Donepezil for Dementia

(δND Trial)

Overseen By Floyd Jones

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: The University of Texas Health Science Center at San Antonio

Must be taking: Donepezil

Must not be taking: Opiates, Muscle relaxants, Steroids

Disqualifiers: Psychosis, Parkinson's, Cancer, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 24 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve the conduct of clinical trials for dementia treatments, focusing on donepezil, a medication used for Alzheimer's. The researchers explore whether a new method can better assess cognitive and functional changes and if specific blood markers, called adipokines, can predict who will benefit most from the treatment. Participants with memory problems who have recently been prescribed donepezil and have a caregiver to report on their condition might be a good fit. The trial will compare groups predicted to respond well to donepezil with those not expected to see as much benefit, based on caregiver input. As an unphased trial, this study offers participants the chance to contribute to innovative research that could enhance future dementia treatments.

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 cannot participate if you are currently taking donepezil or any other similar medications, or if you are on opiates, muscle relaxants, or systemic steroids.

What prior data suggests that this method is safe for assessing dementia interventions?

Research has shown that donepezil is generally well-tolerated by people with dementia. Studies have found that common side effects include nausea and vomiting, but these occur less frequently with donepezil compared to some other dementia treatments. Specifically, only 11% of patients reported nausea, and 7% reported vomiting.

The FDA has approved donepezil for treating Alzheimer's disease, a type of dementia, indicating its safety for this use. Over time, many patients taking donepezil experience stable or improved dementia symptoms.

Overall, donepezil has a strong safety record, with most people experiencing only mild side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it uses a predictive algorithm to tailor donepezil treatment for dementia patients. This algorithm analyzes caregiver reports to predict who is most likely to respond to donepezil, potentially optimizing patient outcomes. Unlike traditional one-size-fits-all approaches, this personalized method aims to ensure patients receive the treatment most likely to benefit them, which could enhance cognitive performance and overall quality of life.

What is the effectiveness track record for donepezil in treating dementia?

Research has shown that donepezil improves memory and thinking in people with Alzheimer's disease. Studies have found that both 5 mg and 10 mg doses of donepezil enhance cognitive abilities in those with dementia. A review of several studies found that donepezil, especially when combined with another drug called memantine, significantly benefits people with severe memory problems. Additionally, donepezil is considered safe and effective for people with dementia living in care facilities. These findings support using donepezil to manage symptoms of memory decline. In this trial, a response predictor algorithm will assign participants to groups, with donepezil administered as part of their standard care. ^{1 6 7 8 9}

Who Is on the Research Team?

Donald R. Royall, MD

Principal Investigator

University of Texas

Are You a Good Fit for This Trial?

This trial is for people aged 65-100 with Alzheimer's Disease (AD) or Mild Cognitive Impairment (MCI), who can walk, have someone to report on their condition, and can consent to the study. They shouldn't be severely depressed or have major hearing/visual issues. Those already on certain dementia drugs, with recent major surgery, depression diagnosis, heart rhythm problems, cancer treatment within 5 years (except skin cancer), psychosis history, Parkinson's disease or related disorders are excluded.

Inclusion Criteria

My cognitive function score is between 0.0 and -1.0, compared to a standard group.

I can move around on my own and have someone who knows my health condition well.

I understand the details of the clinical trial and can consent to participate.

Exclusion Criteria

I have or have been treated for Parkinson's, tremor, or REM behavior disorder.

I have been treated for or have a history of atrial fibrillation.

I have had psychosis or seen things that weren't there.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (telephone)

Treatment

Participants receive donepezil, with effects on dementia severity measured by δ and adipokines

24 weeks

Baseline, weeks 4, 12, and 24 (telephone)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Donepezil

Trial Overview The trial tests if donepezil affects a new measure called 'δ' that combines cognitive performance and functional status in dementia patients. It also looks at whether changes in blood proteins ('adipokines') relate to how well donepezil works. Participants will take donepezil for six months while researchers track δ scores and adipokine levels.

How Is the Trial Designed?

