Stroke survivors frequently experience long-lasting motor impairments of the upper limb that limit their independence and quality of life. While recovery is most pronounced in the early phases, targeted rehabilitation can still promote meaningful improvements in the chronic stage by stimulating neuroplasticity. Immersive virtual reality and myoelectric control interfaces can deliver intensive, engaging, task-specific training, while cerebellar non-invasive stimulation has shown potential to enhance motor recovery. This trial investigates whether combining cerebellar intermittent theta burst stimulation with personalized virtual reality training, with assistance provided through myoelectric control, can improve upper limb function in patients with chronic stroke. This study is a randomized, controlled, parallel-group trial with three arms. Forty-five participants with chronic stroke will be randomly assigned to (1) active cerebellar intermittent theta burst stimulation followed by assisted myoelectric control virtual reality training, (2) sham stimulation with the same virtual reality training, or (3) conventional physical therapy. Each participant will receive twelve 30-min sessions over 4 weeks. Assisted myoelectric control uses surface electromyographic signals from residual muscle activity to drive movements in the virtual environment. An adaptive algorithm provides corrective assistance by moving a virtual end-effector according to the projection of the patient’s electromyographic activity onto more physiological activation patterns and gradually reducing support as performance improves. The primary outcome is upper limb motor function, assessed with the Fugl-Meyer Assessment for Upper Extremity. Secondary outcomes include tests of manual dexterity, functional independence, electromyographic activity, and corticospinal excitability. Assessments will be conducted at baseline, immediately after the last session of intervention, and at 6-week follow-up by blinded evaluators. This trial is the first to systematically test the combined effect of cerebellar stimulation and physiologically grounded myoelectric assistance within an immersive virtual reality setting. By integrating top-down neuromodulation of cerebello-cortical circuits with bottom-up task-specific feedback, the approach aims to optimize neural plasticity and promote motor recovery beyond standard therapy. If effective, the intervention could provide a novel and personalized rehabilitation strategy for chronic stroke survivors. ClinicalTrials.gov NCT06911671. Registered on 3 February 2023.
Mindfulness-based cognitive therapy (MBCT) is a group intervention recommended by NICE for adults who have experienced recurrent depression but is untested for adolescents. MBCT aims to teach people to recognise early indicators of depression, to avoid repetitive thinking patterns that make relapse more likely, and to respond to stressors in ways that protect mental health. We developed Mindfulness for Adolescents and Carers (MAC), a version of MBCT adapted to be more engaging for young people. MAC includes a parallel programme aimed at strengthening family support and parental mental health and may help minimise the developmental impact of functional impairment during the transition to adulthood. The primary aim of this trial is to evaluate the clinical- and cost-effectiveness of MAC in 15- to 18-year-olds at risk of repeated depressive episodes in the UK. ATTEND will be a two-arm, pragmatic, parallel-group, superiority, individually randomised controlled hybrid type I trial of clinical and cost-effectiveness. We will randomise 480 15SAP-18-year-olds who have received at least one previous evidence-based intervention for depression or anxiety, yet continue to experience symptoms of depression, to either MAC plus treatment as usual (TAU) or TAU alone. MAC will be delivered by trained professional facilitators to groups of 6 to 14 young people, with a parallel but optional group for parents/carers. The primary outcome will use an area under analysis of the mean difference in the Short Mood and Feelings Questionnaire, which will be collected fortnightly over a 12-month follow-up period. Secondary outcomes will be measured in both young people and their parents/carers, including depression, anxiety symptoms, quality of and coping with life, and the quality of parent-child relationships at baselines, 14 weeks and 12 months post randomisation. Parental mental health will also be measured fortnightly. After the primary main and mediation analyses have been completed, the de-identified individualised patient data, data dictionaries and statistical analysis code underlying published results will be as accessible to other researchers with a methodologically sound proposal via the ATTEND Core Team using the standard ATTEND Publication Proforma. The protocol and statistical analysis plans will also be available via the study website. This study will provide important information about whether MAC is a clinically and cost-effective intervention to reduce depression symptom severity and chronicity in adolescents. International Standard Randomised Controlled Trials, identifier: ISRCTN 17687131. Registered on 15 August 2024.
Head and neck cancer surgery is associated with substantial physiological stress and functional decline, particularly in patients with compromised nutritional status, reduced exercise capacity and psychological distress. Although Enhanced Recovery After Surgery (ERAS) protocols have improved perioperative outcomes in head and neck oncology, they primarily target intra- and postoperative care and do not adequately address preoperative deficits in functional reserve. Prehabilitation aims to optimise physical, nutritional and psychological health before surgery and may complement ERAS pathways; however, evidence supporting a combined prehabilitation and ERAS approach in head and neck cancer surgery remains limited, especially in non-Western populations. This study is a prospective, stratified, open-label randomised controlled trial conducted at a tertiary cancer centre. Adult patients aged 18–70 years with carcinoma of the buccal mucosa scheduled for elective segmental mandibulectomy will be screened for eligibility and enrolled following informed consent. Participants will be randomised to receive either standard perioperative care or a combined prehabilitation plus ERAS programme, using permuted block randomisation with stratification based on type of reconstruction (free flap or pedicled flap). The intervention group will undergo a minimum of 2 weeks of structured prehabilitation prior to surgery. This will include optimisation of chronic medical conditions, nutritional assessment using Subjective Global Assessment with targeted dietary counselling and supplementation, correction of anaemia, preoperative speech and swallowing therapy, psychological interventions incorporating cognitive behavioural and motivational strategies, and a personalised home-based exercise and respiratory physiotherapy programme. Exercise prescriptions will address jaw mobility, cervical range of motion, shoulder function and aerobic capacity. Both groups will receive perioperative care according to institutional practice, with the intervention arm additionally receiving standardised ERAS components across preoperative, intraoperative and postoperative phases. The primary outcome is postoperative length of hospital stay. Secondary outcomes include major postoperative morbidity, readmissions, functional capacity, speech and swallowing outcomes, biochemical parameters and behavioural changes. All analyses will follow the intention-to-treat principle. This PREERA outlines the rationale and methodology of a multimodal perioperative strategy integrating prehabilitation with ERAS in head and neck cancer surgery. The study aims to inform future perioperative care models and larger definitive trials. Clinical Trials Registry of India (CTRI): CTRI/2026/01/100326. Date of registration: 5 January 2026 (prospectively registered).
