Therapeutic Ketogenic Diet in Anorexia Nervosa

Ketogenic Diet in Weight Recovered Anorexia Nervosa to Target Metabolism and Normalize Persistent Eating Disorder Psychopathology

This study will investigate the effects of therapeutic ketogenic diet (TKD) on eating behavior including drive to restrict, body dissatisfaction, mood and anxiety in individuals with anorexia nervosa who have been weight normalized (body mass index of 17.5 or greater) but continue to struggle with eating disorder behaviors including a high drive for thinness and body dissatisfaction.

Study Overview

• Status: Recruiting
• Conditions: Anorexia Nervosa in Remission
• Intervention / Treatment: Other: Therapeutic Ketogenic Diet

Detailed Description

For this 14-week study, the investigator will recruit twenty individuals with anorexia nervosa who have been weight normalized but continue to have high impairment from the illness with a high (2 standard deviations above average) drive for thinness and body dissatisfaction and a high drive for food restriction and thus are at high risk for full relapse. Study participants will be carefully assessed and oriented to the ketogenic diet according to the procedures in our small previous trial (Calabrese, et al., 2022). The study will be conducted in a university medical environment, showing feasibility and safety in a typical medical setting. A commercial supplier will provide the ketogenic diet. After ketosis induction over two weeks, study participants will be assessed weekly for ketosis and mood, anxiety, and eating disorder symptoms.

Primary Objective 1 is to test the effects of ketogenic diet in individuals with anorexia nervosa who are weight recovered but continue to suffer severely from drive for thinness and are at very high relapse risk. Participants will be evaluated for tolerability of the study and weight trajectory. Primary Objective 2 is to assess improvement in AN symptoms and behaviors in relation to the ketogenic diet over a 12-week course. Participants will be assessed for specific symptoms such as drive for thinness and body dissatisfaction, fear of eating and weight gain. Primary Objective 3 is to assess the underlying genetic basis for the treatment effect of the ketogenic diet.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Megan Shott, BS; Phone Number: 848-246-5272; Email: mshott@health.ucsd.edu

Study Locations

• United States
  • California
    • San Diego, California, United States, 92121
      • Recruiting
      • University of California San Diego
      • Contact: Megan E Shott, BS; Phone Number: 858-246-5272; Email: mshott@health.ucsd.edu
      • Contact: Guido Frank, MD; Email: gfrank@health.ucsd.edu
      • Principal Investigator: Guido Frank, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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
3. Persons, aged 18 to 45 years
4. History of anorexia nervosa according to DSM-5 criteria
5. Weight recovered at the time of study inclusion (body mass index > 17.5 kg/m2)
6. Greater or equal to 2 standard deviations scores of eating disorder-relevant behaviors on the Eating Disorder Inventory-3 and Eating Disorder Examination Questionnaire
7. The following types of psychiatric medications are allowed: antidepressant, anxiolytic, atypical antipsychotic, mood stabilizers
8. English is primary spoken language

Exclusion Criteria:

1. Pregnancy or lactation
2. Electrolyte, blood count, kidney function or liver function abnormalities
3. Psychosis
4. Neurocognitive disorders including dementias or traumatic brain injury that is symptomatic
5. Current alcohol use disorder (AUD) or substance use disorder (SUD) according to DSM-5 criteria
6. Uncontrolled hypertension
7. Hepatic impairment (Class-Pugh b or c)
8. Diabetes mellitus
9. Family history of porphyria
10. History of recent heart attack, vascular disease, or any other current acute medical conditions as determined by the principal investigator
11. Inability or unwillingness to adhere to the TKD diet for the duration of the study
12. Blind or illiterate individuals

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Therapeutic Ketogenic Diet; A 2-week therapeutic ketogenic diet (TKD) induction will be implemented to establish nutritional ketosis (the goal are BHB blood levels of 0.5-3.0 millimoles per liter [mmol/L]). After establishing the ketotic state, study participants will continue TKD for 12 weeks.	Other: Therapeutic Ketogenic Diet; therapeutic ketogenic diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the safety and tolerability in individuals with anorexia nervosa who are weight recovered using weekly body weight measurements.	Weekly weights will be obtained to assess whether subjects remain within a normal weight range.	Weekly for the duration of the study intervention (14 weeks)
To assess the safety and tolerability in individuals with anorexia nervosa who are weight recovered using the Committee of Clinical Investigations UKU-Side Effect Scale	The UKU assesses psychiatric, neurologic, autonomic, and other side effects.	At weeks 4, 8, 12, 14
Measurement of drive for weight loss, fear of weight gain and body image distortion using the Eating Disorder Examination Questionnaire (EDEQ) Global Score, EDEQ Eating Restraint Score, and EDEQ Weight Concern	The Eating Disorders Examination Questionnaire a self report assessment that measures core eating disorder symptoms. Subjects will complete this measure at the beginning and end of the study and weekly throughout the 14-week intervention and the investigator will measure the change in scores. The EDE Global, Eating Restraint, and Weight Concern scales have a range of 0 to 6 where higher scores mean worse outcome.	At baseline, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 3 month follow-up
Measurement of the relationship between genotype and improvement of eating disorder symptoms	In order to identify potential genetic signatures that may predict response to treatment, Whole Exome Sequencing will be conducted on participants.	At baseline

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Investigators: Principal Investigator: Guido Frank, MD, University of California, San Diego

Publications and helpful links

General Publications

• Frank GKW, Shott ME, Stoddard J, Swindle S, Pryor TL. Association of Brain Reward Response With Body Mass Index and Ventral Striatal-Hypothalamic Circuitry Among Young Women With Eating Disorders. JAMA Psychiatry. 2021 Oct 1;78(10):1123-1133. doi: 10.1001/jamapsychiatry.2021.1580.
• Scolnick B, Zupec-Kania B, Calabrese L, Aoki C, Hildebrandt T. Remission from Chronic Anorexia Nervosa With Ketogenic Diet and Ketamine: Case Report. Front Psychiatry. 2020 Jul 30;11:763. doi: 10.3389/fpsyt.2020.00763. eCollection 2020.
• Frank GKW, Shott ME, DeGuzman MC. The Neurobiology of Eating Disorders. Child Adolesc Psychiatr Clin N Am. 2019 Oct;28(4):629-640. doi: 10.1016/j.chc.2019.05.007. Epub 2019 Jul 4.
• Dignon A, Beardsmore A, Spain S, Kuan A. 'Why I won't eat': patient testimony from 15 anorexics concerning the causes of their disorder. J Health Psychol. 2006 Nov;11(6):942-56. doi: 10.1177/1359105306069097.
• Calabrese L, Scolnick B, Zupec-Kania B, Beckwith C, Costello K, Frank GKW. Ketogenic diet and ketamine infusion treatment to target chronic persistent eating disorder psychopathology in anorexia nervosa: a pilot study. Eat Weight Disord. 2022 Dec;27(8):3751-3757. doi: 10.1007/s40519-022-01455-x. Epub 2022 Aug 23.

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2023
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: August 14, 2023
• First Submitted That Met QC Criteria: August 14, 2023
• First Posted (Actual): August 21, 2023

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Signs and Symptoms, Digestive; Feeding and Eating Disorders; Anorexia; Anorexia Nervosa
• Other Study ID Numbers: 807674

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No