Group I: Predicted Responders Experimental Treatment 1 Intervention

Group assignment determined by a response predictor algorithm derived from remotely acquired caregiver reports of cognitive performance. The donepezil administered during the study is prescribed by the subject provider as standard of care.

Group II: Predicted Non-Responders Experimental Treatment 1 Intervention

Group assignment determined by a response predictor algorithm derived from remotely acquired caregiver reports of cognitive performance. The donepezil administered during the study is prescribed by the subject provider as standard of care.

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?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

Donepezil is a specific and reversible inhibitor of acetylcholinesterase, which increases acetylcholine levels in the brain, and has been shown to significantly improve cognitive function in patients with mild to moderate Alzheimer's disease after 12 to 24 weeks of treatment.

The most common side effects of donepezil are gastrointestinal issues like nausea and diarrhea, but it has a favorable safety profile with no evidence of liver toxicity, making it a viable long-term treatment option for Alzheimer's.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacology of donepezil: a new treatment of Alzheimer's disease. Wilkinson, DG.[2019]

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 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 12-week study involving 182 patients with mild to moderate Alzheimer's disease, donepezil hydrochloride significantly improved cognitive function, as measured by the Mini Mental Status Examination (MMSE), with scores rising from 16.72 to 19.77 (P<0.0001).

The therapy was well tolerated, with over 80% of caregivers and more than 90% of clinicians rating its efficacy as very good to good, and adverse events were consistent with known safety profiles of donepezil.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of donepezil hydrochloride in patients with mild to moderate Alzheimer's disease: Findings of an observational study. Mehta, S., Chandersekhar, K., Prasadrao, G., et al.[2021]

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]

A 30-week double-blind study in the US showed that Donepezil (5 or 10 mg) significantly improved cognitive and clinical assessments compared to placebo, indicating its efficacy in treating cognitive decline.

The use of Donepezil in the UK emphasizes the importance of addressing non-cognitive behaviors, which can greatly enhance quality of life, alongside cognitive improvements, without significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with Donepezil (Aricept) in the UK. Wilkinson, D.[2019]

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]

Citations

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

Donepezil for dementia due to Alzheimer's disease - PMC Two studies compared donepezil 10 mg/day to donepezil 23 mg/day. There were no differences on efficacy outcomes, but fewer participants on 10 mg/day experienced ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11298496/

Efficacy of 5 and 10 mg donepezil in improving cognitive ... Both donepezil 5 mg/day and 10 mg/day doses demonstrated improved cognitive functions for patients with dementia, however results indicated that the 10 mg/day ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S266724212500082X

A meta-analysis update evaluating the treatment effects of ... This meta-analysis suggests that combination therapy with donepezil and memantine significantly benefits patients with severe cognitive impairment.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00571064

The Effectiveness And Safety Of Donepezil Hydrochloride ... This is a study to determine the effectiveness and safety of donepezil hydrochloride (E2020) used to treat residents of assisted living facilities diagnosed ...

5. bmcneurol.biomedcentral.com bmcneurol.biomedcentral.com/articles/10.1186/1471-2377-14-83

Donepezil and life expectancy in Alzheimer's disease The similar life expectancies in patients taking donepezil at home and those not taking donepezil in a nursing home indicated a positive health ...

6. frontiersin.org frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1398952/full

Efficacy of 5 and 10 mg donepezil in improving cognitive ... Both donepezil 5 mg/day and 10 mg/day doses demonstrated improved cognitive functions for patients with dementia, however results indicated that the 10 mg/day ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1884556/

The safety and tolerability of donepezil in patients with ... Nausea and vomiting were reported in 42% and 24% of rivastigmine-treated vs. 11% and 7% of donepezil-treated patients, respectively [29]. These results are ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00165763

Efficacy and Safety of Donepezil Hydrochloride (Aricept) in ... The purpose of this study is to examine the efficacy and safety of cholinesterase inhibitor (donepezil hydrochloride) Aricept in patients with vascular dementia ...

9. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/psyg.12340

Disease state changes and safety of long‐term donepezil ... The percentages of patients whose dementia severity improved or remained the same compared with baseline were 59.27% at 48 months in the newly ...