Ambroxol for Parkinson's Disease Dementia

Overseen By Stephen Pasternak, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Must be taking: Cholinesterase inhibitors

Must not be taking: Oral anticoagulants

Disqualifiers: Stroke, Cancer, Cardiac disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 52 weeks

55 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

You must be on stable doses of medications for Parkinson's disease, mood, and cognition for at least 3 months before the study. However, you cannot take certain blood thinners like Warfarin or Rivaroxaban during the trial, but some like Aspirin are allowed.

How does the drug Ambroxol differ from other treatments for Parkinson's disease dementia?

Ambroxol is unique because it is primarily known as a medication for respiratory conditions, but it is being explored for Parkinson's disease dementia due to its potential to enhance the function of lysosomes (cellular components that break down waste) and improve the clearance of alpha-synuclein, a protein that accumulates in Parkinson's disease. This mechanism is different from other treatments that typically focus on managing symptoms rather than addressing underlying cellular processes. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial tests if Ambroxol, a safe over-the-counter medication, can help people with Parkinson's Disease Dementia by increasing an enzyme that reduces harmful proteins in the brain. The goal is to see if it improves memory and movement problems. Ambroxol has been shown to be safe and well tolerated in previous studies.

Eligibility Criteria

This trial is for individuals over 50 with Parkinson's Disease Dementia (PDD), who have mild to moderate dementia and a caregiver available at least 4 days a week. Participants must be on stable Parkinson's medication for three months, without serious conditions like significant strokes or cancer, and not on oral anticoagulants.

Inclusion Criteria

I have Parkinson's Disease at stage 2 to 3.5, diagnosed over a year before any dementia.

I have been on a steady dose of Parkinson's mood and cognition medication for 3 months.

I am over 50 years old.

Exclusion Criteria

I am not taking any blood thinners like Warfarin or Rivaroxaban.

I am taking Aspirin, Clopidogrel, or Aggrenox.

I have had a stroke or another serious brain condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 or more visits (in-person)

Treatment

Participants receive Ambroxol or placebo with dose escalation every 2 weeks, monitored for cognitive and motor function improvements

52 weeks

Regular visits at weeks 2, 4, 6, 8, 12, 18, 26, 34, 42, and 52

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may opt into continuation of Ambroxol treatment for an additional 6 months

24 weeks

Treatment Details

Interventions

• Ambroxol
• Placebo

Trial Overview The study tests if Ambroxol can improve cognitive and motor symptoms in PDD by increasing beta-glucocerebrosidase levels, potentially lowering alpha-synuclein protein. This year-long trial involves clinical assessments, neuropsychological testing, and neuroimaging to monitor changes.

Participant Groups

Group I: Ambroxol high dose (1050 mg) Experimental Treatment 1 Intervention

Participants randomized to the 1050 mg/day group will begin with a dose of 225mg (3 mg/kg/day), increasing bi-weekly by \~3mg/kg to a dose of 1050 mg/day (\~l5 mg/kg/day).

Group II: Placebo Placebo Group 1 Intervention

Participants receive capsules visually identical to the experimental groups but without active ingredients.

Who Is Running the Clinical Trial?

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Western University, Canada

Collaborator

Trials

270

Recruited

62,500+

London Health Sciences Centre

Collaborator

Trials

151

Recruited

60,400+

University of Western Ontario, Canada

Collaborator

Trials

168

Recruited

320,000+

Weston Brain Institute

Collaborator

Trials

13

Recruited

990+

References

1. United States pubmed.ncbi.nlm.nih.gov

Effects of glutamate and alpha2-noradrenergic receptor antagonists on the development of neurotoxicity produced by chronic rotenone in rats. [2016]

2. England pubmed.ncbi.nlm.nih.gov

Epidemiology of Parkinson's disease. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

The efficacy of a "cocktail therapy" on Parkinson's disease with dementia. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

A review of studies describing the use of acetyl cholinesterase inhibitors in Parkinson's disease dementia. [2007]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Treatment of psychosis in Parkinson's disease: safety considerations. [2022]