GLP1R in Parkinson's Disease (GIPD)

Brief Summary:
The purpose of the study is to test the neuroprotective and anti-inflammatory properties of semaglutide in idiopathic Parkinson's disease (PD)

Detailed Description:
The trial is a single center, double-blind, placebo-controlled study. We plan to enroll 270 newly diagnosed patents with idiopathic Parkinson's disease (PD) over 2 years. The subjects that are enrolled in the study will be randomised to receive once a week self-administered subcutaneous injections of semaglutide (1.0 mg) or placebo in a 1:1 study design.

Semaglutide has been approved by the Food and Drug Administration (FDA) and European Medicines Agency to treat adults with type 2 diabetes. The treatment has not been approved for use in patients with PD. Semaglutide is a synthetic analogue of glucagon-like peptide 1 (GLP1), which stimulates GLP1 receptors (GLP1R). Stimulation of GLP1R in B-cells in the pancreas potentiates insulin secretion and contribute to blood glucose regulation. In the brain it is known that GLP1R stimulation in the hypothalamus contribute to appetite and body weight regulation. Besides these known GLP1R effects, GLP1R can inhibit production of pro-inflammatory cytokines in microglia, which in turn will stop/slow down degeneration of neurons in the brain. Another GLP1 agonist, exenatide, has been tested in patients with PD, showing significant improvement of motor symptoms. However, it could not be concluded whether this was caused by an symptomatic or neuroprotective effect.

Eligible participants will be treated with semaglutide or placebo for 24 months in a double blind period 1 of the study. Thereafter both groups will receive semaglutide for another 2 years in an open period 2 of the study. The study will measure effects of semaglutide on motor symptoms (assessed by changes in the MDS-UPDRS part III, and in levo-dopa equivalents), on nigrostriatal degeneration (assessed by changes in DAT-scan uptake), on cognitive function (assessed by MME and MOCA, on quality of life (assessed by EQFDQ, PDQ) and on non-motor symptoms of PD (assessed by NMSS).The tests will be performed at baseline, after 12, 24, 36 and 48 months of the study. Blood and cerebrospinal samples will be taken to analyse inflammatory markers, and to confirm penetration of semaglutide across the blood brain barrier.


Study Type: Interventional  (Clinical Trial)
Estimated Enrollment: 120 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: delayed start design
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of GLPIR Stimulation on Neuroprotection and Inflammation in Parkinson's Disease
Estimated Study Start Date: January 2, 2019
Estimated Primary Completion Date: December 31, 2024
Estimated Study Completion Date: December 31, 2024

Arms:
- Active Comparator: semaglutide
- Placebo Comparator: placebo