GRoningen Early-PD Ambroxol Treatment

NCT ID: NCT05830396

Last Updated: 2023-05-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-31
• Study Completion Date: 2025-07-31

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.

Conditions

Parkinson; Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ambroxol

Ambroxol 1800mg/day

Group Type: EXPERIMENTAL

Ambroxol Hydrochloride

Intervention Type: DRUG

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

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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).

Interventions

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).

Intervention Type: DRUG

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).

Intervention Type: DRUG

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University Medical Center Groningen

Groningen, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Olav Siemeling

Role: CONTACT

o.siemeling@umcg.nl

0031 (0)50 3615639

Facility Contacts

Olav Siemeling

Role: primary

o.siemeling@umcg.nl

0031 (0)50 3615639

References

Siemeling O, Slingerland S, van der Zee S, van Laar T. Study protocol of the GRoningen early-PD Ambroxol treatment (GREAT) trial: a randomized, double-blind, placebo-controlled, single center trial with ambroxol in Parkinson patients with a GBA mutation. BMC Neurol. 2024 May 1;24(1):146. doi: 10.1186/s12883-024-03629-9.

Reference Type: DERIVED

PMID: 38693511 (View on PubMed)

Other Identifiers

202100266

Identifier Type: -

Identifier Source: org_study_id