An Open Trial of a Novel Pharmacotherapy for Habit Modification in Anorexia Nervosa

NCT06518941 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: NKI2024-90
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the feasibility and tolerability of donepezil in a small group of patients with anorexia nervosa (AN). Study participants will be receiving care at the New York State Psychiatric Institute Eating Disorders Unit. Study medication will be increased from 1 mg per day to a maximum of 5 mg per day for up to 8 weeks. Participants will be closely monitored for side effects by a research psychiatrist every week, in addition to the regular clinical monitoring they receive during inpatient treatment. The study will also include assessments of habit strength to measure any changes in maladaptive eating habits over the course of the treatment.

Conditions

Anorexia Nervosa

Keywords

anorexia; anorexia nervosa; donepezil; eating disorders; acetylcholinesterase inhibitor; Acetylcholine; habit

Outcome Measures

Primary Outcomes (2)

• Side Effects Form

  The study psychiatrist will assess the tolerability of donepezil during weekly meetings with participants. The presence of side effects will be assessed using the Side Effects Form. Higher scores indicate more severe side effects (each side effect is scored separately). The Clinical Global Impressions (CGI) scale will evaluate overall functioning and psychopathology.

  From enrollment to the end of treatment at 8 weeks

• Clinical Global Impressions Scale

  The Clinical Global Impressions Scale (CGI) is a seven-point scale. A score of 1 indicates the most positive change in the treatment course and the least severity of psychopathology, while a score of 7 indicates the most negative change in the treatment course and the highest severity of psychopathology.

  From enrollment to the end of treatment at 8 weeks

Secondary Outcomes (2)

• Self-Report Habit Index

  From enrollment to the end of treatment at 8 weeks

• Food Choice Task

  From enrollment to the end of treatment at 8 weeks

Study Arms (1)

Open Label

EXPERIMENTAL

Donepezil

Drug: Donepezil

Interventions

Donepezil DRUG

Study medication will be initiated at 1mg, to be taken before bed. Dosing will follow a flexible titration. The expected titration will be 1 mg for 2 weeks, 2.5 mg for 2 weeks, then 5 mg for 4 weeks. Doses may be lowered from those recommended by the protocol if side effects are significant.

Open Label

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study (Clinical interview).
• Aged 18-60 years (Clinical interview).
• Diagnosed with anorexia nervosa (EDA-5).
• BMI ≥ 15 kg/m2 (Clinical team medical record)

You may not qualify if:

• Score of High Risk on the Columbia Suicide Severity Scale (C-SSRS).
• Pregnancy (Serum pregnancy test on admission).
• 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)
• Corrected QT interval (QTc) greater than 480 ms at baseline (EKG).
• Antipsychotic medication (antidepressants at a stable dose are allowed) (clinical interview).
• Known allergic reactions to components of the donepezil (e.g., known hypersensitivity to donepezil hydrochloride) (clinical interview).
• History of peptic ulcer disease (clinical interview).
• History of arrhythmia (clinical interview).

Sponsors & Collaborators

• New York State Psychiatric Institute: lead

Study Sites (1)

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

Related Publications (8)

• Attia E, Kaplan AS, Walsh BT, Gershkovich M, Yilmaz Z, Musante D, Wang Y. Olanzapine versus placebo for out-patients with anorexia nervosa. Psychol Med. 2011 Oct;41(10):2177-82. doi: 10.1017/S0033291711000390. Epub 2011 Mar 22.

  PMID: 21426603 BACKGROUND

• Conceicao ISR, Garcia-Burgos D, de Macedo PFC, Nepomuceno CMM, Pereira EM, Cunha CM, Ribeiro CDF, de Santana MLP. Habits and Persistent Food Restriction in Patients with Anorexia Nervosa: A Scoping Review. Behav Sci (Basel). 2023 Oct 25;13(11):883. doi: 10.3390/bs13110883.

  PMID: 37998630 BACKGROUND

• Cubo E, Fernandez Jaen A, Moreno C, Anaya B, Gonzalez M, Kompoliti K. Donepezil use in children and adolescents with tics and attention-deficit/hyperactivity disorder: an 18-week, single-center, dose-escalating, prospective, open-label study. Clin Ther. 2008 Jan;30(1):182-9. doi: 10.1016/j.clinthera.2008.01.010.

  PMID: 18343255 BACKGROUND

• Steinglass JE, Fei W, Foerde K, Touzeau C, Ruggiero J, Lloyd C, Attia E, Wang Y, Walsh BT. Change in food choice during acute treatment and the effect on longer-term outcome in patients with anorexia nervosa. Psychol Med. 2024 Apr;54(6):1133-1141. doi: 10.1017/S0033291723002933. Epub 2023 Oct 2.

  PMID: 37781904 BACKGROUND

• undefined

  BACKGROUND

• El Mestikawy S, Wallen-Mackenzie A, Fortin GM, Descarries L, Trudeau LE. From glutamate co-release to vesicular synergy: vesicular glutamate transporters. Nat Rev Neurosci. 2011 Apr;12(4):204-16. doi: 10.1038/nrn2969.

  PMID: 21415847 BACKGROUND

• Bergman J, Miodownik C, Lerner PP, Miodownik E, Shulkin A, Lerner V. Donepezil as Add-on Treatment for Resistant Obsessive-Compulsive Disorder: Retrospective Case Series. Clin Neuropharmacol. 2016 Jul-Aug;39(4):194-6. doi: 10.1097/WNF.0000000000000160.

  PMID: 27223667 BACKGROUND

• Arcelus J, Mitchell AJ, Wales J, Nielsen S. Mortality rates in patients with anorexia nervosa and other eating disorders. A meta-analysis of 36 studies. Arch Gen Psychiatry. 2011 Jul;68(7):724-31. doi: 10.1001/archgenpsychiatry.2011.74.

  PMID: 21727255 BACKGROUND

MeSH Terms

Conditions

Anorexia Nervosa; Anorexia; Feeding and Eating Disorders; Habits

Interventions

Donepezil

Condition Hierarchy (Ancestors)

Mental Disorders; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Central Study Contacts

Joanna Steinglass, MD

CONTACT

646-775-6345; js1124@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Study Record Dates

• First Submitted: July 19, 2024
• First Posted: July 25, 2024
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: July 14, 2025

Record last verified: 2025-07

Locations

US (1)