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Researchers are evaluating whether taking antipsychotic medication every other day is as effective as taking it daily for people diagnosed with schizophrenia spectrum or other psychotic disorders. This phase 4 trial aims to compare the usual daily dosing with an "extended" dosing schedule, where medication is taken one day on and one day off. The study also investigates whether this alternate dosing reduces side effects and improves overall wellbeing and functioning. Participants will be randomly assigned to either continue their usual daily antipsychotic treatment or switch to the alternate day dosing. The drugs studied include Risperidone, Olanzapine, and Paliperidone, with doses adjusted to individual needs and provided in capsules that maintain blinding. The trial lasts for one year, with study visits every two weeks during the first six months and every four weeks during the last six months, totaling 22 visits. During the study, participants will be regularly assessed using clinical rating scales and monitored for side effects, wellbeing, and functioning. The main outcome measure is clinical deterioration, evaluated at the start and after 52 weeks using the Brief Psychiatric Rating Scale - Expanded. Medication adherence, side effect frequency and severity, and symptom changes will be closely tracked throughout the trial to compare the two dosing schedules.

Researchers are investigating the drug bezuclastinib in an open-label, two-part Phase 2 study for patients with Advanced Systemic Mastocytosis (AdvSM), including Aggressive Systemic Mastocytosis (ASM), Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN), and Mast Cell Leukemia (MCL). The study aims to evaluate the safety, effectiveness, and how the drug behaves in the body for these serious conditions. Bezuclastinib is given orally as tablets taken continuously in 28-day cycles. The study has two parts: Part I focuses on identifying safe and tolerable doses of bezuclastinib over 18 months, while Part II evaluates its effectiveness by measuring the objective response rate and confirming the relationship between drug exposure and response during another 18-month period. Participants will undergo assessments including clinical evaluations, laboratory tests, and monitoring of their disease status to determine treatment effects and safety. Researchers will track the drug's impact on the disease and patient health throughout the study, which involves continuous treatment and follow-up over the specified time frames.

Researchers are investigating treatment options for patients with favorable-risk prostate cancer, which includes those with low to favorable intermediate risk disease. The study explores combining two advanced radiation therapies, stereotactic ablative body radiotherapy (SABR) and high-dose rate (HDR) brachytherapy, to potentially improve convenience, reduce side effects and costs, and maintain excellent cancer control. This phase 2/3 trial aims to assess the tolerability and outcomes of delivering one MR-guided HDR treatment along with one SABR treatment, rather than the traditional multiple HDR fractions. The treatment plan includes a single SABR session delivering 13.5 Gy to the whole prostate and seminal vesicles, followed about 1-3 weeks later by one HDR brachytherapy fraction delivering 13.5 Gy to the prostate and less than 20 Gy to MRI-visible lesions. Before treatment, patients undergo planning CT, mpMRI imaging, and insertion of gold seed markers for precise targeting. Biobanking of urine, blood, and biopsy tissue is done before and after treatments. Imaging and dosimetric parameters are recorded at each step to ensure accurate delivery. Participants are closely monitored throughout the study with assessments of urinary, rectal, and sexual function at baseline and multiple follow-up points up to five years. Toxicities are evaluated at 6, 12, 24 weeks, and later at 9 months, 24 months, and every six months thereafter. Blood tests measuring PSA and testosterone levels, as well as quality of life questionnaires, are collected regularly. This comprehensive follow-up helps researchers measure both short-term and long-term effects of the combined treatment approach.

