Therapeutic Ketogenic Diet in Anorexia Nervosa

• ClinicalTrials.gov Identifier: NCT06000774
• Recruitment Status: Recruiting
• First Posted: August 21, 2023
• Last Update Posted: October 12, 2023
• Sponsor: University of California, San Diego
• Information provided by (Responsible Party): Guido Frank, University of California, San Diego

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Anorexia Nervosa in Remission	Other: Therapeutic Ketogenic Diet	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Subjects will complete a 14-week therapeutic ketogenic diet (TKD)
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Ketogenic Diet in Weight Recovered Anorexia Nervosa to Target Metabolism and Normalize Persistent Eating Disorder Psychopathology
• Actual Study Start Date: October 3, 2023
• Estimated Primary Completion Date: September 30, 2024
• Estimated Study Completion Date: March 31, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. To assess the safety and tolerability in individuals with anorexia nervosa who are weight recovered using weekly body weight measurements. [ Time Frame: Weekly for the duration of the study intervention (14 weeks) ]
   Weekly weights will be obtained to assess whether subjects remain within a normal weight range.
2. 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 [ Time Frame: At weeks 4, 8, 12, 14 ]
   The UKU assesses psychiatric, neurologic, autonomic, and other side effects.
3. 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 [ Time Frame: At baseline, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 3 month follow-up ]
   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.
4. Measurement of the relationship between genotype and improvement of eating disorder symptoms [ Time Frame: At baseline ]
   In order to identify potential genetic signatures that may predict response to treatment, Whole Exome Sequencing will be conducted on participants.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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
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

Contacts and Locations

Contacts

Contact: Megan Shott, BS; 848-246-5272; mshott@health.ucsd.edu

Locations

United States, California

University of California San Diego; Recruiting

San Diego, California, United States, 92121

Contact: Megan E Shott, BS 858-246-5272 mshott@health.ucsd.edu

Contact: Guido Frank, MD gfrank@health.ucsd.edu

Principal Investigator: Guido Frank, MD

Sponsors and Collaborators

University of California, San Diego

Investigators

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

More Information

Publications:

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.

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.

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.

• Responsible Party: Guido Frank, Professor, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT06000774
• Other Study ID Numbers: 807674
• First Posted: August 21, 2023
• Last Update Posted: October 12, 2023
• Last Verified: October 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Anorexia; Anorexia Nervosa; Signs and Symptoms, Digestive; Feeding and Eating Disorders; Mental Disorders