The exact disease-causing mechanisms in ALS remain incompletely understood. A possible cause is inflammation of neurons. Compared to other neurodegenerative diseases, neuroinflammation is pronounced in ALS, presumably leading to disease progression and neuronal death. Patients with ALS can have neuronal autoantibodies and most notably antibody-producing cells in the cerebrospinal fluid. The CD20-binding therapeutic antibody rituximab targets these antibody-producing B-cells. Rituximab is a medication commonly used in neurology. Single patients with ALS have already been treated with rituximab, which was well tolerated. We therefore want to evaluate safety and efficacy of a treatment with rituximab in ALS patients in a double-blind placebo-controlled trial. With this trial we aim for slower disease progression and unveiling disease-causing mechanisms in ALS. A total of 52 male and female patients older than 18 years with active sporadic ALS and disease duration of less than 24 months who are on a stable dose of riluzole (50 mg BID) should be included. Patients requiring assisted ventilation of any kind or have a known intolerance to the study medication rituximab are excluded. The study medication rituximab or placebo should be administered over a period of 52 weeks at 4 distinct time points, followed by a follow-up period of 79 weeks with 4 visits. Treatment efficacy should be evaluated using the ALS functioning scale ALSFRS-R-SE at every study visit (except safety visits). Safety will be assessed through regular laboratory analyses, adverse event (AE) and serious adverse event (SAE) monitoring, and CD20+ B-cell kinetics. The primary endpoint is the change in the ALS Functional Rating Scale-Revised (ALSFRS-R-SE) from baseline to week 79. Trial sites will be at Charité/DZNE Berlin and DZNE Bonn. ALS is a rapidly progressive neurodegenerative disease with limited treatment options. Recent preclinical in vivo studies suggest that B-cell-mediated autoimmunity contributes to disease progression. This trial will evaluate whether rituximab, which specifically depletes CD20+ B-cells, can slow ALS progression and provide insights into disease mechanisms. The trial was registered in the German WHO-recognized primary register Deutsches Register Klinische Studien DRKS (German Clinical Trials Register) on 3/07/2023 under registration number DRKS00030948.
Ensuring inclusivity in clinical research has become both a scientific and ethical imperative. Representative participation in clinical studies is essential for greater generalizability and equitable applicability of research findings. Persistent exclusion of underserved (US) and underrepresented (UR) groups in clinical studies continues despite ongoing regulatory efforts across Europe and beyond to address this issue. Yet ambiguity persists around how US/UR populations are defined, limiting progress towards achieving more representative, inclusive and equitable clinical research. This review aims to understand how US/UR populations in European clinical studies are presented in literature, identify common descriptors and definitions, and examine which groups are labeled as US/UR in order to inform efforts to enhance inclusion and equitable representation of these populations in research. A narrative literature review with a systematic approach was conducted, in line with PRISMA guidelines. PubMed and Psycinfo/PsycArticles databases were searched for articles published between 2014 and 2024, including characterizations of US/UR populations in European clinical studies, yielding 5413 articles. Data were extracted on definitions, descriptors, and identified US/UR populations within clinical research, with attention to geographic context and barriers to inclusion. Following screening, 62 full-text publications were included. Most articles reported findings from the U.K. (n = 29) or from international contexts (n = 20), while only five articles focused on EU countries. About one-third of the reviewed articles (n = 21) provided some definitions/descriptions of US/UR populations, whereas most relied on descriptors or group examples. Race and ethnicity were the most frequently cited descriptors followed by socioeconomic status (SES), age, geographic location, health status, disability, language, sex, and gender. Across clinical studies, several recurring groups emerged, that were organized in four overarching categories: demographic, socioeconomic and geographic, health-status and access-related, and those shaped by contextual or systemic exclusion. The findings of this review point to a clear gap in the current literature regarding explicit characterizations of US/UR populations in clinical studies in Europe. Current ways of describing these groups lack contextual grounding and consistent application, limiting their usefulness for promoting data-driven inclusivity. To this aim, context-specific characterizations and adherence to reporting standards are needed to guide equitable representation in clinical research. This review informs the IHI READI consortium’s mission and efforts to foster a more representative, inclusive and patient-centered European research ecosystem.
