Status:
Recruiting
Clinicaltrials.gov identifier:
Sponsor:
University Hospital, Toulouse
Enrollment:
158
Study Design:
This is a multi-center randomized double-blind placebo-controlled proof-of-concept Phase 2 trial. It is a 2-arm study, with participants randomized 1:1 to either lixisenatide or placebo. The Lixisenatide group will receive lixisenatide 10μg/day for 14 days and then 20μg/day, administered via once-daily subcutaneous injections for 12 months. Participants unable to tolerate the 20μg/day dose can have their dose reduced to 10μg/day. After 12 months of treatment period there will be a 2-month wash-out period.
The study includes individuals aged 40 to 75 years who have early-stage PD, defined as PD diagnosis for less than 3 years without dyskinesias or motor fluctuations. Participants must have an optimized and stable PD medication regimen, including dopamine agonist, levodopa, and/or MAO B-inhibitor) for one month prior to the baseline study assessment. Participants are expected to remain on their medication regimen for at least the first 6 months, and ideally the full 12 months, of the study. Notably, individuals will be excluded from participation if they have had previous GLP-1 agonist exposure, have participated in another interventional trial within 30 days, or have had surgical intervention for Parkinson’s. Medical conditions that prevent participation include major depression, cognitive impairment (MoCA score <26), Type 1 or 2 Diabetes, have had a weight change more than 5kg in 3 months prior to screening, hyperthyroidism or uncontrolled hypothyroidism.
Rationale:
The Primary Outcome Measure is the change from baseline to end-point (month 12) in the MDS-UPDRS Part III motor sub-score, evaluated in the “ON” state.
Comments:
A distinct advantage of lixisenatide is that it is a repurposed drug, rather than a novel compound. As it is FDA-approved for Diabetes, it has a well-established safety and tolerability in humans. The aforementioned preclinical work in neurodegenerative and Parkinson’s models suggests that lixisenatide may be more effective than exenatide at engaging the GLP-1R target, reducing inflammation and promoting neuroprotection. An advantage of this study design for participants is that they do not have to be treatment naive; they can be on a stable Parkinson’s medication regimen during study participation. A disadvantage for participants is that the drug is administered as daily injections, as compared to weekly injections for other compounds (exenatide, NLY01 and semaglutide).
