Study to Evaluate the Effect of Lixisenatide in Patient With Parkinson's Disease (LixiPark)
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|ClinicalTrials.gov Identifier: NCT03439943|
Recruitment Status : Recruiting
First Posted : February 20, 2018
Last Update Posted : July 30, 2018
|Condition or disease||Intervention/treatment||Phase|
|Parkinson Disease||Drug: Lixisenatide Drug: placebo||Phase 2|
This study will be a French, multicenter parallel groups, 2-arm, randomized, placebo-controlled, double-blind, proof-of-concept (POC) phase II trial evaluating the effect of lixisenatide, in patients with early PD.
The treatment period will be followed by a wash-out period of 2 months.
JUSTIFICATION/CONTEXT Parkinson's disease (PD) is a common neurodegenerative disease. Currently available symptomatic treatments allow improving motor and to a lesser extent non-motor function in PD patients.
None of these treatments can slow down the underlining disease process and the relentless progression of motor and non-motor disability.
Several mechanisms including the aggregation of misfolded alphasynuclein, mitochondrial dysfunction, oxidative stress and neuroinflammation have been related to the pathogenesis of PD. Recent evidence further suggests the implication of cerebral insulin resistance in the neurodegenerative process, while glucagon-like peptide 1 receptor (GLP1-R) agonists that are approved for the treatment of type 2 diabetes have neuroprotective properties in animal models of PD (Aviles-Olmos et al., 2013a). Moreover, the results of a recent clinical pilot trial suggest that treatment with the GLP-1R agonist exenatide for 12 months improves motor function in patients with moderate PD . GLP1-R are widely expressed in the central nervous system and GLP1-R agonists such as liraglutide, lixisenatide and exenatide have measurable brain concentrations, which makes them suitable for treating brain disorders.
Lixisenatide is a well-tolerated GLP-1R agonist that can be administered once-daily (subcutaneous injection). It has demonstrated positive effects on learning and memory through an increase of hippocampal neurogenesis in preclinical models of obesity/diabetes. Furthermore, lixisenatide increases neurogenesis and decreases microglial activation in rodent models of Alzheimer's disease (APPswe/PS1ΔE9 mice and Aβ25-35 rats) (. At the same dose, lixisenatide showed higher effectiveness at activating brain GLP-1R than liraglutide and exenatide, and showed more effective neuroprotection in a variety of in-vitro models of neurodegeneration (WO2013/030409A1).
Thus, this randomized, double-blind, clinical trial now aim to evaluate the effects of lixisenatide, versus placebo, on both motor and non-motor PD symptoms in patients at an early stage of PD.
This study will involve centers of the French national Parkinson's disease and movement disorders research network (Ns-Park network).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||158 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Multicenter, Randomised, Placebo-controlled, Double Blinded, Parallel Arm Proof-of-concept Trial of Lixisenatide in Patients With Early Parkinson's Disease|
|Actual Study Start Date :||June 13, 2018|
|Estimated Primary Completion Date :||September 2021|
|Estimated Study Completion Date :||December 2021|
Lixisenatide (10μg/d for 14 days and then 20μg/d): once daily subcutaneous
Patients randomized in the Lixisenatide group will receive 10μg/day for 14 days and then 20μg/day administered by once-daily subcutaneous injections during 12 months. If patients are unable to tolerable the dose of 20μg/day, this dose can be reduced to 10μg/day
Other Name: injection drug
Placebo Comparator: Placebo
Placebo: once daily subcutaneous injection
Patients randomized in the placebo group will receive the corresponding placebo administered subcutaneously (once daily subcutaneous injection).
Other Name: placebo injection
- Change from baseline to end-point (M12) in the MDS-UPDRS III motor ( Movement Disorder Society-Unified Parkinson's disease rating scale) [ Time Frame: 12 month ]
The main objective of the study is to evaluate the effect of lixisenatide (20 μg/d), versus placebo, administered as add-on therapy with the usual antiparkinsonian treatment, on the progression of motor disability in patients with early PD in order to assess its potential "disease-modifying" effect.
The primary endpoint of this study is the change from baseline to end-point (M12) in the MDS-UPDRS III motor examination score, evaluated in the best ON condition in patients with early Parkinson's Disease.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03439943
|Contact: Olivier. RASCOL, MD, PHD||05 61 14 59 62 ext email@example.com|
|Contact: Wassilios MEISSNER, MD, PHD||05 57 82 12 53 ext firstname.lastname@example.org|
|Principal Investigator:||Olivier. RASCOL, MD, PHD||University Hospital, Toulouse|