This research evaluates the use of inhaled Methoxyflurane to reduce pain and anxiety during intrauterine device (IUD) insertion, a common contraceptive procedure often causing moderate to severe pain, especially in individuals who have not given birth. The study focuses on female patients aged 18 to 55 undergoing IUD insertion and aims to improve patient satisfaction with pain management through a Phase 4 randomized controlled trial. Methoxyflurane is a short-acting, self-administered inhaled analgesic that has shown rapid and effective pain relief in acute and procedural settings without requiring intravenous access or prolonged recovery. Participants receive either 3 mL of inhaled Methoxyflurane delivered via a handheld Penthrox inhaler or 3 mL of normal saline as a placebo through an identical inhaler in a double-blind, placebo-controlled design. Methoxyflurane allows patients to control their dosing and is non-narcotic, making it suitable for short outpatient procedures like IUD insertion. The trial compares the effects of Methoxyflurane and placebo on pain and anxiety during the procedure. During the study, patient satisfaction with pain management is the primary outcome, measured by pain intensity 20 minutes after the procedure. Secondary outcomes include anxiety levels and monitoring for any adverse events such as dizziness or headache. Participants must be able to use the inhaler device and will receive a cervical block during the insertion. The study includes assessments before and after IUD insertion to evaluate pain, anxiety, and safety over the course of the procedure.

Preterm birth before 37 weeks' gestation is common and linked to many health challenges, especially when it occurs before 29 weeks. At this early stage, infants often face breathing difficulties due to immature lungs, sometimes requiring resuscitation. This study aims to compare two oxygen concentrations, 30% and 60%, used during resuscitation of very preterm infants to determine which leads to better survival and neurodevelopmental outcomes by about two years of age. The study uses a cluster randomized crossover design, where hospitals alternate between using 30% and 60% oxygen to resuscitate infants born between 23 and 28 weeks gestation. Infants receive the assigned oxygen concentration for the first 5 minutes after birth, with adjustments made based on oxygen saturation levels to maintain safe ranges. The intervention lasts 10 minutes, including initial resuscitation and oxygen titration to stabilize the infant. Participants will be closely monitored during their hospital stay and followed up at 24 months corrected age to assess survival and major neurodevelopmental outcomes. Data collected will include oxygen saturation, heart rate during resuscitation, and longer-term health measures. The study's results aim to guide safer oxygen use in resuscitating extremely preterm infants worldwide.

Researchers are studying the effects of deep brain stimulation (DBS) on brain function in patients with various neurological and psychiatric disorders, such as Parkinson's disease, essential tremor, dystonia, depression, epilepsy, neuropathic pain, and Alzheimer's disease. DBS is a treatment that targets specific brain circuits, and this study aims to use advanced MRI techniques to better understand how DBS influences brain anatomy and function. The study uses functional MRI (fMRI) to evaluate brain activity changes associated with DBS and to explore whether fMRI can improve clinical care for these patients. Participants in this prospective cohort study include adults aged 18 to 85 who are either planning to undergo DBS electrode placement or have already received it. The study involves performing various MRI scans, including structural MRI at 1.5 or 3 Tesla and functional MRI scans during resting state and tasks. Patients with externalized leads or internalized implantable pulse generators (IPG) will be scanned with the DBS device either switched off or on. The fMRI results will be analyzed to observe brain responses to different DBS settings and shared with clinicians to help optimize DBS programming. Throughout the study, participants will undergo MRI scans before and after DBS implantation, with follow-up lasting up to one year. Researchers will measure brain areas activated by DBS using fMRI and assess changes over time. The study requires participants to understand the research purpose and provide informed consent. Safety evaluations and post-operative follow-up will help determine the potential role of MRI in enhancing DBS treatment outcomes.

Researchers are assessing the safety and effects of Ritlecitinib, a study medicine, for treating hidradenitis suppurativa (HS), a condition causing long-lasting, painful red skin lumps. This phase 2 study focuses on adults with moderate to severe HS who have not responded well to or cannot tolerate antibiotics. The goal is to compare experiences and outcomes between those receiving Ritlecitinib and those receiving a placebo. Participants will be randomly assigned to take either Ritlecitinib or a placebo pill once daily at home. The treatment involves an initial loading dose of Ritlecitinib for 8 weeks, followed by an 8-week maintenance dose, totaling 16 weeks of treatment. The placebo group will receive a matching pill with no active medicine. Over approximately 24 weeks, including screening and follow-up, participants will attend around 10 clinic visits for health evaluations, including physical exams, blood and urine tests, vital signs, chest X-rays, ECGs, hearing tests, and questionnaires. They will also track their medication intake and HS symptoms daily using an electronic diary on a mobile phone. The study will measure how many patients achieve at least a 50% improvement in HS symptoms by week 16 to evaluate treatment response and safety.

