Clinical trial NCT06518941: An Open Trial of a Novel Pharmacotherapy for Habit Modification in Anorexia Nervosa
Official title: An Open Trial of a Novel Pharmacotherapy for Habit Modification in Anorexia Nervosa
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Anorexia Nervosa
Keywords: anorexia
anorexia nervosa
donepezil
eating disorders
acetylcholinesterase inhibitor
Acetylcholine
habit
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
First posted: 2024-07-25
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

Detailed description: Anorexia nervosa (AN) is a serious mental illness affecting up to 4% of women in the United States, with a chronic course and a mortality rate 6 times that expected for young women (Arcelus et al., 2011). The core, salient behavior in AN is maladaptive food restriction that persists even after full weight restoration treatment (Steinglass et al., 2023). Pharmacologic approaches to the treatment of AN, to date, have attempted to capitalize on side effect profiles (e.g., weight gain) or efficacy in related disorders (e.g., depression) but have yielded disappointing results (Muratore and Attia, 2022). This program of research leverages advances in mechanism research, which has identified the importance of habit systems in AN (Conceição et al., 2023), to test whether a medication can target habitual restrictive intake and thereby help patients with AN.

Donepezil is an acetylcholinesterase inhibitor and an FDA-approved medication that has been shown to reverse habitual behaviors like excessive exercise and food restriction in a rodent model of AN. Donepezil has been studied for its potential effect in mitigating compulsive, habit-like symptoms in other clinical populations, with no adverse events (Bergman et al., 2016; Cubo et al., 2008). These data suggest that donepezil may be effective in reducing maladaptive behaviors in compulsive disorders. There is no control product in this study.

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. The target dose of 5 mg/day is lower than the approved dose for dementia and the dose used in a study of adults with Obsessive Compulsive Disorder (OCD) (Bergman et al., 2016). Doses may be lowered from those recommended by the protocol if side effects are significant.

The primary objective of this study is to test the feasibility and tolerability of donepezil among patients with AN. The exploratory objectives are to test the utility of donepezil to modify the habitual behaviors characteristic of AN.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. Score of High Risk on the Columbia Suicide Severity Scale (C-SSRS).
2. Pregnancy (Serum pregnancy test on admission).
3. Current diagnosis of schizophrenia, schizophreniform disorder, bipolar (type I), or substance use disorder (SCID).
4. Bradycardia (below 60 bpm) (vital signs measurement by the clinical team)
5. Corrected QT interval (QTc) greater than 480 ms at baseline (EKG).
6. Antipsychotic medication (antidepressants at a stable dose are allowed) (clinical interview).
7. Known allergic reactions to components of the donepezil (e.g., known hypersensitivity to donepezil hydrochloride) (clinical interview).
8. History of peptic ulcer disease (clinical interview).
9. History of arrhythmia (clinical interview).

Primary outcomes:
measure: Side Effects Form
timeFrame: From enrollment to the end of treatment at 8 weeks
measure: Clinical Global Impressions Scale
timeFrame: From enrollment to the end of treatment at 8 weeks
Secondary outcomes:
measure: Self-Report Habit Index
timeFrame: From enrollment to the end of treatment at 8 weeks
measure: Food Choice Task
timeFrame: From enrollment to the end of treatment at 8 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: New York State Psychiatric Institute
state: New York
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: undefined
citation: 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.
citation: 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.
citation: 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.