Modified Ketogenic Diet and Ketamine for Anorexia Nervosa

Case Series: A Sequenced Treatment Using a Modified Ketogenic Diet and Ketamine for Severe and Enduring Anorexia Nervosa

This Open-Label Pilot Study Aims to Determine Whether a Two-Part Sequenced Out Patient Procedure Utilizing a Modified Ketogenic Diet Followed by a Series of Titrated Ketamine Infusions Results in Improvement or Remission of Chronic Anorexia Nervosa in Adults with Symptoms of Anorexia for at Least 3 Years Despite Treatment Involving at Least 2 Different Modalities. The Hypothesis is That the Diet Addresses Core Metabolic Deficits in the "Anorexic Brain" and Primes the Response to Ketamine.

Study Overview

• Status: Completed
• Conditions: Anorexia Nervosa
• Intervention / Treatment: Drug: Ketamine Hcl 50Mg/Ml Inj

Detailed Description

Participants Who Are Deemed Eligible Will Participate in an Open-Label Clinical Trial Using a Sequenced Treatment Previously Reported in One Case Study to Result in Complete and Sustained Remission of Anorexia Nervosa for Over One Year (and Continuing).

Part 1 Involves a Group 2-Day Immersive In-Person Educational Program to Begin a Modified Ketogenic Diet, Under the Supervision of a Nutritionist Who Has Decades of Experience in Designing Ketogenic Diets for Seizure Patients. This Group Experience is Followed by a 4 Week Period of At-Home Adoption of the Diet, With Close Phone and E-Mail Follow-up.

Part 2 Involves Administration of a Series of Titrated Intravenous Ketamine Infusions Scheduled Over 2 Weeks.

During Part 1, and Part 2, There Will Be a Range of Objective and Psychological Measures To Assess Safety and Response. The Participants Will be Followed For 12 Months.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • South Windsor, Connecticut, United States, 06074
      • Lori Calabrese MD Innovative Psychiatry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults Between 18 and 65
• Anorexia Nervosa Diagnosis For at Least 3 Years
• Treatment Resistance, as Evidenced by Having Failed at Least 2 Treatments
• Body Mass Index (BMI) Greater than or Equal to 18.5
• Stable Weight for the Last 3 Months (No Consistent Change Greater than 5 Pounds)
• Abstinence From Substance Abuse for At Least 3 Months
• No Cannabis Use for At Least 3 Months
• Currently Under the Care of a Primary Care Provider (PCP)
• Participant Must Agree to have PCP Contacted by Study Staff
• Willingness to Participant in a 2-Day Program in Central Connecticut
• Identified Support Partner Who Will Attend Program
• Willingness to Have Weight Recorded and Reported by PCP or Support Partner
• Willingness to Attend 4-6 Clinic Visits For Ketamine Infusion
• Willingness to Be Contacted for Follow Up for 12 Months
• Willingness to Abide By All COVID Safety Measures

Exclusion Criteria

• Concomitant Disease (Gastroentestinal, Renal, Respiratory, Cardiac, Etc) or Any Clinically Significant Finding at Screening that Would Pose a Risk to the Participant
• Primary Carnitine Deficiency, Beta Oxidation Defects, Pyruvate Carboxylase Deficiency, Porphyria, or Treatment with Carbonic Anhydrase Inhibitors
• Bulimia Nervosa as The Primary Diagnosis
• Weight Change of Greater Than 5 Pounds in Last 3 Months
• Pregnancy
• Sexually Active Females Not Using Birth Control
• Interstitial Cystitis
• Unmanaged/Unstable Hypertenison (Greater than 140 Systolic; 90 Diastolic
• Cardiac Arrythmia
• Uncontrolled Seizure Disorder or Seizure Withen 30 Days Prior to Screening
• QTc Interval of 470 ms or Greater
• Current or Past History of Psychotic Disorder
• Active Suicidal Ideation
• Enrolled in any Clinical Trial or Used Any Investigational Agent, Device, and/or Investigational Procedure Within 30 Days Before Screening, or Does so Concurrently With this Study

