Umbrella Clinical Trial to Evaluate Repurposed Compounds in Rett Syndrome
Abstract
Objectives and Rationale: The proposed study will evaluate several U.S. Food and Drug Administration (FDA)-approved drugs as re-purposed treatment options for patients with Rett Syndrome (RTT). RTT is a rare, devastating neurodevelopmental disorder (NDD) affecting 1 in 10,000 females at birth. There are no treatments available for RTT, so there is a tremendous unmet need. Recruitment into trials can be challenging without specialized centers and patient advocacy organization involvement. There are two primary objectives of this study: (1) Determine if the three agents (ketamine, donepezil, and vorinostat) are safe, tolerated, and show signs of efficacy in girls with RT, and (2) determine if performing an umbrella trial is efficient and feasible in RTT as a rare disease. There is significant rationale to propose this work. The three drugs being studied have strong preclinical data and mechanistic rationale for RTT, providing strong justification to put these compounds forward in RTT. Second, the oncology and COVID fields have demonstrated that platform trial designs are efficient and feasible, therefore, we believe that this same approach will be successful in a rare disease like RTT. Finally, two of the drugs to be tested were identified through novel high throughput screening platforms that could be used for other neurological disorders if validated. This trial will test the efficiency of the platforms. Topic Area and Strategic Goal: RTT is a Fiscal Year 2022 Peer Reviewed Medical Research Program (PRMRP) Neuroscience Topic Area. This proposal will focus on the PRMRP Strategic Goal of Treatment: Evaluation of repurposed drugs to determine whether they are safe and efficacious to improve the health and quality of life in individuals living with RTT. Applicability and Impact of the Research: The proposed clinical trial will demonstrate whether the drugs under review have safety and utility in RTT and the approach through which these drugs were identified has utility for many central nervous system (CNS) disorders. This work will also illustrate that a rare condition, such as RTT, can be efficiently studied using an umbrella protocol design minimizing the demand on the patient community. The outcome of the proposed clinical trial could have broader implications for individuals living with chronic conditions such as Parkinson s Disease, Alzheimer s Disease, and other more prevalent CNS disorders. Types of Patients: Participants in the research study will be recruited from existing clinic patient populations. Each of the clinical sites participating in this trial also serve military families from local bases. If the drugs being evaluated through the proposed clinical trial are found to be safe and effective treatment options for people living with RTT, that patient population stands to benefit greatly from these findings. In addition, the data and outcomes produced by this study could benefit a countless number of individuals living with other rare and common neurological disorders. This could benefit the military population because of the prevalence of certain neurological disorders among active-duty and Veteran military members. Potential Clinical Applications and Benefits: The clinical application of this study is demonstrating the effectiveness of this platform approach in rare diseases. This study will also demonstrate that the three drugs are safe in RTT and have signals of efficacy. If true, then working with our industry partners, we will launch further studies on these agents with the goal of improving the lives of individuals with RTT. Lastly, validating the drug-screening platforms that brought the donepezil and vorinostat to the trial could be used to identify compounds for other disorders like depression, posttraumatic stress disorder, and other neurological disorders. This would be of benefit to the military population because of the prevalence of these conditions among active
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310864
Entities
People
- Jeffrey Neul
Organizations
- United States Army
- Vanderbilt University