Donepezil for Hearing Loss

Overseen by Aaron Moberly, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Waitlist Available

Sponsor: Vanderbilt University Medical Center

Must be taking: Donepezil

Must not be taking: Anticholinergics, Cholinesterase inhibitors

Disqualifiers: Neurological disorders, Pregnancy, Nicotine, others

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests whether donepezil can help adult cochlear implant users improve their hearing and cognitive functions. Donepezil boosts brain chemicals important for memory and learning, which may help the brain better process sounds from the implant. The study aims to see if this leads to better speech recognition and cognitive outcomes.

Do I need to stop my current medications to join the trial?

You will need to stop taking any medications with known anticholinergic effects (like certain antidepressants and antihistamines) and cholinesterase inhibitors to participate in the trial.

Is donepezil generally safe for humans?

Donepezil, used for Alzheimer's disease, is generally considered safe with common side effects like nausea, diarrhea, dizziness, and insomnia. Serious issues like heart or liver problems are not typically linked to it, but some people may experience unusual dreams or mood changes. ^{1 2 3 4 5}

How does the drug donepezil differ from other treatments for hearing loss?

Donepezil is unique because it is primarily used as a treatment for Alzheimer's disease, where it works by inhibiting an enzyme that breaks down acetylcholine, a chemical important for memory and learning. Its use for hearing loss is novel, as there are no standard treatments for this condition that utilize this mechanism. ^{2 3 6 7 8}

Research Team

René Gifford, PhD

Principal Investigator

Vanderbilt University Medical Center

Mark Wallace, PhD

Principal Investigator

Vanderbilt University

Aaron Moberly, MD

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

Adults over 18 with post-lingual deafness, using a cochlear implant for at least 6 months but less than 11 hours per day. Must be in good health, not pregnant or nursing, non-smokers for the last month, and without major neurological disorders or severe ear abnormalities. Women must use effective contraception and have a negative pregnancy test.

Inclusion Criteria

Your hearing loss started after you learned to speak.

English verbal communication

Your hearing loss is severe enough to be eligible for a cochlear implant according to FDA guidelines.

Exclusion Criteria

I have used or am using medication to improve memory.

Breastfeeding or nursing at any time during the study

You have a positive pregnancy test during the study.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily treatment with either donepezil 5 mg or placebo

3 months

Monthly visits for assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Donepezil (Acetylcholinesterase Inhibitor)
• Placebo (Other)

Trial Overview The trial is testing if Donepezil improves speech recognition and cognitive function in cochlear implant users compared to a placebo. Participants will increase daily device use alongside taking either Donepezil or a placebo pill to see if it enhances hearing outcomes.

Participant Groups

Group I: Experimental Experimental Treatment 1 Intervention

Donepezil 5 mg, daily

Group II: Control Placebo Group 1 Intervention

Placebo, daily

Donepezil is already approved in Canada, Japan for the following indications:

Approved in Canada as Aricept for:

• Alzheimer's disease

Approved in Japan as Aricept for:

• Alzheimer's disease

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Jeffrey R. Balser

Vanderbilt University Medical Center

Chief Executive Officer since 2009

MD and PhD from Vanderbilt University

Rick W. Wright

Vanderbilt University Medical Center

Chief Medical Officer since 2023

MD from University of Missouri-Columbia

Findings from Research

In a pharmacovigilance study of 1762 patients taking donepezil for Alzheimer's disease, common side effects included nausea, diarrhea, malaise, dizziness, and insomnia, but serious issues like cardiac disturbances were not observed.

While the study noted some uncommon adverse reactions such as aggression and abnormal dreams, these findings suggest the need for further research to confirm their association with donepezil.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects associated with the use of donepezil in general practice in England. Dunn, NR., Pearce, GL., Shakir, SA.[2018]

In a 12-week study involving 468 patients with mild to moderately severe Alzheimer disease, donepezil hydrochloride significantly improved cognitive function and clinical outcomes compared to placebo, with notable improvements in ADAS-cog and CIBIC plus scores.

