Prader-Willi Syndrome

Researchers are studying CSTI-500 in people aged 13 to 50 years who have genetically confirmed Prader-Willi Syndrome (PWS). This phase 2, open-label, dose-escalation study aims to evaluate the safety, tolerability, how the drug moves through the body, and its effects. The study focuses on monitoring treatment-emergent adverse events and other clinical parameters to better understand CSTI-500's impact in this population. Participants will receive CSTI-500 taken by mouth in increasing doses guided by blood level measurements to individualize treatment. There are three dose groups targeting low, medium, and high exposure levels of CSTI-500. The study does not use a placebo and all participants know the treatment they receive. The dosing and monitoring occur over a planned 12 to 14 week period. During the trial, participants will have regular safety evaluations including laboratory tests, ECGs, vital signs, and assessments of behavior and hyperphagia symptoms using standardized questionnaires. Caregivers are involved in providing information and supporting adherence. The primary outcomes include adverse event incidence and target drug levels achieved, while secondary outcomes measure changes in clinical global impression and behavior scales over 12 weeks. Overall participation lasts several months with close monitoring throughout.

Researchers are evaluating the effectiveness and safety of pitolisant in treating excessive daytime sleepiness (EDS) in patients aged 6 years and older with Prader-Willi syndrome. This Phase 3, randomized, double-blind, placebo-controlled, global study also aims to assess how pitolisant affects irritable and disruptive behaviors, hyperphagia, and other behavioral problems such as social withdrawal, stereotypic behavior, hyperactivity, noncompliance, and inappropriate speech. The study includes up to a 45-day screening and baseline period followed by a double-blind treatment phase where participants are randomly assigned to receive either pitolisant tablets or placebo once daily in the morning. In-person visits occur on Days 29, 57, and 77 during this period. Afterward, participants may choose to enter an optional open-label extension period with pitolisant, which includes visits on Days 113, 260, and 441. Follow-up visits are scheduled 15 and 30 days after the final dose in both the double-blind and extension phases. Participants will be closely monitored through various assessments including patient-reported sleep impairment scales, caregiver and clinical impressions of sleepiness and behavior, and questionnaires measuring hyperphagia and other behavioral issues. Safety is monitored by tracking treatment-emergent adverse events throughout the study. The total participation duration may extend over a year for those in the open-label extension, with multiple visits and follow-ups to evaluate the study outcomes comprehensively.

Researchers are studying RM-718 to assess its safety, tolerability, and how the body processes it in healthy individuals with obesity and in patients with impairments in the MC4R pathway. This study includes people aged 12 to 65 years and focuses on those with hypothalamic obesity and Prader-Willi Syndrome, conditions related to obesity caused by specific brain or genetic issues. The study has four parts: Part A tests single weekly doses of RM-718 or placebo in healthy obese adults aged 18 to 55; Part B tests multiple weekly doses in a similar group; Part C involves multiple weekly doses in patients aged 12 to 65 with hypothalamic obesity; and Part D gives multiple weekly doses to patients with Prader-Willi Syndrome aged 12 to 65. Doses are administered by weekly injections under the skin, and parts A and B are randomized, placebo-controlled, and double-blind, while parts C and D are open-label dose escalations. Participants will receive various weekly doses of RM-718 or placebo depending on their study part, with monitoring for side effects throughout. Researchers will assess safety by tracking adverse events during and after treatment, as well as measure how the drug behaves in the body over time. They will also monitor changes in body mass index, weight, waist size, and hunger symptoms in patients with hypothalamic obesity and Prader-Willi Syndrome. The study includes safety follow-up calls extending up to 210 days after dosing in some parts, with total participation lasting up to 26 weeks depending on the group.

Cerebral palsy (CP) is a condition caused by brain injury in babies that affects movement and muscle tone. Some children with CP may have other developmental challenges like learning difficulties, but many have mostly motor skill issues. This study aims to reduce the age at which CP is diagnosed by using new and specific assessments in high-risk infants, such as those born prematurely or with brain injuries. It also seeks to better predict which children might need support for learning, language, or other developmental outcomes. The research is coordinated by University College Cork and supported by Research Ireland and the Cerebral Palsy Foundation, USA. The study compares two groups: a high-risk group of infants with factors like prematurity or hypoxic-ischaemic encephalopathy, and a control group of healthy term infants who did not require neonatal intensive care. Participants will be assessed in outpatient clinics using novel examinations to track their development. The study will take place at multiple hospitals in Ireland and will monitor infants from near term up to 24 months corrected gestational age. During the study, infants will have regular assessments at various time points, including near term to 4 months corrected gestational age, birth to 6 weeks, and 4 to 24 months. Researchers will evaluate motor and intellectual outcomes over a five-year period with follow-ups at 4 and 18 months. Guardians will provide consent and comply with study requirements, and the team will observe the infants' progress to better understand early signs of CP and developmental impairments.

Prader-Willi Syndrome (PWS) is a rare genetic neurodevelopmental disorder caused by damage in the 15q11-q13 region leading to hypothalamic dysfunction. People with PWS often show challenges in social interaction, intellectual difficulties, serious eating disorders, mood problems, and sensory features linked to autism. The CASSPER study investigates the unique autistic and sensory profiles in children with PWS and examines how early treatment with oxytocin might affect these symptoms, addressing the need for early and personalized care in this population. Children aged 3 to 16 years with genetically confirmed PWS participate in this observational study. They will undergo psychological and sensory tests, including questionnaires and sensory evaluations. The study focuses on assessing autistic symptoms, sensory profiles, cognitive-behavioral disorders, and the impact of early oxytocin treatment in younger children. These assessments take place during planned hospital visits or multidisciplinary consultations at the study centers. Participants will be evaluated over a short period, from day 1 to day 3, with researchers measuring autistic symptom prevalence, sensory characteristics, and their relationship with behavioral disorders and family quality of life. The study also compares these factors in children treated early with oxytocin versus those untreated. This approach aims to improve understanding of autistic traits in genetic neurodevelopmental disorders and support better care strategies for children with PWS.

