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Researchers are evaluating orelabrutinib, a brain-penetrating BTK inhibitor, in adults with Primary Progressive Multiple Sclerosis PPMS. This phase 3, randomized, double-blind, parallel-group, multicenter study compares orelabrutinib to placebo to assess its efficacy and safety in treating PPMS. About 705 participants aged 18 to 60 years will be enrolled globally with a 21 randomization favoring orelabrutinib. Participants will receive either oral orelabrutinib or a matching placebo. Treatment will last approximately 30 to 60 months, with a minimum of 12 months on study drug. The study includes two groups one receiving orelabrutinib and the other receiving placebo, both administered orally. The trial design is intended to monitor long-term effects and progression. During the study, participants will undergo regular assessments including disability progression measured over 12 weeks and up to approximately 120 weeks. Evaluations include MRI scans to monitor lesions, timed walking and hand function tests, cognitive testing, and safety assessments such as monitoring adverse events. The study will closely follow participants for up to 5 years to understand the impact of the treatment on disease progression and safety.

Researchers are evaluating the long-term safety and effectiveness of periodic adalimumab as an initial treatment for newly diagnosed Crohns disease CD patients. The study compares this approach to the standard step-up care that begins with corticosteroids. The goal is to improve treatment outcomes and reduce side effects by avoiding overtreatment, especially since current markers cannot predict disease progression at diagnosis. This trial addresses the limitations of existing therapies, such as delayed use of disease-modifying biologicals and risks associated with combination treatments. Participants are randomly assigned to one of two groups one receives episodic subcutaneous adalimumab monotherapy for 6 months as the first-line treatment, while the other follows the standard step-up care starting with corticosteroids. This study is a phase 4 trial that focuses on comparing these two treatment strategies over time, with detailed monitoring of drug effects and disease progression. During the study, participants will be closely monitored through clinical visits, imaging tests like ileo-colonoscopy and small bowel MRI or CT-enterography, and use of the myIBDcoach app for remote monitoring. Researchers will assess the number of yearly quarters of corticosteroid-free remission at week 96 as the primary outcome. Additional measures include bowel damage progression, adverse events, corticosteroid use, endoscopic remission, time to remission, quality of life, and healthcare costs. The total study duration includes assessments at weeks 24, 48, and 96 to capture both short- and long-term effects of the treatments.

Researchers are evaluating a special type of multisystemic therapy called MST-ID for adolescents aged 10 to 19 with severe behavioural problems living in families affected by intellectual disability ID. The study compares MST-ID to standard multisystemic therapy MST to see if MST-ID is better at reducing rule-breaking and other behavioural issues. The study uses both numbers-based assessments and families personal experiences to understand treatment effects and is sponsored by De Viersprong. The treatments involved are intensive, home-based therapies with 3 to 5 home visits each week over about three to five months. Both MST and MST-ID target adolescents behavioural problems by involving their family, school, and social environments. MST-ID differs by adapting its approach to the needs of families with ID, using simpler language, more structured sessions, and extra practice time to help families apply what they learn. Families receive either standard MST or the MST-ID specialization following usual referrals. Participants complete questionnaires at five time points start of treatment, end of treatment, and three follow-ups at 6, 12, and 18 months after treatment. Data collection includes standard MST monitoring and special interviews or discussions to capture families experiences. Researchers measure rule-breaking behaviour, other behavioural problems, parenting stress, out-of-home placements, school or work status, addictions, social networks, parenting skills, family relations, social support, and adolescent success with peers and education or work. The study lasts over 18 months with ongoing assessments to track impact.