Donepezil was well-tolerated, with a similar incidence of side effects compared to placebo, and did not show the hepatotoxic effects seen with other cholinesterase inhibitors, making it a safe option for treating Alzheimer's symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donepezil improves cognition and global function in Alzheimer disease: a 15-week, double-blind, placebo-controlled study. Donepezil Study Group. Rogers, SL., Doody, RS., Mohs, RC., et al.[2022]

In a 24-week study involving 30 adults with Down syndrome and mild to moderate Alzheimer's disease, donepezil was found to be generally safe and well-tolerated, with no life-threatening side effects reported.

While the results showed some potential efficacy, with 50% of donepezil patients improving in dementia scores compared to 31% on placebo, the small sample size limited the statistical significance of these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Down syndrome and Alzheimer's disease--pilot study. Prasher, VP., Huxley, A., Haque, MS.[2019]

Donepezil is rapidly absorbed after oral administration, with most of the drug remaining unchanged in the brain, indicating that it effectively crosses the blood-brain barrier while its metabolites do not.

The drug is primarily excreted through feces, with extensive metabolism occurring in the body, but no significant accumulation of its metabolites in the brain or other tissues, suggesting a low risk of toxicity from these byproducts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absorption, distribution, metabolism, and excretion of donepezil (Aricept) after a single oral administration to Rat. Matsui, K., Mishima, M., Nagai, Y., et al.[2018]

In a study of 123 patients treated with donepezil for Alzheimer's dementia, 21% discontinued treatment due to adverse events (AEs), highlighting the need for careful monitoring during the initial months of therapy.

The most common AEs leading to discontinuation were nausea/vomiting, diarrhea, and loss of appetite, indicating that these side effects are significant considerations in the management of patients on donepezil.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adverse events causing discontinuation of donepezil for Alzheimer's dementia]. Carøe, TK., Moe, C.[2018]

In a long-term study of 763 patients with mild to moderately severe Alzheimer's disease, donepezil treatment showed sustained cognitive benefits for up to 144 weeks, particularly at a dosage of 10 mg/d.

While donepezil is generally safe with mild and transient side effects, its benefits can diminish after a placebo washout, indicating the importance of continuous treatment for maintaining cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label, multicenter, phase 3 extension study of the safety and efficacy of donepezil in patients with Alzheimer disease. Doody, RS., Geldmacher, DS., Gordon, B., et al.[2022]

A retrospective analysis of 41 elderly Alzheimer's patients from various ethnic backgrounds showed that Donepezil (Aricept) is clinically effective for treating mild to moderate Alzheimer's disease.

The study suggests that Donepezil's efficacy is consistent across different ethnicities, including a significant number of Asian and Hawaiian patients, even in older age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of donepezil in elderly patients with Alzheimer's disease--a Hawaii based study. Alagiakrishnan, K., Wong, W., Blanchette, PL.[2022]

A new class of acetylcholinesterase inhibitors (AChEIs) was developed, specifically an indanone derivative called donepezil hydrochloride (E2020), which showed significant improvements in anti-AChE activity compared to previous inhibitors like physostigmine and tacrine.

Clinical studies of donepezil demonstrated statistically significant cognitive benefits in Alzheimer's patients, as measured by the Alzheimer's Disease Assessment Scale and Clinician's Interview-Based Impression of Change.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Discovery and development of donepezil hydrochloride for the treatment of Alzheimer's disease]. Sugimoto, H., Yamanishi, Y., Ogura, H., et al.[2019]

References

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

Adverse effects associated with the use of donepezil in general practice in England. [2018]

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

Donepezil improves cognition and global function in Alzheimer disease: a 15-week, double-blind, placebo-controlled study. Donepezil Study Group. [2022]

3. England pubmed.ncbi.nlm.nih.gov

A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Down syndrome and Alzheimer's disease--pilot study. [2019]

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

Absorption, distribution, metabolism, and excretion of donepezil (Aricept) after a single oral administration to Rat. [2018]

5. Denmark pubmed.ncbi.nlm.nih.gov

[Adverse events causing discontinuation of donepezil for Alzheimer's dementia]. [2018]

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

Open-label, multicenter, phase 3 extension study of the safety and efficacy of donepezil in patients with Alzheimer disease. [2022]

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

Use of donepezil in elderly patients with Alzheimer's disease--a Hawaii based study. [2022]

8. Japan pubmed.ncbi.nlm.nih.gov

[Discovery and development of donepezil hydrochloride for the treatment of Alzheimer's disease]. [2019]