Study to Evaluate the Effect of Lixisenatide in Patient With Parkinson's Disease
Condition: Parkinson Disease
MeSH terms: Parkinson Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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).
    

Intervention name(s): Lixisenatide; placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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; Patients randomized in the placebo group will receive the corresponding placebo administered subcutaneously (once daily subcutaneous injection).
Other intervention name(s): injection drug; placebo injection
Intervention MeSH terms: Lixisenatide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment