularly involving the posterior semicircular canal (PC-BPPV), is the most common peripheral vestibular disorder, characterized by brief episodes of vertigo triggered by positional changes. It affects quality of life, increases fall risk, and restricts daily and occupational activities. Vestibular rehabilitation therapy (VRT) is an exercise-based approach that is commonly used in clinical management. Mobile health-based formats represent a delivery option for vestibular rehabilitation in the management of PC-BPPV, through structured, user-accessible applications such as the Vertigo Coach. The application integrates habituation, gaze stabilization, and balance exercises with progress tracking and educational content and functions as a structured adjunct to canalith repositioning techniques for presenting exercises and documenting usage. Although preliminary studies indicate feasibility, high-quality evidence from randomized controlled trials evaluating smartphone-based vestibular rehabilitation remains limited.

Objective: To evaluate the effects of smartphone-based habituation exercises compared with conventional booklet-based exercises, when combined with CRTs, on dizziness, vertigo severity, and quality of life in individuals with PC-BPPV.

Methods: A single-blind, two-arm parallel-group randomized controlled trial will be conducted with 84 participants aged 18-65 years diagnosed with PC-BPPV. Participants will be randomized into two groups: Group A (n = 43) will receive a printed instructional booklet, and Group B (n = 43) will use the Vertigo Coach smartphone application. Both groups will receive standardized CRTs. A 6-week VRT program will be delivered in the assigned format, with assessments at baseline, 3 weeks, and 6 weeks. Primary outcomes include dizziness severity, vertigo-related disability, and quality of life, measured using validated tools.

Discussion: Mobile health-based formats may provide an alternative method for delivering vestibular rehabilitation in the management of PC-BPPV. This trial will examine whether app-based VRT produces comparable or differential effects relative to booklet-based home programs when administered with CRTs. The findings may inform the use of digital formats for vestibular rehabilitation by providing data on feasibility, symptom change, and user-reported outcomes. Such approaches may offer structured home-based exercise information and facilitate access to rehabilitation resources.

Ethics and dissemination: The trial has been reviewed and approved by the Institutional Ethics Committee (reference no. DMIHER (DU)/IEC/2025/628).

Trial registration number: CTRI/2025/03/083581. Registered on April 2nd 2025.

Background: Heart failure (HF) is a chronic condition characterized by significant functional limitations, with exercise intolerance as a major determinant of reduced quality of life. Supervised aerobic exercise is a core intervention in cardiac rehabilitation, yet adherence and tolerance may be hindered by physical and motivational factors. Immersive technologies such as virtual reality (VR) have shown potential to increase engagement and positive perceptions during exercise. This study aims to evaluate the influence of VR on tolerance to cycle-ergometer aerobic exercise in hospitalized patients with HF.

Methods: We will conduct a randomized, controlled, parallel-group trial with 1:1 allocation. Adult inpatients with a diagnosis of HF will be screened for eligibility and randomly assigned to two groups: control (cycle-ergometer aerobic exercise) and intervention (the same exercise combined with an Meta Quest 2 VR device). Each participant will complete a single session of up to 20 min, consisting of five blocks of 3 min of continuous pedaling interspersed with one-minute passive rests, with early termination in case of intolerance. The primary outcome is effective exercise time (minutes) until interruption due to physical limitation or symptoms. Secondary outcomes include rating of perceived exertion, hemodynamic parameters, exercise enjoyment (PACES) and usability of the technology (SUS, intervention group only).

Discussion: This study will investigate whether VR can improve tolerance to aerobic exercise during hospitalization for HF, potentially providing preliminary evidence to guide the use of immersive technologies in cardiac rehabilitation. If benefits are observed, VR could be incorporated as a complementary tool to optimize adherence, motivation and safety in supervised exercise programs in this clinical context.

Trial registration: The trial was registered in the Brazilian Clinical Trials Registry (ReBEC), under the identifier RBR-4hrmkzz, on March 11, 2022.

Background: This protocol was developed to describe the design of a randomised controlled trial that will examine the clinical efficacy of a 4-week comparison of high-intensity vs. low-intensity physical training for people suffering from anxiety. The hypothesis is that the high-intensity group will have greater benefit in terms of reduced anxiety symptoms, improved physical health (blood pressure) and better adherence.

Methods: Thirty adults aged 18 to 70 years diagnosed with an anxiety disorder will be recruited for this study. Participants will be randomised into an intervention group (high-intensity training) and a control group (low-intensity training). Randomisation will be performed using counterbalanced block randomisation in a 1:1 ratio, stratified by sex. Both groups will perform 4 weeks of twice-weekly training supervised by an exercise physiologist. The primary outcome will be the total score on the Hospital Anxiety and Depression Scale (HADS) and the total score on the Beck Anxiety Inventory (BAI). The secondary outcomes include blood-pressure changes and adherence. Evaluations will be performed at baseline and following 4 weeks of the interventions, and 6 months after the termination of the intervention period (secondary endpoint).

Discussion: By investigating the clinical efficacy of a 4-week training intervention, we hope to provide applicable and generalisable knowledge about the efficacy of physical training for people suffering from anxiety disorders.

Trial registration: Clinical Trials NCT06881758 . Registered on 17 March 2025.