The most common genetic risk factor for Parkinson's Disease is a heterozygous mutation of the GBA1 gene, encoding the lysosomal enzyme glucocerebrosidase (GCase). Reduced GCase activity is associated with aggregation of the protein alpha synucleine (aSyn) in the central nervous system, which is related to the pathological cause of PD. Ambroxol is a mucolytic expectorant that appears to facilitate the refolding of the misfolded GBA protein thats acts as a chaperone for GCase. This randomized placebo-controlled trial aims to investigate the disease-modifying properties of ambroxol in PD patients with a GBA1-mutation. Patients will undergo motor and cognitive tests, as well as imaging and blood tests.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
80
Patients will either receive ambroxol or placebo. ambroxol will be given intially in a dosage of 600mg/day. After 1 week, this will be increased to 1200mg/day. After 2 weeks the maximum dosage of 1800mg/day will be given. In total, ambroxol will be administered for 48 weeks. This is followed by a 12 week washout period, after wich the final outcomes will be measured (week 60).
Patients will either receive ambroxol or placebo. ambroxol will be given intially in a dosage of 600mg/day. After 1 week, this will be increased to 1200mg/day. After 2 weeks the maximum dosage of 1800mg/day will be given. In total, ambroxol will be administered for 48 weeks. This is followed by a 12 week washout period, after wich the final outcomes will be measured (week 60).
University Medical Center Groningen
Groningen, Netherlands
RECRUITINGMDS-UPDRS3 motor scale
Motor scale developed for PD patients, 0-132. 0 means good performance, 132 means very bad performance
Time frame: 60 weeks
Safety and tolerability measured by incidence of adverse events and possible side effects
AE will be monitored and patients will be questioned about side effects every week during the first 3 weeks and after that, every 3 months during the visits
Time frame: all throughout the study. specifically at: 1, 2, 3, 12, 24, 36, 48, 60 weeks
Glucocerebrosidase (GCase) activity in blood mononuclear cells
Measured by the level of sphingolipids in PBMCs
Time frame: 0, 12, 60 weeks
Striatal F-DOPA uptake as measured by [18] F-DOPA PET scan
Time frame: 0, 60 weeks
fMRI resting state to investigate the functional architecture and structural MRI for PET-scan
Fluctuations in the BOLD signal can be used to investigate the functional architecture and connectivity within the brain.
Time frame: 0, 60 weeks
Quality of Life (PDQ-39 questionnaire)
Time frame: 0, 60 weeks
Non Motor Symptoms (NMSS scale)
minimum value is 0, maximum value is 360. 0 indicating a good performance, 360 indicating a very bad performance
Time frame: 0, 60 weeks
Cognition, using the Montreal Cognitive Assessment (MoCA)
Range is 0-30, 0 indicating the worst performance, 30 indicating the best performance
Time frame: 0, 60 weeks
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