The development of a disease-modifying therapy that delays, reverses or stops the symptom progression remains the most important unmet goal in the treatment of Parkinson's disease (PD). Apart from its glucose lowering effect, glucagon-like peptide-1 (GLP-1) receptor stimulation has been investigated in animal models of PD and shown to increase neurogenesis, to arrest and possible reverse nigrostriatal damage, and to protect dopaminergic neurons from neurodegeneration. Exenatide is a synthetic analogue of human GLP-1, resistant to the metabolic processes that degrade it in its naturally occurring form. Results from a recent randomised, double-blind, placebo-controlled trial in PD showed that patients in active treatment for one year were improved compared to the placebo arm with regard to their performance in Movement Disorders Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor subscale in the practically defined OFF medication state. The aim of this trial is to investigate the effect of Exenatide, 2 mg, subcutaneous injection, once weekly on disease progression represented by the change in longitudinal Positron emission tomography with 2-deoxy-2-\[fluorine-18\]fluoro- D-glucose (FDG-PET) in individual PD subjects, and to identify an Exenatide-related pattern in FDG-PET that will provide insight into the treatment-effect in the brain. The investigators chose the standard regimen prescribed in Type 2 Diabetes Mellitus (T2DM) and the regimen used in a recent trial in PD. The treatment period will be 18 months, and patients will be randomly assigned to either active treatment or placebo. Patients with PD diagnosis, stable on medication during the last year, and Hoehn and Yahr stage 2 or less will be evaluated for the inclusion.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
60
Academic Specialist Center, Center for Neurology, SLSO
Stockholm, Sweden
FDG-PET network analysis
Time frame: 21 months
The sum score of MDS-UPDRS part 3 in ON and OFF-medication state
Time frame: 18 and 21 months
MDS-UPDRS part 2
Time frame: 9, 18 and 21 months
MDS-UPDRS part 4
Time frame: 9, 18 and 21 months
Hoehn and Yahr
Time frame: 18 and 21 months
Accelerometer (intensity of physical activity)
Time frame: 18 and 21 months
Accelerometer (steps per day)
Time frame: 18 and 21 months
Accelerometer (time of inactivity per day)
Time frame: 9, 18 and 21 months
Levodopa equivalent daily dose (LEDD)
Time frame: Every 3 months
PDQ-39 mobility subscore
Time frame: 18 months
MDS-UPDRS part 1
Non-motor symptom progression
Time frame: 18 and 21 months
Non-Motor Symptoms Questionnaire (NMSQuest)
Non-motor symptom progression
Time frame: 18 months
PDQ-39 subscores (except for mobility)
Non-motor symptom progression
Time frame: 18 months
Epworth Sleepiness Scale (ESS)
Non-motor symptom progression
Time frame: 18 months
MADRS
Non-motor symptom progression
Time frame: 6, 12 and 18 months
Montreal Cognitive Assessment (MoCA)
Non-motor symptom progression
Time frame: 21 months
Brief Smell Identification Test (B-SIT)
Non-motor symptom progression
Time frame: 18 months
Frequency and severity of Adverse Events
Time frame: 21 months
Exenatide-concentration csf
Time frame: Baseline, 9 and 21 months
Exenatide levels in serum
Time frame: Baseline, 9, 18 and 21 months
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