Overview

Ambroxol as a Disease-modifying Treatment in GBA-PD

Status:
Recruiting

Trial end date:
2024-06-15

Target enrollment:
0

Participant gender:
All

Summary

The present multicenter, randomized, double-blind, placebo-controlled clinical trial will investigate whether the prolonged administration of high-dose oral Ambroxol over 52 weeks is safe, tolerable, able to change Glucocerebrosidase enzyme activity and alpha-synuclein levels in the central nervous system and, ultimately, to reduce the progression of cognitive decline and motor disability in 60 individuals with Parkinson's disease with mutations of the glucocerebrosidase gene (GBA1; OMIM 606463). Participants will undergo clinical, biomarker blood and cerebrospinal fluid analysis, neuropsychological, neuroimaging assessment throughout the course of the study.

Phase:

Phase 2

Accepts Healthy Volunteers?

Details

Lead Sponsor:

Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

Collaborators:

IRCCS National Neurological Institute "C. Mondino" Foundation
University of Campania "Luigi Vanvitelli"

Treatments:

Ambroxol

Criteria

Inclusion Criteria:

1. Age 21-80 years

2. Diagnosis of idiopathic PD

3. Duration of motor symptoms >5 years

4. Heterozygous carrier of a GBA1 mutation.

5. Capable of complying with all study procedures, including fasting lumbar puncture

6. All male and female participants of childbearing age must agree with their partners to
use double barrier birth control or total abstinence during study participation and
for 2 weeks after the last dose of study drug.

Male participants who have received bilateral vasectomy are permanently sterile.

A woman can participate if she is of:

1. Non-childbearing potential

2. Women of childbearing potential must have a negative pregnancy test at the screening
visit and use accepted contraceptive methods defined as highly effective.

Exclusion Criteria:

1. Secondary and primary atypical parkinsonism

2. Diagnosis of Parkinson-Dementia (MDS Level II criteria) or other conditions that
result in inability to understand and sign the informed consent

3. Hoehn & Yahr stage ≥ 4/5 in the medication-ON condition

4. Deep Brain Stimulation

5. Any clinically significant or unstable medical condition, which, in the opinion of the
principal investigator or the clinician delegated by the principal investigator, may
put the participant at risk when participating in the study (e.g. previous
gastric/duodenal peptic ulcer, chronic obstructive pulmonary disease, severe liver or
kidney changes, major cardiovascular event (e.g. myocardial infarction, decompensated
congestive heart failure, pulmonary embolism occurring within 6 months prior to the
screening visit), neoplastic diseases).

6. Bronchial asthma

7. Abnormalities that could preclude safe completion of the spinal cord in the
investigator's opinion, including: treatment with anticoagulants; severe abnormalities
or malformations of the lower spine or other spinal disorders; bleeding diathesis
(e.g. clinically significant coagulopathies or thrombocytopenia); hypersensitivity to
lidocaine.

8. Pregnant or breastfeeding women.

9. All participants of childbearing age who disagree to use double barrier or abstinence
birth control while participating in the study and for 2 weeks after the last dose of
study drug;

10. Known hypersensitivity to the active substance Ambroxol or to any of its excipients.