Toxicity

Bipolar disorder (BD) is a serious mental illness that tends to run in families and affects behavior, thinking, emotions, social interactions, and work. It has characteristics like high prevalence, frequent recurrence, and early onset. Early recognition and diagnosis are challenging but important for better outcomes. This research aims to create a large, high-quality group of BD high-risk individuals by enrolling 400 participants over four years and following them intensively for ten years using an electronic mental health platform. The study will collect various types of data including clinical, genetic, cognitive, neuroimaging, sleep, EEG, eye movement, speech, facial expression, and movement to understand how biological, clinical, and environmental factors interact in BD onset. The study is observational and includes three groups: children aged 6 to 18 who have at least one parent with BD, children with atypical depression diagnosed by DSM-5 criteria, and healthy children matched by age and gender without psychiatric family history. Participants will be assessed yearly for four years, including brain scans and multiple follow-ups to track the development of mental illnesses, brain structure and function, cognitive function, sleep quality, quality of life, and genetic features. Participants will be involved in annual evaluations for four years, including clinical assessments and brain imaging. Researchers will monitor the differences in development among the three groups over time. The main outcomes focus on the prevalence of mental illness, brain development, and multi-modal feature changes. Secondary outcomes include cognitive function, sleep quality, quality of life, and genetic differences. This long-term follow-up aims to develop predictive models for BD onset and guide early, personalized interventions for those at high risk.

Researchers are studying the long-term risk of liver failure linked to TURALIO14 (pexidartinib) treatment in patients with symptomatic tenosynovial giant cell tumor (TGCT) who have severe symptoms or functional problems and cannot improve with surgery. This study also explores how liver damage happens by examining liver biopsy samples from patients who have or had liver toxicity while on TURALIO14. The goal is to understand liver injury mechanisms and assess safety over time. This is a non-interventional, observational study where no study medication is given. Participants have experienced liver test abnormalities from TURALIO14 treatment. Optional liver biopsies will be taken for detailed analysis of immune cells in the liver. Blood samples will also be collected to monitor liver function, safety, immune cells, and genetics. Participants will be followed yearly for up to 10 years to track liver health and potential failure after stopping TURALIO14. During the study, participants will provide blood samples and may choose to have a liver biopsy for further testing. Researchers will assess liver test results and monitor for signs of liver failure, liver transplant need, or death. Follow-up visits occur at least once per year for 10 years to observe long-term effects. The main outcome measured is how often liver failure occurs after stopping TURALIO14, helping to better understand long-term safety in this group.

Researchers are studying whether a new method of defining the radiation target areas can improve progression-free survival and reduce radiation complications in patients with high-grade glioma. This trial compares this new target delineation approach with the standard European Organisation for Research and Treatment of Cancer (EORTC) method. The goal is to see if the new method leads to better outcomes for patients after surgery. Participants will be randomly assigned to one of two groups. The trial group receives radiotherapy using the new target delineation scheme based on CT-MRI fusion images, with careful dose limits to protect sensitive brain areas. The control group receives radiotherapy following the EORTC target delineation method. Both groups receive temozolomide chemotherapy concurrently during radiotherapy at 75 mg/m² daily, followed by six cycles of adjusted temozolomide dosing after radiotherapy. During the study, participants will be monitored for progression-free survival up to three years after randomization. Researchers will also evaluate overall survival, quality of life using the EORTC QLQ-C30 questionnaire, and the incidence of radiation-related complications. Follow-up visits and assessments will continue through study completion to track these outcomes and ensure patient safety.

Researchers are evaluating whether giving the antibiotic meropenem in shorter but more frequent infusions can achieve similar blood levels compared to longer, less frequent infusions in intensive care unit (ICU) patients. The study aims to see if administering 1 gram six times daily in 15-minute infusions matches the serum concentration of the usual 2 grams three times daily in three-hour infusions. This pilot study focuses on optimizing antibiotic dosing to improve intravenous access time in critically ill patients. Participants will be randomly assigned to one of two groups: one receiving meropenem 1 gram six times daily through 15-minute infusions, and the other receiving 2 grams three times daily through three-hour infusions. The dosing will be adjusted based on daily kidney function monitoring. Blood samples will be collected at 24, 48, and 72 hours to measure antibiotic levels, and patients will be observed for side effects during treatment and for two days after. During the study, researchers will monitor serum meropenem concentrations to see if they stay above the minimum inhibitory concentration (MIC) for at least 50% of the time. Additional outcomes include days in the hospital, 30-day mortality after ICU admission, and serious side effects. The study involves daily blood tests and kidney function assessments, with the total study period running from 2021 to mid-2024. Patient safety and treatment adherence will be closely supervised throughout the trial.

This research aims to understand how changes in pupil size and reaction relate to the start of neurological side effects in patients receiving CAR-T cell therapy, specifically Axi-cel (CD19 CAR-T cell) treatment. It focuses on adults with certain types of lymphoma who are treated in a hospital setting. The study is observational and seeks to assess the connection between pupil changes and neurotoxicity within 10 days after treatment, along with evaluating the severity of symptoms and safety of the measuring device. Participants will have their pupils measured using the NeurOptics4 NPi4-300 Pupillometer, a handheld, non-invasive device that scans each eye separately without touching the eye. The scanning process takes less than five minutes per session. The study will track changes in the Neurological Pupil index (NPi) from before treatment to after infusion, and also assess differences between eyes to see if these relate to symptom severity. During the study, participants will undergo regular pupil measurements and be monitored for neurological symptoms using clinical evaluations and possibly imaging or EEG tests. Researchers will record any adverse events over about one year following study participation. The study will also assess the safety and ease of using the pupillometer device in this patient group. Participants will be involved throughout this monitoring period while receiving their usual care.

