A Phase II, Randomized, Double-blinded, Placebo-controlled Trial of Liraglutide in Parkinson’s Disease

Status: 
Recruiting
Clinicaltrials.gov identifier: 
NCT02953665
Sponsor: 
Cedars-Sinai Medical Center
Enrollment: 
57
Study Design: 
This is a single center, double-blind, randomized placebo-controlled study. Subjects are randomized 2:1 to receive once daily self-administered injections of liraglutide (1.2 or 1.8 mg, as tolerated after a 2-week titration) or placebo at the same dose range. Participants will be followed for up to 56 weeks and will complete 9 in-person visits and 2 telephone visits. Eligible participants are those aged 25 to 85 with a diagnosis of idiopathic PD for at least 2 years. Notable exclusionary criteria include individuals with dementia (Mattis Dementia Rating Scale, MADRS-2, score <120), severe depression (BDI score > 29), Diabetes diagnosis, prior intracerebral surgical intervention, or current treatment with an anti-cholinergic medication.
Rationale: 
Primary Outcome Measures are: 1) change in motor function, determined by the change in MDS-UPDRS Part III scores at baseline, 28 and 54 weeks, 2) change in non-motor function determined by the change in Non-Motor Symptoms Scale (NMSS) score at baseline, 28 and 54 weeks, and 3) change in cognitive function, determined by the change in the MADRS-2 score at baseline, 28 and 54 weeks. Secondary Outcome Measures include: 1) change in peripheral insulin resistance, measured by the change in Homeostasis Model Assessment (HoMA-IR) index at baseline, 28 and 54 week visit, 2) change in the total MDS-UPDRS scores at baseline, 28 and 54 week visit, 3) change in quality of life determined by change in PDQ-39 scores at baseline, 28 and 54 weeks, 4) adverse events frequency, which will be monitored with vital signs, ECGs, urine and blood tests, at screening and follow-up visits.
Comments: 
Liraglutide has the advantage of being a re-purposed drug with established regulatory approval for Diabetes and obesity, and thus has an established safety and tolerability profile. Also similar between these two compounds is the demonstration of their neuroprotective effects in mouse models of PD, which proved superior to exenatide’s effects in these preclinical studies. A disadvantage of the drug is its once-daily injection, which will likely be less favorable to potential participants compared to exenatide and other once-weekly injected GLP-1 agonists under study (NLY01 and semaglutide).