Ketogenic Metabolic Therapy in Schizophrenia, Bipolar Disorder, Major Depressive Disorder: Deep Omic Profiling

NCT06748950 | Not Yet Recruiting

• 1 other identifier: 76425
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this randomized clinical trial is to be adequately powered to evaluate the effect of ketogenic metabolic therapy on the quality of life in serious mental illness, schizophrenia, bipolar disorder, major depressive disorder.

Conditions

Schizophrenia; Schizophrenia and Related Disorders; Bipolar Disorder; Bipolar and Related Disorders; Major Depressive Disorder; Major Depression Severe; Ketogenic Dieting; Ketosis; Metabolic Disease; Metabolic Syndrome

Keywords

Mental Illness; Multiomics; Multi-omics; Omics Profiling

Outcome Measures

Primary Outcomes (3)

• WHO-5 Well-being Index

  Change in general well-being from baseline. Self reported to measure quality of life. Assessed on 5-items, scored from 0-5 on each item, with higher scores indicating better quality of life.

  Baseline through study completion, an average of 12 weeks (Arm 1: Ketogenic Diet Only) or 24 weeks (Arm 2: DAU-Ketogenic Diet Crossover).

• Functioning Assessment Short Test (FAST)

  Change in quality of life from baseline. Self reported and assessed on 24-items regarding difficulties in the experiences described. Scored from 0-3 on each item, with lower composite scores indicating better quality of life.

  Baseline through study completion, an average of 12 weeks (Arm 1: Ketogenic Diet Only) or 24 weeks (Arm 2: DAU-Ketogenic Diet Crossover).

• Quality of Life Scale (QIDS)

  Change in severity of depression from baseline. Self reported on 16 items with a composite score range of 0-27 (0= no depression, 27 = very severe depression).

  Baseline through study completion, an average of 12 weeks (Arm 1: Ketogenic Diet Only) or 24 weeks (Arm 2: DAU-Ketogenic Diet Crossover).

Secondary Outcomes (28)

• Cambridge Cognition (CANTAB Assessment)

  Baseline through study completion, an average of 12 weeks (Arm 1: Ketogenic Diet Only) or 24 weeks (Arm 2: DAU-Ketogenic Diet Crossover).

• Quality of Life in Neurological Disorders (Neuro-QOL, Cognitive Function)

  Baseline through study completion, an average of 12 weeks (Arm 1: Ketogenic Diet Only) or 24 weeks (Arm 2: DAU-Ketogenic Diet Crossover).

• Brief Psychiatric Assessment Scale (BPRS)

  Screening; Baseline through study completion, an average of 12 weeks (Arm 1: Ketogenic Diet Only) or 24 weeks (Arm 2: DAU-Ketogenic Diet Crossover).

• Patient Health Questionnaire (PHQ-9)

  Screening; Baseline through study completion, an average of 12 weeks (Arm 1: Ketogenic Diet Only) or 24 weeks (Arm 2: DAU-Ketogenic Diet Crossover).

• Clinical Global Impressions Scale (CGI)/ Clinical Mood Monitoring

  Screening; Baseline through study completion, an average of 12 weeks (Arm 1: Ketogenic Diet Only) or 24 weeks (Arm 2: DAU-Ketogenic Diet Crossover).

Study Arms (2)

Arm 1: Ketogenic Diet Only

EXPERIMENTAL

Participants will follow 12 weeks of the ketogenic diet, with monitoring of physical and psychological health and coaching support.

Other: LCHF Ketogenic Diet

Arm 2: DAU- Ketogenic Diet Crossover

EXPERIMENTAL

Participants will follow 12 weeks of their usual diet (Diet-as-Usual, DAU). Then, participants will crossover and follow 12 weeks of the ketogenic diet. Monitoring of physical and psychological health and coaching support will occur throughout participation.

Other: LCHF Ketogenic Diet; Other: Diet-as-Usual (DAU)

Interventions

LCHF Ketogenic Diet OTHER

Low Carbohydrate, Moderate Protein, High Fat (LCHF) Ketogenic Dietary Intervention for 12 weeks

Arm 1: Ketogenic Diet Only; Arm 2: DAU- Ketogenic Diet Crossover

Diet-as-Usual (DAU) OTHER

Participant's usual diet

Arm 2: DAU- Ketogenic Diet Crossover

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• diagnosed with bipolar disorder (BD), major depressive disorder (MDD), and or schizophrenia
• For individuals diagnosed with bipolar disorder (BD):
• Meet DSM V criteria for BD (any subtype)
• Not mild
• \>40 on BPRS
• clinically stable (with no hospitalization for past 3 months)
• For individuals diagnosed with major depressive disorder (MDD):
• Not mild
• PHQ-9 \> 10
• clinically stable (with no hospitalization for past 3 months)
• For individuals diagnosed with schizophrenia:
• Meet DSM V criteria for schizophrenia (any subtype)
• Not mild
• \>40 on BPRS
• clinically stable (with no hospitalization for past 3 months)

You may not qualify if:

• has started the ketogenic diet or was in ketosis within 3 months of wanting to enroll
• pregnant or nursing
• insulin dependent
• comorbidity of developmental delay
• in a current severe mood or psychotic state when entering the study that would prohibit compliance with study visits or dietary programs.
• any one who has been hospitalized or taken clozapine at doses above 550mg over the past 3 months
• inability to complete baseline measurements
• severe renal or hepatic insufficiency
• cardiovascular dysfunction, including diagnosis of:
• Congestive heart failure
• Angina
• Arrhythmias
• Cardiomyopathy
• Valvular heart disease
• active substance abuse with illicit drugs or alcohol and/or current diagnosis of a Substance Use Disorder (Abuse or Dependence, as defined by DSM-IV-TR), with the exception of nicotine or cannabis dependence

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Palo Alto, California, 94304, United States

Location

Related Publications (1)

• Leucht S, Kane JM, Kissling W, Hamann J, Etschel E, Engel R. Clinical implications of Brief Psychiatric Rating Scale scores. Br J Psychiatry. 2005 Oct;187:366-71. doi: 10.1192/bjp.187.4.366.

  PMID: 16199797 BACKGROUND

MeSH Terms

Conditions

Schizophrenia; Bipolar Disorder; Bipolar and Related Disorders; Depressive Disorder, Major; Ketosis; Metabolic Diseases; Metabolic Syndrome; Mental Disorders

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mood Disorders; Depressive Disorder; Acidosis; Acid-Base Imbalance; Nutritional and Metabolic Diseases; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders

Study Officials

• Shebani Sethi, MD, ABOM

  Stanford University

  PRINCIPAL INVESTIGATOR

• Michael Snyder, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Coordinator

CONTACT

(650) 725-0169; jessili@stanford.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: December 14, 2024
• First Posted: December 27, 2024
• Study Start: July 1, 2025
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: May 16, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)