Researchers are studying how a noninvasive brain stimulation technique called repetitive transcranial magnetic stimulation (rTMS) might affect hunger and feelings of fullness in people with Prader-Willi syndrome. This condition is associated with severe overeating, and the study aims to understand how stimulating a specific brain area, the cerebellum, may impact these symptoms. The study is sponsored by Brigham and Women's Hospital and involves adults aged 18 to 64 years. Participants will receive daily targeted rTMS treatments to the cerebellum for one week. This procedure uses a magnetic coil held by the scalp to create a magnetic field that temporarily changes brain activity. The rTMS method used, called intermittent theta burst stimulation (iTBS), is designed to modulate brain circuits linked to appetite control. During the study, participants will be monitored at baseline and then again one week after the rTMS treatment to measure brain responses using BOLD imaging and to assess retention in study assessments. Researchers will also track how long it takes to enroll subjects over the course of up to 18 months. The study does not involve masking or placebo and focuses on understanding brain function related to hyperphagia in Prader-Willi syndrome.

Researchers are conducting the Collaboration for Down Syndrome Progress (CDP), a long-term observational study that follows people with Down syndrome across all ages. The study aims to better understand the health, development, and everyday experiences of individuals with Down syndrome over time. It collects consistent data across multiple sites to learn why certain health conditions are more common in this population and how to improve their care and quality of life. Participants complete standardized assessments including medical history, neurobehavioral evaluations, physical exams, and review of health records. Biological samples such as blood, saliva, and tongue swabs are collected to study genetics and other biological markers. Optional activities include sleep studies, activity monitoring with wearable devices, brain imaging using MRI, and metabolic and endocrine tests. These data and samples are stored and shared with researchers to support future studies. Participants and their caregivers provide information through questionnaires and clinical assessments at multiple visits. The study monitors enrollment over four years and collects data to track health and developmental changes. Optional subsample studies allow for deeper evaluation in areas like sleep, movement, brain structure, and metabolism. The study ensures data privacy and aims to advance understanding of co-occurring health issues in Down syndrome to guide better clinical care and research.

Researchers are evaluating the effects of auricular vagal neuromodulation therapy (aVNT) on adults with Prader-Willi Syndrome (PWS), a rare neurodevelopmental disorder. The study aims to assess how daily aVNT stimulation impacts emotional control, executive functions such as planning and flexibility, hyperphagia, depression, and quality of life. This is the first multicenter randomized controlled trial exploring aVNT as a treatment for PWS, which currently has no therapies addressing its many behavioral and cognitive challenges. Participants will be randomly assigned to receive either active or sham aVNT stimulation using a small portable device with electrodes placed on the left ear. The stimulation sessions last four hours per day, seven days a week, over nine months. The device delivers painless electrical microcurrents to stimulate the auricular branch of the vagus nerve. Active stimulation is adjusted by participants for comfort and occurs during relaxing activities. The sham group uses the same device but with stimulation applied to an area without vagus nerve fibers. During the study, emotional control will be measured every two weeks for eleven months, including before and after the stimulation period. Other outcomes like executive functioning, hyperphagia, depression, and quality of life will be assessed four times: before treatment, and at three, six, and nine months. Participants and their caregivers will be involved in evaluations. The study includes safety monitoring and aims to understand the persistence of effects after stimulation ends.

Researchers are studying how high-intensity interval training (HIIT) affects brain function and molecular pathways related to weight control in adults aged 18 to 70 years. This study includes people with a body mass index over 19, including those who have had bariatric surgery and experienced significant weight regain. The goal is to better understand how exercise influences brain activity and appetite, which could help future obesity treatments. Participants will undergo a 12-week HIIT program with four weekly sessions lasting 28 minutes each. Each session includes a 3-minute warm-up, six cycles of 40 seconds of high-intensity exercise followed by 3 minutes of moderate intensity, and a 3-minute cool-down. These sessions will be supervised and partly conducted at a diabetes center and at home. Before and after the training, participants will complete clinical visits involving medical assessments and brain imaging. During six clinical visits, participants will have tests including blood draws, glucose tolerance tests, metabolic rate measurements, exercise capacity tests, psychometric evaluations, and functional brain MRI scans. Researchers will track changes in brain connectivity, appetite, mood, cognitive function, and molecular markers in blood samples before and after the exercise program. The study will monitor participants' progress and gather data to understand the effects of HIIT on brain and weight regulation.

Scientific knowledge about how children's thinking skills help them control their appetite is limited. This research aims to provide new directions for preventing obesity by studying how cognitive development influences young children's ability to make healthy food choices and eat in moderation. The study focuses on preschoolers aged 4 to 6 years and their primary caregivers to better understand these processes during early childhood. Participants will take part in observational tasks that measure general executive functioning and eating-specific executive functioning. These tasks involve presenting different food and non-food items and recording how children respond to instructions. The study will develop new ways to measure top-down appetite self-regulation and examine its relationship with children's eating behavior, weight status, and food parenting practices. During the study, children will complete one or two visits over two weeks where researchers assess food choices, eating behavior without hunger, and body mass index z-scores. Caregivers will also provide information about feeding responsibility. The study will collect detailed data to better understand how cognitive factors relate to healthy eating and weight in preschoolers, with all assessments completed within a short timeframe.