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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called Ambroxol to determine if it can safely improve thinking and movement problems in people with Parkinson's Disease Dementia (PDD). Ambroxol may help by increasing certain enzymes and reducing a protein linked to brain issues. Participants will receive either Ambroxol or a placebo (a pill with no active medicine) to compare results. The trial seeks individuals who have had Parkinson's for over a year, now have mild to moderate dementia, and are on stable doses of their current medications. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that Ambroxol is likely to be safe for humans?

Research has shown that Ambroxol is generally safe and well-tolerated for people with Parkinson's Disease Dementia (PDD). Studies have found that patients taking Ambroxol did not experience major side effects. It effectively interacts with its target in the body, indicating a positive mechanism of action.

In another study, Ambroxol was safe but did not clearly improve symptoms. While the treatment caused no harm, it also showed no significant improvement. Overall, the evidence suggests that Ambroxol is unlikely to cause harm, though its benefits are still under investigation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Parkinson’s Disease Dementia, such as levodopa and dopamine agonists that primarily address motor symptoms, Ambroxol is unique because it targets the underlying cellular mechanisms. Researchers are excited about Ambroxol because it works by increasing the activity of glucocerebrosidase, an enzyme that helps break down and clear out harmful proteins in brain cells. This could potentially slow down or even halt the progression of dementia symptoms in Parkinson's patients, offering a new hope that extends beyond merely managing symptoms to addressing one of the root causes of the condition.

What evidence suggests that Ambroxol might be an effective treatment for Parkinson's Disease Dementia?

Research has shown that Ambroxol, which participants in this trial may receive, is safe and generally well-tolerated by people with Parkinson's Disease Dementia (PDD). In earlier studies, Ambroxol successfully reached its intended target in the body. However, clear proof is lacking that it helps with thinking or movement problems in PDD. For patients with certain genetic traits, Ambroxol has shown potential in stabilizing thinking and mood symptoms. Overall, while some promising signs exist, it remains uncertain if Ambroxol effectively improves PDD symptoms. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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 do not have any serious health conditions like unstable heart disease or another cancer.

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

I am taking Aspirin, Clopidogrel, or Aggrenox.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40587145/

Ambroxol as a Treatment for Parkinson Disease Dementia Results of this randomized clinical trial reveal that ambroxol was safe, well-tolerated, and demonstrated target engagement.

2. lbda.org lbda.org/trial-results-ambroxol-safe-in-pdd-but-no-clear-evidence-of-benefit/

Trial Results: Ambroxol Safe in PDD, But No Clear ... Trial Results: Ambroxol Safe in PDD, But No Clear Evidence of Benefit - Lewy Body Dementia Association.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02914366

Ambroxol as a Treatment for Parkinson's Disease Dementia In a trial aimed at non-neurological Gaucher disease, 12 patients received 150 mg/day for 6 months, and all but one had some measureable improvement. The best ...

4. practicalneurology.com practicalneurology.com/news/ambroxol-shows-target-engagement-but-no-cognitive-benefit-in-individuals-with-parkinson-disease-dementia/2475884/

Ambroxol Shows Target Engagement but No Cognitive Benefit ... Additionally, participants with GBA1 gene variants treated with ambroxol showed potential cognitive and neuropsychiatric symptom stabilization.

5. healio.com healio.com/news/neurology/20250715/ambroxol-safe-but-efficacy-undetermined-for-symptoms-of-parkinsons-disease-dementia

Ambroxol safe, but efficacy undetermined for symptoms of ... Treatment with ambroxol for symptoms of Parkinson's disease dementia was safe, but its efficacy was undetermined in a small cohort of older ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10679992/

Ambroxol as a disease-modifying treatment to reduce the risk ... Ambroxol as a disease-modifying treatment to reduce the risk of cognitive impairment in GBA-associated Parkinson's disease.

7. frontiersin.org frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1163184/full

The ANeED study – ambroxol in new and early dementia ... The treatment was safe and well tolerated (Mullin et al., 2020). The second study on Parkinson's disease dementia (PDD) randomised, placebo ...