Researchers are studying whether fecal microbiota transplantation (FMT) can help treat gastrointestinal symptoms caused by chemotherapy or targeted therapy in patients with gastrointestinal cancers. This Phase 1 trial aims to evaluate the effect of FMT on the gastrointestinal tract in these patients, focusing on those with advanced gastrointestinal tumors. The goal is to understand how FMT might reduce side effects linked to cancer treatment. Participants are randomly assigned to one of two groups. The control group continues their usual chemotherapy or targeted therapy cycles every three weeks for five cycles, with treatment effectiveness assessed after every two cycles. The experimental group receives FMT starting from the fourth treatment cycle, with capsules containing donor gut bacteria given orally within three days before chemotherapy during the fourth, sixth, and eighth cycles. Each FMT dose includes about 40 grams of bacteria encapsulated into 120 capsules, taken over a short period during each treatment cycle. Throughout the study, patients undergo regular assessments to track gastrointestinal symptoms and gut microbiota changes. Researchers monitor the incidence and improvement of gastrointestinal side effects at 4 and 8 weeks after FMT. They also analyze gut microbiota diversity and its correlation with symptom improvement. Participants are followed during treatment cycles and for a post-treatment period to evaluate these outcomes, with safety and organ function closely observed.

Researchers are evaluating a pilot intervention aimed at reducing HIV and hepatitis C virus (HCV) transmission, as well as overdose risk behaviors, among people who inject drugs (PWID). The study uses a peer-driven approach targeting semi-public injection settings (SPIS) to promote safer practices. This intervention is grounded in social influence, social network, and social cognitive theories, focusing on improving communication and peer education to change social norms around risk behaviors. Participants will be randomly assigned to one of two groups: one receiving behavioral training with six sessions that include peer education and stocking of SPIS with risk reduction materials, and the other receiving an attention control (standard care). The intervention seeks to increase conversations about prevention and the availability of naloxone and other risk reduction materials in injection settings to reduce sharing of injection equipment and overdose risks. During the study, 120 index PWID participants will be selected based on their use of SPIS. Their involvement includes participation in the training sessions or control activities, with researchers monitoring overdose prevention and HIV/HCV prevention outcomes over six months. Assessments will include measures of overdose behaviors and related risk factors to evaluate how well the intervention influences these outcomes over time.

Researchers are studying whether an intensive approach to controlling high blood pressure is safe and more effective than standard treatment in lowering blood pressure and reducing the risk of heart damage during breast cancer treatment. This trial focuses on patients with breast cancer undergoing treatment with anthracycline-based chemotherapy and compares two systolic blood pressure (SBP) goals without testing specific medications. Participants are randomly assigned to one of two groups: one aiming for intensive blood pressure control with an SBP goal below 120 mm Hg, and the other aiming for standard control with an SBP goal below 140 mm Hg. Antihypertensive medications, including various types such as ACE inhibitors, beta-blockers, diuretics, and others, will be adjusted every 4 weeks for the first 3 months and then every 3 months up to 12 months. All participants receive dietary and lifestyle advice to help manage blood pressure. During the study, participants will have their blood pressure monitored at home and in clinic visits, along with echocardiograms at baseline, 6 months, and 12 months to assess heart function. Some participants may undergo cardiopulmonary exercise tests. Quality of life questionnaires and blood samples for biomarker analysis will also be collected. The main outcome measured is the change in systolic blood pressure from the start of the study to 12 months. The study lasts for one year, with regular follow-ups to evaluate treatment effects and safety.

Researchers are evaluating the safety and effectiveness of NT 201, a type of botulinum toxin A, compared with a placebo in adults who have moderate to severe platysma prominence, which refers to noticeable bands in the neck area. This Phase 3 study aims to understand how well NT 201 works and how safe it is for these participants. The study is sponsored by Merz Aesthetics GmbH and will be conducted in Europe. Participants will be randomly assigned to receive either a single injection of NT 201 or a matching placebo injection in the main study period (MP) on Day 1. After this period, those who received NT 201 can enter an open-label extension period (OLEX) where they will receive another injection of NT 201 on Day 1 of that phase. The study involves a double-blind design, meaning neither the participants nor the researchers know who receives the active drug or placebo during the main period. During the study, participants will be assessed using the Merz Aesthetics Platysma Scale - Dynamic (MAPS-D) to measure improvement in platysma prominence at various time points, including Week 2 and up to Week 17 in the main period. Both investigator and participant assessments will be used to evaluate the degree of improvement. Satisfaction questionnaires and global aesthetic improvement scales will also be used to measure participant satisfaction and aesthetic changes. Safety and efficacy will be closely monitored throughout the study, which lasts through the main and extension periods.

Researchers are studying the effects of local treatment on health and daily life in people with early-stage breast cancer in China. The focus is on those with stage I to III invasive breast cancer receiving surgery and other therapies before or after surgery. The study aims to understand both short- and long-term physical, emotional, and social effects of treatment, including tiredness, sleep problems, emotional distress, pain, and changes in heart or lung function, to improve recovery and quality of life. Participants will receive local therapy with curative intent, which may include surgery, chemotherapy, radiotherapy, endocrine therapy, or targeted therapy given before or after surgery. This observational study involves no experimental treatment. At the start, participants undergo clinical assessments, including heart and lung tests, lab work, and collection of blood and tissue samples. They also complete questionnaires about symptoms and well-being at multiple time points over five years. During the study, participants will complete surveys about their physical symptoms, emotional health, and quality of life at baseline, one week, one month, three months, six months, one year, and then annually up to five years. Researchers will monitor treatment-related toxicities and quality of life changes through these patient-reported outcomes. The study uses electronic data collection with quality checks to ensure accurate and consistent information for analysis and future research.