Researchers are investigating whether taking breaks from the standard combination therapy of daratumumab, lenalidomide, and dexamethasone Dara-Rd for newly diagnosed multiple myeloma patients affects survival and quality of life. This study aims to compare continuous treatment versus planned treatment-free intervals to see if stopping therapy temporarily may reduce side effects, allow recovery from toxicity, and improve overall well-being while controlling the disease. Participants who have completed 12 cycles of Dara-Rd with at least a partial response and no signs of disease progression will be randomly assigned to one of two groups. One group will continue Dara-Rd therapy without interruption until disease progression, while the other group will stop treatment temporarily and restart it at biochemical progression, continuing until disease progression. The trial is open-label and will follow patients for several years to assess outcomes. Throughout the study, researchers will monitor participants event-free survival and progression-free survival for up to about 57 and 69 months, respectively. Additional assessments include side effect burden, patient-reported quality of life, treatment costs, treatment-free interval length, response times, and survival after second-line therapy. Regular evaluations will help determine how treatment interruption affects toxicity, dose intensity, and overall treatment outcomes over the long term.

Researchers are evaluating the effects of low-load blood flow restriction training LL-BFRT compared to heavy-load resistance training HLRT on graft maturity after anterior cruciate ligament ACL reconstruction using a bone-patellar tendon-bone graft. The study aims to understand whether LL-BFRT offers benefits or risks during rehabilitation by measuring MRI-based graft maturity as well as other factors like knee stability, range of motion, muscle strength, and patient satisfaction. Participants will be randomly assigned to one of two groups. The LL-BFRT group will perform biweekly strength training for 12 weeks starting two weeks after surgery, using a specialized tourniquet system to restrict blood flow during exercises such as leg press, leg extension, deadlift, and squats at 30% of their one-repetition maximum. The HLRT resistance training group will also train biweekly for 12 weeks, performing similar exercises but with heavier loads up to 70% of their one-repetition maximum without blood flow restriction. During the study, participants will be assessed at three and nine months after surgery with MRI scans to measure graft maturity and other evaluations including knee range of motion, stability, pain, function, muscle strength, and return to pre-injury sports level. Safety and feasibility of the rehabilitation methods will be monitored throughout. The total participation spans at least nine months to capture the main outcomes and recovery progress.

Researchers are evaluating an Integrated Oncological Decision-making Model IODM designed to tailor cancer treatment plans to individual patients. This study aims to assess how the IODM affects personalized treatment decisions and patient outcomes. The trial uses a stepped-wedge cluster randomized design involving 400 adult patients across eight oncological care paths in four medical centers in the Netherlands. Participants will receive either usual care based on standard clinical guidelines or care using the IODM, which integrates three components current oncological treatment options with their benefits and risks, the patients overall health including physical and emotional functioning, and the patients goals and preferences in treatment and daily life. The study transitions care paths from standard practice to the IODM in randomized steps. Throughout the study, researchers will assess the difference between standard treatment recommendations and actual decisions, focusing on whether these differences reflect more personalized choices. They will also evaluate patient quality of life, frailty, resilience, optimism, decision-making preferences, and patient-centeredness using questionnaires and medical records. The study duration includes the intervention and a 12-month follow-up, totaling around two years.

Researchers are investigating the effectiveness of adding liothyronine LT3 to levothyroxine LT4 treatment in patients with autoimmune hypothyroidism who continue to experience severe tiredness despite having normalized thyroid hormone levels on LT4 alone. This study addresses the problem that LT4 monotherapy may not fully replicate the natural balance of thyroid hormones, as healthy individuals produce some T3 directly. The trial also explores whether certain genetic factors influence response to combination therapy. The study begins with a run-in period where all participants switch to a standardized generic LT4 to stabilize thyroid hormone levels. After confirming normal TSH levels and persistent tiredness, participants enter a one-year randomized, double-blind trial comparing LT4LT3 combination therapy to LT4 with placebo. The LT4LT3 group takes LT4 once daily and LT3 twice daily at a set ratio. Visits occur at baseline and multiple times over the year to adjust doses and monitor health. Participants undergo physical exams, ECGs, blood tests, and complete questionnaires about tiredness, quality of life, and medical resource use throughout the study. Additional measures include bone markers, scans, cardiovascular and metabolic assessments, and neurocognitive tests in subgroups. The main outcome is the change in tiredness scores over 52 weeks, with safety and genetic factors also evaluated. The total study duration includes the run-in and treatment phases, lasting several months to over a year.

