Donepezil for Anorexia

Overseen By Joanna Steinglass, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: New York State Psychiatric Institute

Must not be taking: Antipsychotics

Disqualifiers: Schizophrenia, Bipolar, Substance use, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of donepezil for people with anorexia nervosa. Typically used for Alzheimer's, donepezil might help reduce harmful eating habits. Participants will gradually increase their dose to 5 mg per day over eight weeks, with close monitoring for any side effects. The study is open to individuals diagnosed with anorexia nervosa who are receiving treatment at the New York State Psychiatric Institute Eating Disorders Unit and meet specific health criteria. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does allow antidepressants if they are at a stable dose. Antipsychotic medications are not allowed.

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

Research has shown that donepezil, the treatment being tested, is generally well-tolerated. Patients have used it for over 770 million days, indicating a strong safety record. Studies have identified common side effects, including nausea, diarrhea, trouble sleeping, vomiting, muscle cramps, tiredness, and loss of appetite.

Donepezil has already received approval for other conditions, meaning the FDA has reviewed its safety. This approval provides some confidence about its safety, although its specific effects on anorexia nervosa patients remain under study.

Researchers will closely monitor participants in this study to quickly address any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for anorexia?

Most treatments for anorexia focus on nutritional rehabilitation and psychotherapy to help patients regain weight and address psychological factors. However, Donepezil is unique because it targets the brain's neurotransmitter system, specifically enhancing acetylcholine activity, which might improve cognitive function and appetite regulation. Researchers are excited about Donepezil because it offers a novel approach by potentially addressing the neurological aspects of anorexia, which could complement traditional therapies and provide a more holistic treatment strategy.

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

Research has shown that donepezil, a drug typically used for Alzheimer's disease, might also benefit people with anorexia nervosa. This medication boosts certain brain chemicals that improve memory and mood. Early results suggest that donepezil may enhance well-being in those with anorexia by potentially altering harmful eating patterns. While it helps with thinking skills in dementia, its effects on anorexia are still under investigation in this trial. More research is needed to confirm its effectiveness specifically for anorexia. ^{2 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with anorexia nervosa receiving care at the New York State Psychiatric Institute Eating Disorders Unit. Participants will be given donepezil, starting at 1 mg per day and potentially increasing to 5 mg daily over 8 weeks.

Inclusion Criteria

Provision of signed and dated informed consent form

I am willing and able to follow all study requirements.

BMI ≥ 15 kg/m2 (Clinical team medical record)

Exclusion Criteria

I have a history of irregular heartbeats.

Current diagnosis of schizophrenia, schizophreniform disorder, bipolar (type I), or substance use disorder (SCID)

Bradycardia (below 60 bpm) (vital signs measurement by the clinical team)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive donepezil with flexible titration from 1 mg to 5 mg over 8 weeks

8 weeks

Weekly visits with a research psychiatrist

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 study aims to test the feasibility and tolerability of donepezil in patients with anorexia nervosa. The medication dosage may increase gradually, and changes in maladaptive eating habits will be monitored throughout the treatment.

How Is the Trial Designed?

Group I: Open Label Experimental Treatment 1 Intervention

Donepezil

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?

New York State Psychiatric Institute

Lead Sponsor

Trials

481

Recruited

154,000+

Published Research Related to This Trial

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]

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 160 patients with moderate to severe Alzheimer's disease, those with lower body weight were more likely to experience adverse events (AEs) when treated with high-dose donepezil (23 mg), indicating a safety concern for this population.

The analysis suggests that using a stepwise dose titration approach, especially for patients with low body weight, may help reduce the risk of AEs associated with donepezil treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Body Weight on the Safety of High-Dose Donepezil in Alzheimer's Disease: Post hoc Analysis of a Multicenter, Randomized, Open-Label, Parallel Design, Three-Arm Clinical Trial. Hong, YJ., Han, HJ., Youn, YC., et al.[2021]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06687993?term=acetylcholinesterase&viewType=Table&rank=7

Acetylcholinesterase Inhibitor in Anorexia Nervosa ... The goal of this clinical trial is to learn if the daily take of donepezil can treat adult patient suffering from anorexia nervosa.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/19388874/

Donepezil (aricept) as a treatment for anorexia nervosa Donepezil is a drug that been proven to be effective in the treatment of dementia, including Alzheimer's; it has been used for affective disorders.

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

Aricept (donepezil hydrochloride) Label - accessdata.fda.gov ARICEPT has been shown to be effective in controlled clinical trials at doses of 10 mg and 23 mg administered once daily. Results of a controlled clinical trial ...

4. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effects-of-donepezil-in-patients-with-anorexia-nervosa/

Study on the Effects of Donepezil in Patients with Anorexia ... In this study, researchers are testing whether donepezil can help people with anorexia nervosa feel better compared to those who do not receive the medication.

5. 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 ...

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

The safety and tolerability of donepezil in patients with ... Over 770 million days of patient use and an extensive publication database demonstrate that donepezil has a good tolerability and safety profile.

7. alzres.biomedcentral.com alzres.biomedcentral.com/articles/10.1186/s13195-019-0492-1

Safety and tolerability of donepezil 23 mg with or without ... Our study showed three major findings. · Second, cholinergic side effects including anorexia, dizziness, nausea, vomiting, generalized weakness, ...