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

Trial Summary

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 data supports the effectiveness of the drug Donepezil for dementia?

Research shows that Donepezil, also known as Aricept, helps improve thinking and overall function in people with Alzheimer's disease, a common type of dementia. Studies have found that it can be effective for people with mild to moderate Alzheimer's, improving their cognitive abilities and quality of life. ^{1 2 3 4 5}

Is donepezil generally safe for humans?

Donepezil has been studied for safety in people with Alzheimer's disease, and while it is generally considered safe, some people may experience side effects that can lead to stopping the treatment. ^{1 3 4 6 7}

How is the drug Donepezil unique in treating dementia?

Donepezil is unique because it is a selective acetylcholinesterase inhibitor, which means it helps increase levels of a chemical called acetylcholine in the brain, improving memory and thinking in Alzheimer's patients. It is taken once daily due to its long half-life, and it was the first drug of its kind to be marketed for Alzheimer's in the UK. ^{1 2 3 4 8}

What is the purpose of this trial?

The goal of this clinical trial is to demonstrate potential improvements in clinical trial methods relating to dementia and cognitive decline. The main questions it aims to answer are: * Can an intervention's outcome be better assessed by a latent variable ("δ") integrating cognitive performance with functional status? * Can latent biomarkers of δ guide the selection of an intervention that will modulate dementia severity? * Can a latent variable, derived from information collected remotely from caregivers, preselect subjects most likely to respond to the intervention? * Is the effect of the intervention in fact medicated by changes in the targeted biomarker? In this case, the biomarker will be a latent variable derived from several proteins measured in blood (i.e., so-called "adipokines"). The intervention will be donepezil, a medication approved for the treatment of Alzheimer's Disease, but only recently associated with adipokine changes. Participants with cognitive impairment and their caregivers will be interviewed by telephone and those newly prescribed donepezil by their provider for cognitive impairment will be recruited and enrolled. On the basis of the caregiver's report, the cognitively impaired subjects will be assigned to two groups based on a prediction of their response to donepezil. Researchers will compare those groups to see if dementia severity, as measured by δ, improves in predicted responders, and whether the change in the d-score is mediated by changes in adipokines.

Research Team

Donald R. Royall, MD

Principal Investigator

University of Texas

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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 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 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 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]

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]

References

1. 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]

2. 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]

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

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

5. Austria pubmed.ncbi.nlm.nih.gov

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

6. India 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. [2021]

7. Denmark pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

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