Researchers are investigating cachexia, a syndrome involving significant loss of body weight and muscle mass that affects cancer patients quality of life, survival, and treatment outcomes. The study aims to improve the accuracy of cachexia diagnosis by comparing self-reported weight changes with objective measurements taken before treatment. This pilot study involves patients aged 18 and older undergoing curative-intent chemotherapy or surgery for various cancers, including upper gastrointestinal, hepatobiliary, pancreatic, colorectal, and ovarian cancers. Participants will undergo extensive pre-treatment assessments including physical tests, body measurements, and laboratory tests. They will receive a weight scale and an accelerometer to measure daily body weight and physical activity at home. For chemotherapy patients, monitoring starts at initial clinic presentation, continues through treatment, and ends two weeks after chemotherapy. For surgical patients, monitoring pauses during hospital stay and resumes after discharge until follow-up. Imaging and body composition analyses will be performed before and after treatment. Throughout the study, researchers will record treatment-related adverse events, response to therapy, survival, and disease-free survival for up to five years. Physical activity, body composition, and other cachexia-related parameters will also be analyzed. Data will be collected via tests, scans, questionnaires, and equipment use, with adverse events classified by established criteria. This comprehensive monitoring aims to better understand cachexias impact and improve diagnosis accuracy in cancer care.

Researchers are evaluating the best rehabilitation method for patients who have suffered Displaced Intra-articular Calcaneal Fractures DIACFs, which are fractures involving the heel bone often requiring surgery. This study aims to compare two rehabilitation protocols Permissive Weight Bearing PWB and Restricted Weight Bearing RWB, focusing on functional outcomes, quality of life, radiographic differences, cost-effectiveness, and complications. The trial is a multi-center randomized controlled study involving patients aged 18 to 67 years who have undergone surgical fixation for DIACFs. Participants are randomly assigned to one of two rehabilitation groups. The PWB group starts weight bearing about two weeks post-surgery after wound healing, progressing according to patient comfort and pain with guidance from therapists and physicians. They follow milestones such as walking with crutches or canes with recordings of progress. The RWB group follows standard AO guidelines with 8 to 12 weeks of minimal weight bearing 0-10%, gradually increasing weight bearing by 25% weekly after 8 weeks. Both protocols include detailed records of weight bearing advice throughout treatment. During the study, participants will be assessed at 0, 2, 6, 12 weeks, and 6 months after surgery. Researchers will measure functional outcomes using the AOFAS questionnaire, foot function scores, daily living activities, quality of life surveys, and radiographic parameters like Bhlers angle. Costs and complications will also be tracked. Follow-up visits align with current trauma guidelines and include clinical evaluations and imaging, with radiation exposure consistent with standard care. The total study duration allows for comprehensive monitoring of recovery and rehabilitation effects.

Researchers are evaluating the effectiveness and safety of two combination treatments for adults with hormone receptor positive HR, human epidermal growth factor receptor 2 negative HER2- locally advanced or metastatic breast cancer that has a PIK3CA mutation. These patients have experienced recurrence or progression after treatment with a CDK46 inhibitor. This Phase 3, open-label, randomized study compares RLY-2608 zovegalisib plus fulvestrant against capivasertib plus fulvestrant to determine which treatment better controls the disease. Participants are assigned to one of two groups one group receives zovegalisib orally twice daily along with fulvestrant administered by injection on specific days during a 28-day treatment cycle the other group receives capivasertib orally twice daily on an intermittent weekly schedule plus fulvestrant injections on the same schedule. Treatment cycles repeat every 28 days. The study is conducted globally at multiple centers and continues until disease progression or other criteria are met. During the study, participants undergo regular assessments including scans reviewed by blinded independent central review to measure progression-free survival, as well as monitoring overall survival, response rates, quality of life questionnaires, and safety evaluations. Blood samples are taken periodically to measure drug levels. The study may last up to approximately 77 months for outcome measurements, with ongoing monitoring for adverse events and quality of life changes throughout this period.