GRoningen Early-PD Ambroxol Treatment

NCT05830396 | Unknown Phase 2 DMC

• 1 other identifier: 202100266
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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

Keywords

Ambroxol; GBA1; GBA

Outcome Measures

Primary Outcomes (1)

• MDS-UPDRS3 motor scale

  Motor scale developed for PD patients, 0-132. 0 means good performance, 132 means very bad performance

  60 weeks

Secondary Outcomes (7)

• 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

• Glucocerebrosidase (GCase) activity in blood mononuclear cells

  0, 12, 60 weeks

• Striatal F-DOPA uptake as measured by [18] F-DOPA PET scan

  0, 60 weeks

• fMRI resting state to investigate the functional architecture and structural MRI for PET-scan

  0, 60 weeks

• Quality of Life (PDQ-39 questionnaire)

  0, 60 weeks

Study Arms (2)

Ambroxol

EXPERIMENTAL

Ambroxol 1800mg/day

Drug: Ambroxol Hydrochloride

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Ambroxol Hydrochloride 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).

Ambroxol

Placebo 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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Parkinson's disease, according to Movement Disorders Society (MDS) criteria (27)
• 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

You may not qualify if:

• 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:
• 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).
• 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).

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, Netherlands

RECRUITING

Related Publications (1)

• 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.

  PMID: 38693511 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Central Study Contacts

Olav Siemeling

CONTACT

0031 (0)50 3615639; o.siemeling@umcg.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2023
• First Posted: April 26, 2023
• Study Start: May 1, 2023
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: May 10, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)