Alcohol use disorder (AUD) is a prevalent, chronic condition generating considerable global morbidity, mortality and socioeconomic burden. Despite the availability of established pharmacotherapies, overall treatment uptake remains low and effect sizes are moderate at best. Emerging evidence highlights substantial differences in treatment response between sexes and genders, yet these factors are rarely systematically considered in clinical trials or routine care. Existing reviews have limited scope and often exclude gender-diverse populations. This project aims to (1) Synthesise evidence on gender- and sex-specific efficacy, safety and adherence in AUD pharmacotherapies, (2) Evaluate the consideration of sex and gender beyond binary classifications in existing research and (3) Develop recommendations for gender- and sex-sensitive treatment strategies.

A systematic review and meta-analysis will be conducted using (PubMed, Web of Science, Scopus, Google Scholar, German Clinical Trials Register and ClinicalTrials.gov). We will include randomised controlled trials of pharmacotherapies for AUD with a minimum treatment duration of 4 weeks, reporting gender-specific and/or sex-specific results. The literature search will cover studies published up to October 2025, with inclusion restricted to articles published in English or German, regardless of setting. Two reviewers will independently screen records and assess risk of bias (Cochrane RoB), with evidence certainty evaluated using Grading of Recommendations Assessment, Development and Evaluation and aligned to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 and Sex and Gender Equity in Research guidelines.

Ethics approval is not required as only data from already completed studies and supplementary information directly provided by study authors are used. Findings and recommendations will be disseminated in peer-reviewed journals and presented at conferences and workshops.

CRD420251079160.

Post-COVID-19 syndrome, defined by persistent symptoms lasting beyond 12 weeks of a SARS-CoV-2 infection, affects both severe and mild COVID-19 cases. Fatigue is the most common symptom, impacting 58% of patients. Other symptoms include mental symptoms, cardiovascular and respiratory issues and autonomic dysfunction. Chronic inflammation and immune dysregulation seem to be associated with post-COVID-19 fatigue. Despite its impact on healthcare and the economy, effective treatments are limited. Yoga and health education have been shown to be effective for fatigue in other related conditions. The aim of this study, therefore, is to investigate the efficacy, safety and cost-effectiveness of yoga and health education on post-COVID-19 persistent fatigue.

A randomised controlled trial with 100 patients with persistent fatigue due to post-COVID-19 syndrome is being conducted at three study centres. Patients are randomised to two interventions, yoga and health education. Both interventions include 12 weeks of 90 min supervised group sessions and 60 min of home practice per week. The primary outcome measure is fatigue on the Chalder Fatigue Scale 12 weeks after randomisation. Secondary outcome measures include postexertional malaise (DePaul Symptom Questionnaire), health-related quality of life (Short Form Health Survey-12 Item Version, EuroQol 5-Dimension 5-Level Questionnaire), anxiety, depression (Hospital Anxiety and Depression Scale), stress (Perceived Stress Scale), sleep quality (Pittsburgh Sleep Quality Index), hand grip strength, laboratory parameters and adverse events. Physical activity analysis over 7 days using a body-worn sensor and 24-hour heart rate variability using a 3-channel ECG recorder are assessed exploratively. All outcome measures will be assessed 12 and 24 weeks after randomisation. In addition, health economic analyses as well as mediator and moderator analyses including self-reported body awareness, self-efficacy, personality traits and treatment credibility/expectations will be conducted. Furthermore, qualitative interviews at week 12 will be carried out.

The trial received ethical approval from the Ethics Committee of the University Hospital Tübingen (approval number: 775/2022BO2). Results will be disseminated via peer-reviewed open-access publications, scientific conferences and targeted communication to patient organisations, healthcare providers and the wider public.

NCT05890599.