Researchers are evaluating MDNA11, a long-acting "beta-only" recombinant interleukin-2 designed to activate immune cells that attack cancer while minimizing stimulation of cells that suppress immunity. This Phase 1/2 open-label study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and early anti-tumor activity of MDNA11 alone or combined with pembrolizumab in patients with advanced or metastatic solid tumors. The study includes dose-escalation and dose-expansion parts for both monotherapy and combination therapy with pembrolizumab. MDNA11 is given intravenously every two weeks with doses ranging from 0.003 to 0.6 mg/kg for monotherapy, while dose ranges for combination therapy are also evaluated. Treatment continues until progression, withdrawal, or loss to follow-up, with tumor assessments by CT or MRI every 8 weeks. Participants will undergo regular imaging scans every 8 weeks to monitor tumor response and safety assessments throughout the 24-month study. Researchers will track recommended doses for expansion, treatment-related adverse events, and overall safety. The study involves up to 115 patients across multiple sites and includes long-term monitoring for up to 24 months.

Researchers are evaluating whether an investigational drug called OHB-607 can prevent Bronchopulmonary Dysplasia (BPD), a common chronic lung disease, in extremely premature infants. The study compares infants receiving OHB-607 alongside standard neonatal care to those receiving standard care alone to reduce the burden of this lung condition. This is a Phase 2b, multicenter, randomized, open-label study focused on safety and clinical efficacy. Participants will receive an intravenous infusion of OHB-607 from birth until reaching a postmenstrual age (PMA) of 29 weeks and 6 days. The study includes two arms: one group receives the investigational drug plus standard care, while the other group receives only standard neonatal care. The treatment period ends at 29 weeks plus 6 days PMA, after which infants are monitored. Throughout the study, researchers will track the incidence of severe BPD or death up to 36 weeks PMA, whichever occurs first. Assessments will include clinical evaluations and monitoring for safety and any side effects. The study also involves long-term follow-up to observe the infants' health outcomes beyond the treatment period. Participation involves consent from parents and collection of birth and medical history information.

Researchers are evaluating new treatment options for adults with locally advanced or metastatic colorectal cancer that cannot be removed by surgery and has a specific KRAS G12C gene mutation. This study compares the safety and effectiveness of adding calderasib and cetuximab, both targeted therapies, to a standard chemotherapy regimen called mFOLFOX6. The goal is to see if this combination can help patients live longer without their cancer growing or spreading compared to current treatments that may include mFOLFOX6 with or without bevacizumab. The study has two parts. It involves treatment with calderasib taken as an oral tablet, cetuximab given according to standard procedures, and mFOLFOX6 chemotherapy combining oxaliplatin, leucovorin/levofolinate calcium, and 5-fluorouracil. Some participants may receive bevacizumab or a bevacizumab biosimilar as part of the comparison. The treatments are given following approved dosing schedules. This design allows researchers to assess the safety and tolerability of these drug combinations in treating this type of colorectal cancer with the KRAS G12C mutation. Participants will be monitored for side effects, treatment tolerability, and cancer progression over a period that may last up to about 44 months. Researchers will track outcomes such as how many participants experience dose-limiting toxicities or adverse events, how many stop treatment due to side effects, and progression-free survival time. Assessments include health evaluations, laboratory tests, and imaging to observe cancer status. This long-term follow-up aims to understand both safety and effectiveness of the treatment combinations.