GRoningen Early-PD Ambroxol Treatment

Parkinson Disease Clinical Trial

— GREAT  

Official title:

GRoningen Early-PD Ambroxol Treatment (GREAT) Trial: A Randomised, Double-blind, Placebo-controlled, Singlecenter Trial With Ambroxol in Parkinson Patients With a GBA Mutation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05830396
• Other study ID #: 202100266
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: May 2023
• Est. completion date: July 2025

Study information

• Verified date: May 2023
• Source: University Medical Center Groningen
• Contact: Olav Siemeling
• Phone: 0031 (0)50 3615639
• Email: o.siemeling[@]umcg.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: July 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Parkinson
• Parkinson Disease

Intervention

Drug:
• Ambroxol Hydrochloride
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).
• Placebo
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).

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MDS-UPDRS3 motor scale	Motor scale developed for PD patients, 0-132. 0 means good performance, 132 means very bad performance	60 weeks
Secondary	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	all throughout the study. specifically at: 1, 2, 3, 12, 24, 36, 48, 60 weeks
Secondary	Glucocerebrosidase (GCase) activity in blood mononuclear cells	Measured by the level of sphingolipids in PBMCs	0, 12, 60 weeks
Secondary	Striatal F-DOPA uptake as measured by [18] F-DOPA PET scan		0, 60 weeks
Secondary	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.	0, 60 weeks
Secondary	Quality of Life (PDQ-39 questionnaire)		0, 60 weeks
Secondary	Non Motor Symptoms (NMSS scale)	minimum value is 0, maximum value is 360. 0 indicating a good performance, 360 indicating a very bad performance	0, 60 weeks
Secondary	Cognition, using the Montreal Cognitive Assessment (MoCA)	Range is 0-30, 0 indicating the worst performance, 30 indicating the best performance	0, 60 weeks