Combined vascular endothelial growth factor/programmed death-ligand 1 blockade through atezolizumab/bevacizumab (A/B) is the current standard of care in advanced hepatocellular carcinoma (HCC). A/B substantially improved objective response rates compared with tyrosine kinase inhibitor sorafenib; however, a majority of patients will still not respond to A/B. Strong scientific rationale and emerging clinical data suggest that faecal microbiota transfer (FMT) may improve antitumour immune response on PD-(L)1 blockade. Early trials in melanoma with FMT and reinduction of immune checkpoint blockade (ICI) therapy in patients with anti-PD-1-refractory metastatic melanoma were reported in 2021 and demonstrated reinstatement of response to ICI therapy in many patients. Due to anatomical vicinity and the physiological relevance of the gut-liver axis, we hypothesise HCC to be a particularly attractive cancer entity to further assess a potential benefit of FMT in combination with ICI towards increased antitumour immunity. Additionally, HCC often occurs in patients with liver cirrhosis, where liver function is prognostically relevant. There is evidence that FMT may increase hepatic function and therefore could positively affect outcome in this patient population.

This prospective, multicentre, randomised, placebo-controlled, double-blind phase II clinical trial has been designed to assess immunogenicity and safety of FMT via INTESTIFIX 001 combined with A/B in advanced HCC in comparison to A/B with placebo. Primary endpoints are measured as tumour CD8+ T cell infiltration after 2 cycles of treatment with vancomycin, A/B+INTESTIFIX 001 in comparison to vancomycin-placebo, A/B+INTESTIFIX 001-placebo and safety of the therapeutic combination in advanced HCC. INTESTIFIX 001 is an encapsulated FMT preparation by healthy donors with a high alpha-diversity in their gut microbiome for oral administration, manufactured by the Cologne Microbiota Bank (CMB). Sample size was calculated to achieve a specific expected accuracy for the primary immunological endpoint. 48 subjects will be randomised to reach a goal of 42 usable measurements in the modified intention-to-treat set. Subjects will be randomised in a 2:1 ratio to A/B or placebo (28 A/B, 14 placebo).

The study was approved by ethics committee review and the German Federal Ministry of Drugs and Medical Devices. The trial is registered under EU CT no. 2023-506887-15-00. The outcome of the study will be disseminated via peer-reviewed publications and at international conferences.

NCT05690048.

Prostate cancer (PCa) is the second most common cancer in men worldwide and genetic factors and family history significantly increase the risk of PCa. Men at increased risk for PCa often experience higher PCa-specific anxiety and distress. Comprehensive prevention strategies for men with familial or genetic PCa predisposition are lacking. Consequently, the psychological impact, facilitators and barriers for risk-adapted PCa prevention lack comprehensive study. The novel prospective registry and prevention clinic ‘ProFam-Risk’ (prevention clinic for familial PCa risk) at the University Hospital Düsseldorf offers personalised risk assessment and risk-adapted prevention recommendations for men with familial or genetic PCa predisposition. As part of this research project, this study (‘ProFam-Psych’ - risk-adapted prevention clinic for familial and genetic prostate cancer: psychosocial effects; funded by German Cancer Aid) aims to evaluate the longitudinal psychosocial trajectories associated with this novel prevention clinic.

In a longitudinal observational mixed-methods design, psychosocial outcomes will be assessed in participants of the prevention clinic (case group, CAG) and compared with urology patients without increased risk for PCa (control group, COG). Psychosocial outcomes will be collected at four time points in the CAG (T0: baseline; T1: after first visit; T2: after risk stratification consultation; T3: follow-up 6 months after T2) and at two time points in the COG (T0: baseline during inpatient stay; T1: post-inpatient stay). Recruitment started in 2023, and the recruitment target is n=225 participants (CAG) and n=118 participants (COG). Primary endpoint is the longitudinal course of PCa-specific anxiety (Memorial Anxiety Questionnaire for Prostate Cancer) in the CAG. Secondary endpoints include the comparison of T0 and T1 outcomes between the CAG and COG and the assessment of changes in perceived PCa risk and perceived personal control in the CAG. To assess facilitators and barriers to participation in the risk-adapted PCa prevention clinic, a minimum of n=12 semi-structured qualitative interviews will be conducted, with recruitment continuing until data saturation is reached. Qualitative data will be analysed using qualitative content analysis.

Ethics approval from the Medical Faculty of the Heinrich Heine University Düsseldorf was obtained (2023-2551). Results of the main objective and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.

DRKS.de, DRKS00032350. Prospectively registered with the German Clinical Trials Register (DRKS) on 14 September 2023.