Danon Disease

Researchers are studying the safety and effectiveness of RP-A501, a gene therapy using a modified virus to deliver the LAMP2B gene, in male patients 8 years and older with Danon Disease. This single-arm Phase 2 trial focuses on males who have a genetic variant of the LAMP2 gene and heart changes related to the disease. The goal is to understand how well this gene therapy works and how safe it is for this group of patients. Participants will receive one intravenous infusion of RP-A501, a gene therapy product made of a modified adeno-associated virus containing the human LAMP2B gene. This single dose is given during the treatment period, and patients are monitored over time to assess the therapy's effects. The study does not include a comparison group and focuses solely on this treatment. During the study, participants will be evaluated at regular intervals up to 60 months after infusion. Assessments include measuring LAMP2 protein expression in heart tissue, heart size and function via left ventricular mass index, and biomarkers indicating heart injury such as high sensitivity Troponin I and NT-proBNP. The study also tracks event-free survival and safety outcomes. Patients must be able to comply with study procedures and attend follow-up visits throughout the trial.

Researchers are evaluating the effects of a new herbal formulation called Melats P for women with Polycystic Ovarian Syndrome (PCOS), a common metabolic disorder affecting women of childbearing age. PCOS causes problems such as hormonal imbalance, irregular ovulation, infertility, obesity, excessive hair growth, acne, and metabolic issues like insulin resistance and type 2 diabetes. This study aims to compare the herbal formulation against conventional treatment and their combination in improving infertility and menstrual cycle regulation in women with PCOS. Participants will be divided into three groups: one receiving the herbal formulation Melats P at 500 mg twice daily, another receiving Metformin XR 750 mg twice daily, and a third group receiving both treatments together. Each treatment is given for 4 months. The herbal formulation contains plant-based ingredients chosen for their potential to restore hormonal balance and improve ovulation with fewer side effects compared to standard drugs. The study includes a phase 1 clinical trial design with randomized assignment and no masking. During the study, participants will have their menstrual cycle regulation monitored from baseline to 4 months. Additional assessments include blood tests for hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone, as well as metabolic measures like glycated hemoglobin (HbA1c), fasting insulin levels, insulin resistance (HOMA-IR), and body weight. These evaluations will occur at the start and after 4 months of treatment to assess safety and effectiveness. The total participation duration is approximately 4 months, with the study scheduled to start in February 2025 and end by March 2026.

Researchers are conducting an international observational study to understand the natural history of Danon disease, a rare and severe genetic heart condition caused by mutations in the LAMP2 gene. This study focuses on male patients aged 8 years and older and female patients aged 8 to 50 years. The goal is to gather detailed information on the disease's clinical course, symptoms, key events, and quality of life impact under current standard care. The study uses both retrospective and prospective data collection to build a comprehensive and long-term dataset. Participants are grouped into prospective and retrospective cohorts, with females in the prospective group requiring recent evidence of heart muscle thickening. No interventions are given, as the study observes natural disease progression. Some participants will serve as an external control group for comparison with another related trial. Participants will undergo regular assessments including heart imaging (echocardiograms), blood tests for cardiac biomarkers, ECGs, and physical function tests at 12, 24, and 36 months. Quality of life and heart failure status are also evaluated through questionnaires and clinical classifications. Researchers will monitor key outcomes like heart muscle mass, cardiac events, and survival. The study collects baseline labs and tracks anti-AAV9 antibody levels while following patients over years to better understand disease progression.

