Ambroxol treatment for Parkinson's patients with a GBA1 mutation

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

This study is testing whether ambroxol can help improve symptoms in people with Parkinson's disease who have a GBA1 mutation.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Medical Center Groningen (Academic / other)
• Locations: 1 site (Groningen)
• Trial ID: NCT05830396 on ClinicalTrials.gov

What this trial studies

This interventional trial investigates the effects of ambroxol, a mucolytic expectorant, on patients with Parkinson's disease who carry a GBA1 mutation. The study aims to determine whether ambroxol can modify the disease by improving the activity of the GCase enzyme, which is crucial for preventing the aggregation of alpha synuclein in the brain. Participants will be randomly assigned to receive either ambroxol or a placebo, and their motor and cognitive functions will be assessed through various tests, including imaging and blood tests. The trial is designed to provide insights into the potential therapeutic benefits of ambroxol in this specific patient population.

Who should consider this trial

Good fit: Ideal candidates are individuals diagnosed with Parkinson's disease for 10 years or less who carry a GBA1 mutation.

Not a fit: Patients with severe dysphagia or those who have undergone deep brain stimulation may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could slow the progression of Parkinson's disease in patients with a GBA1 mutation.

How similar studies have performed: While this approach is novel in the context of ambroxol for Parkinson's disease, similar studies targeting GBA1 mutations have shown promise in other contexts.

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).

Where this trial is running

Groningen

• University Medical Center Groningen — Groningen, Netherlands (Recruiting)

Study contacts

• Study coordinator: Olav Siemeling

Conditions Parkinson; Parkinson Disease; Ambroxol; GBA1; GBA