Therapeutic Ketogenic Diet in Anorexia Nervosa

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Anorexia Nervosa in Remission

Intervention / Treatment
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* Other: Therapeutic Ketogenic Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Persons, aged 18 to 45 years History of anorexia nervosa according to DSM-5 criteria Weight recovered at the time of study inclusion (body mass index > 17.5 kg/m2) Greater or equal to 2 standard deviations scores of eating disorder-relevant behaviors on the Eating Disorder Inventory-3 and Eating Disorder Examination Questionnaire The following types of psychiatric medications are allowed: antidepressant, anxiolytic, atypical antipsychotic, mood stabilizers English is primary spoken language Exclusion Criteria: Pregnancy or lactation Electrolyte, blood count, kidney function or liver function abnormalities Psychosis Neurocognitive disorders including dementias or traumatic brain injury that is symptomatic Current alcohol use disorder (AUD) or substance use disorder (SUD) according to DSM-5 criteria Uncontrolled hypertension Hepatic impairment (Class-Pugh b or c) Diabetes mellitus Family history of porphyria History of recent heart attack, vascular disease, or any other current acute medical conditions as determined by the principal investigator Inability or unwillingness to adhere to the TKD diet for the duration of the study Blind or illiterate individuals

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Subjects will complete a 14-week therapeutic ketogenic diet (TKD)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Therapeutic Ketogenic Diet<br>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<br>* therapeutic ketogenic diet<br>|

What is the study measuring?
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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 |