GRoningen Early-PD Ambroxol Treatment

Phase 2

Recruiting

• Conditions: Parkinson; Parkinson Disease
• Interventions: Drug: Ambroxol Hydrochloride; Drug: Placebo

• Registration Number: NCT05830396
• Lead Sponsor: University Medical Center Groningen

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-03-20
• Study First Submitted QC: 2023-04-13
• Study First Posted: 2023-04-26
• Status Verified: 2023-05
• Study Start: 2023-05
• Last Update Submitted: 2023-05-08
• Last Update Posted: 2023-05-10
• Primary Completion: 2025-07
• Study Completion: 2025-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• Diagnosis of Parkinson's disease, according to Movement Disorders Society (MDS) criteria (27)
• Disease duration of 10 years or less at time of inclusion
• PD patients carrying a GBA1 mutation
• Able to write written informed consent, understanding study protocol and perform protocol related actions
• Willing and able to self-administer oral ambroxol or placebo medication

Exclusion Criteria

• The refusal to be informed about an unforeseen clinical finding

• Use of an implanted Deep Brain Stimulation (DBS) system

• Confirmed dysphagia that would preclude self-administration of ambroxol or placebo tablets

• History of known sensitivity to the study medication

• Pregnant or breastfeeding women

• Participants of childbearing potential that would not use adequate birth control, consisting of a negative pregnancy test at the screening visit and use of accepted contraceptive methods defined as highly effective while participating in the study

• MRI incompatible implants in the body

• Any clinically significant or unstable medical or surgical condition that in the opinion of the principal investigator may put the participant at risk when participating in the study or may influence the results of the study or affect the participant's ability to take part in the study, as determined by medical history, physical examinations, electrocardiogram (ECG), or laboratory tests. Such conditions may include:

  1. Impaired renal function (a positive urine dipstick test, and laboratory values below or above: a eGFR <45 ml/min 1,73M2, Sodium 135-145 mmol/L, Potassium 3.5-5.0 mmol/L, Urea 2.5-7.5mmol/L).
  2. Moderate/severe hepatic impairment (laboratory values below or above: ASAT 0- 80U/L, ALAT0-90 U/L, GGT > 80 U/L, Alkaline Phosphatase 35-210 U/L).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ambroxol	Ambroxol Hydrochloride	Ambroxol 1800mg/day
Placebo	Placebo	Placebo

Primary Outcome Measures

Name	Time	Method
MDS-UPDRS3 motor scale	60 weeks	Motor scale developed for PD patients, 0-132. 0 means good performance, 132 means very bad performance

Secondary Outcome Measures

Name	Time	Method
Safety and tolerability measured by incidence of adverse events and possible side effects	all throughout the study. specifically at: 1, 2, 3, 12, 24, 36, 48, 60 weeks	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
Glucocerebrosidase (GCase) activity in blood mononuclear cells	0, 12, 60 weeks	Measured by the level of sphingolipids in PBMCs
Striatal F-DOPA uptake as measured by [18] F-DOPA PET scan	0, 60 weeks
Cognition, using the Montreal Cognitive Assessment (MoCA)	0, 60 weeks	Range is 0-30, 0 indicating the worst performance, 30 indicating the best performance
fMRI resting state to investigate the functional architecture and structural MRI for PET-scan	0, 60 weeks	Fluctuations in the BOLD signal can be used to investigate the functional architecture and connectivity within the brain.
Quality of Life (PDQ-39 questionnaire)	0, 60 weeks
Non Motor Symptoms (NMSS scale)	0, 60 weeks	minimum value is 0, maximum value is 360. 0 indicating a good performance, 360 indicating a very bad performance

Trial Locations

Locations (1)

University Medical Center Groningen; 🇳🇱 Groningen, Netherlands