Donepezil for Parkinson's Disease

Overseen By Hannah Caballero, MSW

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Virginia

Must be taking: Levodopa, Anti-parkinsonian

Must not be taking: Donepezil, Rivastigmine

Disqualifiers: Deep brain stimulator, Cognitive impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

5 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the medication Donepezil can improve walking and balance issues in people with Parkinson's disease. These issues often complicate daily life, causing challenges like shuffling feet or feeling stuck to the floor. The study aims to determine if Donepezil can increase levels of the brain chemical acetylcholine, potentially aiding these movement problems. It suits those diagnosed with Parkinson's who have trouble walking but can still walk unassisted. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be on a stable dose of levodopa or other anti-parkinsonian medications. You cannot currently use donepezil, rivastigmine, galantamine, or memantine.

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

Research has shown that donepezil is generally safe and well-tolerated for people with Parkinson's disease. One study found that symptoms of Parkinson's did not worsen while taking donepezil, reassuring those concerned about this issue. Another study found that donepezil helped with cognitive problems and improved other non-motor symptoms, indicating broad safety.

A different study examined patients with Parkinson's-related dementia and found donepezil to be safe and effective. Long-term use of donepezil at 5 mg daily was also well-tolerated in patients with a similar condition, suggesting safety in this context as well.

Overall, these findings suggest that donepezil is generally safe for people with Parkinson's, especially under healthcare professional supervision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Parkinson’s disease, which typically focus on managing symptoms like tremors and stiffness, Donepezil is being explored for its potential to improve gait dysfunction. Donepezil, known primarily for treating Alzheimer's symptoms, works by enhancing communication between nerve cells in the brain. Researchers are excited because this approach targets cognitive aspects that might translate into improved movement, offering a dual benefit for patients with Parkinson's. This could provide a unique advantage, as it addresses both mental and physical symptoms in a condition where both are deeply intertwined.

What evidence suggests that Donepezil might be an effective treatment for Parkinson's disease?

Studies have shown that donepezil, a medication that increases acetylcholine in the brain, can improve thinking and behavior in people with Parkinson's disease. Research suggests that while donepezil is often used for memory problems in Parkinson's patients, it might also help with movement issues like walking and balance. These movement problems relate to lower acetylcholine levels, so increasing this chemical could be beneficial. Although most research focuses on memory and thinking benefits, the potential to improve movement is promising because it targets the same chemical pathway. Participants in this trial will receive donepezil to explore its potential benefits on movement issues in Parkinson's disease. ^{1 2 3 5 6}

Who Is on the Research Team?

William A Dalrymple, MD

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

This trial is for individuals with Parkinson's Disease who have difficulties with walking and balance. The study aims to understand if a medication, ARICEPT (Donepezil hydrochloride), can help improve these issues.

Inclusion Criteria

I can walk without help from devices like canes or walkers.

Subject agrees not to participate in another study with an investigational drug/treatment during this study and for 3 months following study completion

I am not breastfeeding, have a negative pregnancy test, and if able to bear children, I use birth control.

Exclusion Criteria

Presence of specific medical conditions that could affect the outcome of the study

Score of 3 or higher on the Anticholinergic Cognitive Burden Scale

I am currently taking medication for memory problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

MRIs will be obtained for Ch4 GMD quantification and gait metrics will be measured

1 week

1 visit (in-person)

Treatment

Participants receive donepezil (5mg nightly for 4 weeks, then 10mg nightly for 8 weeks)

12 weeks

1 visit (in-person) at week 12, 1 telephone check-in at week 6

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Donepezil

Trial Overview The trial is testing whether Donepezil, a drug that increases levels of acetylcholine in the brain, can improve gait and balance in people with Parkinson's by affecting an area of the brain called Cholinergic Nucleus 4.

How Is the Trial Designed?

Group I: Donepezil Experimental Treatment 1 Intervention

Patients with Parkinson's disease and gait dysfunction will be enrolled. We will measure gait metrics and obtain an MRI at baseline, then everyone will begin donepezil (5mg nightly for 4 weeks, followed by 10mg nightly). There will be a telephone check in at week 6, then at week 12 they will return for repeat gait metrics

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1737925/

Donepezil for cognitive impairment in Parkinson's disease Results: Two patients on donepezil (14%) dropped out after one and four weeks of the first treatment period because of peripheral cholinergic side effects, ...

2. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00301-7/fulltext

Effect of donepezil for dementia prevention in Parkinson's ... A 4-year administration of donepezil did not change the incidence of dementia in PD patients with severe olfactory dysfunction. On the other ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/16163744/

A Comparison of the Efficacy of Donepezil in Parkinson's ... Conclusions: Donepezil produced similar improvements in cognition and behaviour in DLB and PDD.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01327859?cond=%22Parkinson's%20Disease%22&intr=%22Donepezil%22&viewType=Table&rank=1

Safety, Tolerability, and Efficacy of Donepezil (Aricept) in ... The purpose of this study is to evaluate the safety, tolerability, and efficacy of donepezil (Aricept) in Parkinson's Disease (PD) patients with dementia.

5. nature.com nature.com/articles/s41598-021-84243-4

Donepezil for mild cognitive impairment in Parkinson's ... The treatment group received donepezil for 48 weeks. The primary outcome measures were the Korean version of Mini-Mental State Exam and Montreal ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23949147/

Long-term safety and efficacy of donepezil in patients with ... Conclusion: The long-term administration of donepezil at 5 mg/day was well tolerated in patients with DLB and is expected to exhibit lasting effects, improving ...