Donepezil for Hearing Loss

Overseen By Ansley Kunnath, BA

Age: 18+

Sex: Any

Trial Phase: Phase < 1

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 This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether donepezil, a medication typically used for memory issues, can enhance hearing and cognitive skills in individuals with cochlear implants. The researchers aim to determine if donepezil can help the brain better adapt to sounds from the implant, potentially improving speech understanding and mental functions. Participants will take either donepezil or a placebo (a pill without active medicine) daily for up to three months. Suitable candidates are adults who have used a cochlear implant for at least six months and developed hearing loss after learning to speak. As an Early Phase 1 trial, this research focuses on understanding how donepezil affects people with cochlear implants, offering a unique opportunity to contribute to groundbreaking research.

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

Research has shown that donepezil is generally safe for people. This medication, used to alleviate Alzheimer's disease symptoms, typically does not cause serious side effects. Common side effects include nausea, diarrhea, and trouble sleeping, but these are often mild.

The FDA has already approved donepezil for Alzheimer's, indicating its safety for that use. Serious side effects are rare, though some individuals have reported confusion, sweating, and a slow heart rate. Anyone considering joining the trial should discuss any concerns with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for hearing loss involve hearing aids or cochlear implants to amplify or bypass the damaged parts of the ear. But Donepezil, a drug commonly used to treat Alzheimer's disease, is being explored for hearing loss due to its potential to enhance brain function. Unlike traditional options, Donepezil works by boosting the levels of a neurotransmitter called acetylcholine, which might improve auditory processing in the brain. Researchers are excited about Donepezil because it targets the cognitive aspects of hearing, potentially offering a novel approach to managing hearing loss beyond just amplifying sound.

What evidence suggests that donepezil might be an effective treatment for hearing loss?

Research has shown that donepezil, which participants in this trial may receive, might improve hearing and thinking skills in people with cochlear implants. Donepezil increases certain brain chemicals that aid memory and learning. Early findings suggest that donepezil can help the brain better understand sounds. Some studies indicate that donepezil may enhance speech recognition by helping the brain adjust to new hearing experiences. Although more research is needed, initial results are promising for donepezil's potential in aiding hearing improvement. ^{2 6 7 8 9}

Who Is on the 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

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Donepezil
• Placebo

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.

How Is the Trial Designed?

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 European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Aricept for:

• Alzheimer's disease

Approved in United States as Aricept for:

• Alzheimer's disease
• Mild to moderate dementia of the Alzheimer's type

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

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]

Citations

1. withpower.com withpower.com/trial/early-phase-1-hearing-loss-8-2022-979af

Donepezil for Hearing Loss · Info for Participants This trial tests whether donepezil can help adult cochlear implant users improve their hearing and cognitive functions. Donepezil boosts brain chemicals ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00754013?term=donepezil&viewType=Table&rank=7

Evaluating The Efficacy And Safety Of Donepezil ... The purpose of this study is to determine the efficacy and safety of donepezil hydrochloride ( Aricept ) in the treatment of cognitive dysfunction shown by ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4487900/

Normal Hearing Ability but Impaired Auditory Selective ... Donepezil responders (MMSE 3+) also showed improvement on the ASA test. At baseline, the responders had higher vigilance and lower ASA test scores. Conclusion.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12552022/

Hearing All About Donepezil: Its Role in the Field of Auditory ... Her significant history of hearing loss with auditory hallucination impressively responded to the initiation of donepezil. There may be ...

5. trialx.com trialx.com/clinical-trials/listings/269228/effect-of-donepezil-on-speech-recognition-in-cochlear-implant-users/

Effect of Donepezil on Speech Recognition in Cochlear ... The findings from this study will provide important insight into the mechanisms of hearing restoration and could potentially improve hearing and cognitive ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6513124/

Donepezil for dementia due to Alzheimer's disease - PMC To assess the clinical efficacy and safety of donepezil in people with mild, moderate or severe dementia due to Alzheimer's disease.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2012/020690s035,021720s008,022568s005lbl.pdf

Aricept (donepezil hydrochloride) Label - accessdata.fda.gov The efficacy and safety data presented in the clinical trials section were obtained from these patients. There were no clinically significant differences in ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7752397/

Suspected donepezil toxicity: A case report - PMC Donepezil toxicity can present similarly to beta‐blocker overdose and colitis. Symptoms include confusion, diaphoresis, and bradycardia.

9. mayoclinic.org mayoclinic.org/drugs-supplements/donepezil-oral-route/description/drg-20063538

Donepezil (oral route) - Side effects & dosage Donepezil is used to treat dementia (memory loss and mental changes) ... Safety and efficacy have not been established. Geriatric.