Researchers are evaluating the efficacy, safety, and tolerability of zeleciment rostudirsen (DYNE-251), given intravenously every 4 weeks, in ambulatory male children and adolescents aged 4 to 18 years with Duchenne muscular dystrophy (DMD) who have a specific mutation suitable for exon 51 skipping. This Phase 3 study aims to provide important information about this treatment option for this group of patients with DMD. The study includes three distinct periods: a Screening period lasting up to 6 weeks, a Placebo-Controlled Period of 72 weeks where participants are randomly assigned to receive either zeleciment rostudirsen or placebo every 4 weeks, and an open-label Long-Term Extension Period of up to 96 weeks during which all participants receive the study drug every 4 weeks. This design allows researchers to compare the treatment to placebo and then assess longer-term effects. Participants will be closely monitored throughout the study with regular assessments including the primary outcome of Rise From Floor (RFF) velocity measured at baseline and Week 73. Various secondary measures such as walking speed, stair climbing ability, lung function, patient global impressions, blood creatine kinase levels, and safety through adverse event monitoring and blood drug levels will be collected up to Week 169 or study completion. The total study duration including the extension is up to approximately 168 weeks. This thorough evaluation helps understand the treatment’s impact and safety over time.

Researchers are conducting a multi-centre observational study focused on children with rare inherited cardiac conditions, particularly those diagnosed with cardiomyopathy before age 16. The study aims to better understand the genetic and environmental factors influencing these heart muscle diseases, including disease progression and response to treatments. By collecting genetic information and clinical data, the study seeks to identify new personalized treatment options for affected children. Participants include children with diagnosed inherited cardiac conditions and their parents. The study collects baseline demographic, imaging, and genotyping data primarily from routine clinical care, including whole genome sequencing. Some participants may provide blood or saliva samples for genetic and biomarker analysis. Family members of deceased patients might also donate stored tissue or samples if available. The study plans to follow participants over a 5-year period. During the study, researchers will access clinical data including health information and results from routine tests like echocardiograms. Some procedures may involve minimal risk, such as blood or saliva collection. The study focuses on monitoring the participants' health outcomes and genetic markers to understand disease progression. The total follow-up duration for each participant is up to five years, with data collected throughout this period.

Researchers are evaluating a new family health communication tool called Let's Get REAL designed to increase youth involvement in real-time decisions about stem cell transplant and cellular therapy (SCTCT). This pilot trial focuses on pediatric patients aged 8 to 17 years who are referred for SCTCT due to malignant or nonmalignant disorders. The study aims to assess the feasibility, acceptability, and appropriateness of this communication tool in helping families discuss treatment decisions. Participants, including youth in two age groups (8-12 and 13-17 years) and their parents, will receive the Let's Get REAL tool to use up to one month before their SCTCT consultation visit. They will complete surveys before using the tool, up to one month after the consultation, and up to one month post-discharge from SCTCT. The consultation visits will be audio-recorded, and participants may opt to take part in a semi-structured interview within eight weeks after the consultation. During the study, participants will provide demographic and baseline information and complete several questionnaires measuring decision-making involvement, anxiety, communication, and satisfaction. Researchers will analyze both quantitative survey data and qualitative feedback to evaluate the tool's impact. The total study participation spans from before the consultation through up to eight weeks after, with ongoing monitoring of youth-parent communication and decision-making processes.

Researchers are evaluating new advanced heart scan techniques using Cardiac Magnetic Resonance (CMR) imaging to improve diagnosis and risk assessment for people with rare heart muscle diseases, called rare cardiomyopathies. These diseases cause changes to the heart muscle that make it harder to pump blood, and are often hard to diagnose and manage. The study aims to better identify these conditions and predict future heart risks to enable more personalized care. The study uses novel CMR imaging biomarkers such as T1/T2 Mapping for tissue characterization, Extracellular Volume Fraction to detect tissue changes, Feature Tracking Strain Analysis for subtle heart muscle function, and refined Late Gadolinium Enhancement patterns to more accurately show scarring or infiltration. These techniques go beyond standard heart scans and may help diagnose rare cardiomyopathies like cardiac amyloidosis, Fabry disease, Danon disease, and Noonan disease. Participants will undergo CMR scans using these advanced methods. Participants who join will have their heart imaged with these specialized CMR scans. The researchers will collect data on outcomes such as overall survival, cardiovascular death, heart transplantation, hospitalizations, and device implantations over 2 to 15 years. This will help track disease progression and evaluate the predictive value of the new imaging methods. The study is observational and aims to improve diagnosis, risk prediction, and management for people with rare cardiomyopathies.