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: Ketogenic Diet Adoption Followed by Ketamine Infusion; All 5 Participants Will Be Educated to Adopt a Ketogenic Diet, As Outpatient. After at Least 4 Weeks on the Diet, They Will Have A Series of Titrated Intravenous Ketamine Infusions Over A 2 Week Period	Drug: Ketamine Hcl 50Mg/Ml Inj; Racemic Ketamine Will Be Infused At A Starting Dose of 0.75 mg/kg Over A Period of 45 Minutes. The Dose Will be Titrated, Based on Clinical Signs With Changes of 0.3mg/kg Up to Maximum of 0.95 mg/kg, and Lowest Dose of 0.3 mg/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Eating Disorder Examination Questionnaire (EDE-Q) Score	A 28-item Self Report Scale that Assesses the Range and Severity of ED symptoms	Change from Baseline at 4 weeks; 8 Weeks; 3 Months; 6 Months; 9 Months; 12 Months
Change in Eating Disorder Recovery Endorsement Questionnaire (EDREQ) Score	Self Report Scale that Assesses The Indicators of Recovery	Change from Baseline at 4 Weeks, 8 Weeks, 3 Months; 6 Months, 9 Months, 12 Months
Change in Clinical Impairment Assessment (CIA) For Eating Disorders Scale	A 16-Item Self Administered Rating Scale Which Measures PsychoSocial Impairment	Change from Baseline at 4 Weeks; 8 Weeks; 3 Months; 6 Months; 9 Months;12 Months
Change in Behavior and Mood and Thinking as Measured by Interview	Qualitative Analysis of Research- Associate Administered Questionnaire	Change from Baseline at 4 Weeks, 8 Weeks, 3 Months, 6 Months, 9 Months, 12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Weight/Body Mass Index	Weight to Be Measured By Local Clinician or Support Person to Ensure Safety	Change from Baseline Biweekly for Weeks 1,2,3, and 4, Weekly for weeks 5,6,7,8.then 3 Months, 6 Months, 9 Months, 12 Months s and Prior to Every Ketamine Infusion 8 Weeks; 3 Months; 6 Months; 9 Months;12 Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breath Acetone Measure	Acetone Measured by Participant with Portable Breath Acetone Meter	Change from Baseline Daily Week 1,2,3, and 4 ,8 Weeks, 3 Months, 6 Months, 9 Months, 12 Months
Brief 24- Hour Food Recall	Obtained by Research Associate	Change from Baseline Weeks1,2,3,4 then, 8 Weeks, 3 Months, 6 Months, 9 Months 12 Months
Change in Food Preference as Assessed by The Geiselman Food Preference Questionnaire	Self Administered Questionnaire	Change from Baseline at 4 Weeks, 8 Weeks, then 3 Months, 6 Months, 9 Months 12 Months
Change in Depressive Symptoms as Assessed by Patient Health Questionnaire	A 9 Item Self Administered Questionnaire	Change from Baseline at Week 4, 5, 6, and 3 Months, 6 Months, 9 Months 12 Mos

Collaborators and Investigators

• Sponsor: Homeostasis Therapeutics, LLC
• Investigators: Principal Investigator: Lori Calabrese, MD, Innovative Psychiatry So Windsor; Principal Investigator: Lori Calabrese, MD, Innovative Psychiatry, So Windsor

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2021
• Primary Completion (Actual): July 26, 2022
• Study Completion (Actual): July 26, 2022

Study Registration Dates

• First Submitted: January 12, 2021
• First Submitted That Met QC Criteria: January 15, 2021
• First Posted (Actual): January 19, 2021

Study Record Updates

• Last Update Posted (Actual): November 4, 2022
• Last Update Submitted That Met QC Criteria: November 1, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Signs and Symptoms, Digestive; Feeding and Eating Disorders; Anorexia; Anorexia Nervosa; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 01-2020 ANKK

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