Phase 2 Trial Assesses Felodipine Tolerability for Huntington's Disease
核心洞察
A Phase 2 clinical trial (FELL-HD) is underway to evaluate the tolerability of felodipine in patients with early-stage Huntington's Disease (HD).
The open-label, dose-finding study will enroll 18 participants aged 35-70 with genetically confirmed HD to test three different doses of felodipine over 58 weeks.
The primary outcome is the number of adverse events, with secondary outcomes including quality of life, cognitive and motor function, and biomarker changes.
A Phase 2 clinical trial, FELL-HD, is currently investigating the tolerability of felodipine in individuals with Huntington's Disease (HD). The study, published in the British Medical Journal, aims to determine the safety and tolerability of felodipine, a drug approved for hypertension, in early-stage HD patients.
The single-center, open-label, dose-finding trial plans to enroll 18 participants between 35 and 70 years old who have genetically confirmed HD and are exhibiting early clinical features of the disease. Participants will be administered one of three escalating doses of felodipine over a 58-week period, followed by a 4-week follow-up.
The dosing regimen involves an initial dose of 2.5 mg for two weeks for all participants. Subsequently, the first group will receive 5 mg of felodipine until week 58. The second group will receive 5 mg for two weeks, followed by 10 mg until week 58. The third group will receive 5 mg for two weeks after the initial 2.5 mg, then 5 mg for two weeks, 10 mg for two weeks, and finally 20 mg until week 58. Doses will be reduced if not tolerated, reverting to the last tolerated dose.
The primary outcome measure is the number of adverse events associated with felodipine administration. Secondary outcome measures include assessments of quality-of-life scales, cognitive and motor function, non-motor symptoms, and peripheral and central disease biomarkers, evaluated through brain magnetic resonance imaging (MRI).
An associated sample study, FELL HD-s, will analyze blood and cerebrospinal fluid samples to further investigate the drug's effects. Huntington's Disease is characterized by the accumulation of mutant huntingtin (HTT (搜索)) protein within neurons, leading to cellular toxicity. Preclinical research suggests that autophagy, a cellular process for degrading toxic proteins, plays a crucial role in mitigating the effects of mutant HTT.
Felodipine has demonstrated strong autophagy-inducing properties in preclinical models of HD, making it a potential therapeutic candidate. This trial will provide critical data on its tolerability and potential efficacy in humans with Huntington's Disease.