Researchers are collecting important medical information to better understand several ultra-rare Glycogen Storage Diseases (GSDs), including types 0a, 0b, VII, X, XII, XIII, XV, PRKAG2 syndrome, and Danon disease. The goal is to build a detailed natural history database that describes these rare diseases to help guide future treatment strategies. Participants include individuals diagnosed with these rare GSDs, and data will be gathered from multiple sources to capture the full clinical course of each condition. This observational study does not involve any treatment or intervention. Instead, it focuses on collecting data from medical records retrospectively and prospectively. The study is conducted at Duke University but includes participants receiving care elsewhere. Researchers will review medical charts over time to gather clinical, laboratory, biochemical, and imaging information relevant to the participants' conditions. Participants will have their medical records continually reviewed throughout the study, which is expected to last an average of 10 years. Data collected will include demographics, diagnostic details, biopsy results, medical and family history, system reviews, and laboratory tests related to liver, muscle, nerve function, as well as urine and blood tests. The main outcome measured is the progression of the disease as confirmed by ongoing medical record review.

This research aims to collect CD34+ hematopoietic stem cells (HSC), mononuclear cells, and granulocytes from peripheral blood and bone marrow of adults. These cells will be used in laboratory studies and clinical treatments to develop new cell therapies for patients with inherited or acquired immune or blood disorders. Both healthy adult volunteers and adult patients with primary immune deficiencies or blood disorders may participate to support research and clinical therapy development. Most participants will undergo daily injections of granulocyte colony stimulating factor (G-CSF) for 5 to 6 days to help move HSC into the blood, followed by apheresis collection. Some patients may have bone marrow collected through aspiration or harvesting for clinical or research use. Mononuclear cells and granulocytes may be collected from blood with or without pre-treatment using G-CSF and dexamethasone. Collected cells are used for gene therapy development, cell engineering, and laboratory studies to understand disease mechanisms and improve treatments. Participants will be involved in cell collection procedures such as apheresis or bone marrow aspiration. Researchers will monitor cell mobilization and collection success, perform laboratory studies on the collected cells, and store samples for future research or clinical use. The study tracks outcomes including cell mobilization, collection, and laboratory research results. Participants may contribute to ongoing development of gene therapies or cellular treatments under separate approved protocols.

Calciphylaxis, also called uremic calcifying arteriolopathy (UCA), is a rare condition causing painful skin lesions due to small blood vessel calcification and clotting. This disease mainly affects patients with end-stage renal disease (ESRD) who require hemodialysis. Researchers are evaluating the safety and effectiveness of adding rheopheresis, a special blood filtration treatment, to the standard care for calciphylaxis in these patients through a prospective randomized controlled trial. In this study, participants will be randomly assigned to one of two groups. The experimental group will receive rheopheresis in addition to standard care, involving an induction phase of 3 sessions in the first week followed by 2 sessions weekly for 3 weeks, then a maintenance phase with 1 session per week up to week 11. The comparator group will receive sham-apheresis sessions on the same schedule, which mimics the procedure without actual filtration. Rheopheresis uses a machine to remove certain high molecular weight proteins from plasma to help treat microcirculation problems. Participants will be followed for 12 weeks during treatment with regular assessments of wound healing, pain levels, quality of life, antibiotic usage, hospital discharge days, survival, and inflammatory protein changes. The primary outcome is the percentage of patients achieving complete healing of calciphylaxis lesions after 12 weeks. Secondary outcomes include partial healing, new lesion occurrence, pain and analgesic use, and overall survival at 12 weeks and one year. Safety and efficacy data will help determine the added value of rheopheresis in calciphylaxis care.