Ketogenic and Nutritional Interventions for First Episode Bipolar Disorder

NCT06221852 | Recruiting

• 1 other identifier: 2023P002849
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, controlled clinical trial to assess the effects of the ketogenic diet in combination with treatment as usual on brain energy metabolism and psychiatric symptoms in individuals with first episode bipolar disorder and schizoaffective disorder.

Conditions

Bipolar I Disorder; Psychosis; Schizoaffective Disorder

Keywords

First episode psychosis; Ketogenic Diet; Keto; Brain energy metabolism; Insulin resistance; Schizoaffective Disorder; Bipolar Disorder; Magnetic resonance spectroscopy (MRS); Redox; Creatine kinase

Outcome Measures

Primary Outcomes (7)

• Change in brain redox nicotinamide adenine dinucleotide metabolites ratio (NAD+/NADH)

  Change from baseline to week 12 in NAD+/NADH as measured by in vivo phosphorus magnetic resonance spectroscopy (31P-MRS).

  12 weeks

• Change in brain creatine kinase forward reaction rate (kf)

  Change from baseline to week 12 in creatine kinase forward reaction rate (kf) as measured by 31P magnetization transfer (MT) MRS.

  12 weeks

• Change in insulin resistance

  Change from baseline to week 12 of insulin resistance measured using the homeostatic model assessment of insulin resistance (HOMA-IR) using fasting blood glucose and insulin levels.

  12 weeks

• Change in psychotic symptoms

  Change from baseline to week 12 in Positive and Negative Syndrome Scale (PANSS) total score. Scores range from 30-210; a higher score indicates a higher level of psychotic symptoms.

  12 weeks

• Change in depressive symptoms

  Change from baseline to week 12 in Hamilton Rating Scale for Depression (HAM-D) total score. Scores range from 0-52; a higher score indicates a higher level of depression.

  12 weeks

• Change in mania symptoms

  Change from baseline to week 12 in Young Mania Rating Scale (YMRS) total score. Scores range from 0-60. A higher score indicates a more severe illness.

  12 weeks

• Change in Clinical Global Impression (CGI) Scale

  Change from baseline to week 12 in Clinical Global Impression (CGI) Scale. Scores range from 1-7; a higher score indicates higher severity of illness.

  12 weeks

Secondary Outcomes (21)

• Change in body weight

  12 weeks

• Change in glycated hemoglobin (Hemoglobin A1c) level

  12 weeks

• Change in triglyceride levels

  12 weeks

• Change in low-density lipoprotein (LDL) levels

  12 weeks

• Change in high-density lipoprotein (HDL) levels

  12 weeks

Other Outcomes (8)

• Change in World Health Organization Disability Assessment Schedule (WHODAS) score

  12 weeks

• Change in World Health Organization Quality of Life (WHOQOL) score

  12 weeks

• Change in Extrapyramidal Symptom Rating Scale (ESRS) total score

  12 weeks

Study Arms (2)

Ketogenic diet arm

ACTIVE COMPARATOR

Eligible participants assigned to the ketogenic diet arm will be asked to follow the ketogenic diet (KD) for 12 weeks in addition to any ongoing medications (e.g., mood stabilizers and/or second-generation antipsychotics). Participants will receive weekly and as needed diet counseling from a registered dietician. Participants will be asked to monitor and report their blood ketone levels each day via a finger-prick device provided by the study team. Participants have the ability to opt into an optional open label phase where they can continue on the ketogenic diet with the daily finger pricks for another 12 weeks after the 12-week main study.

Other: Ketogenic diet

Dietary Guidelines for Americans arm

ACTIVE COMPARATOR

Eligible participants assigned to the Dietary Guidelines for Americans (DGA) arm will adhere to the Dietary Guidelines for Americans in addition to any ongoing medications (e.g., mood stabilizers and/or second-generation antipsychotics). Participants will receive weekly and as needed diet counseling from a registered dietician. Participants will be asked to monitor and report their blood ketone levels each day via a finger-prick device provided by the study team. Participants have the ability to opt into an optional open label phase where they can switch to the ketogenic diet with the daily finger pricks for 12 weeks after the 12-week main study.

Other: Dietary Guidelines for Americans

Interventions

Ketogenic diet OTHER

The ketogenic diet (KD) is a normo-caloric diet composed of high-fat, low carbohydrate, and adequate protein intake. The KD will consist of 3 meals a day plus snacks, targeting 75-80% fat, 13-18% protein, 7% carbohydrates.

Ketogenic diet arm

Dietary Guidelines for Americans OTHER

Dietary Guidelines for Americans diet is a normo-caloric diet consisting of 3 meals a day plus snacks, emphasizing nutrient dense foods to meet food group needs (85% of calories), and limits foods and beverages higher in added sugars and saturated fat (15% of calories).

Dietary Guidelines for Americans arm

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Between the ages of 18 and 45.
• Ability to adhere to study diets.
• Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnosis of bipolar I disorder or schizoaffective disorder with onset of illness in the last 7 years.
• Must have a stable psychiatric disorder with no change in psychiatric medications within the past 2 weeks of screening
• Must not be expected to require addition of any new psychiatric medications during the 12-week duration of the study.

You may not qualify if:

• Unable to sign informed consent
• Contraindication to magnetic resonance (MR) scan (including claustrophobia)
• Unstable medical illness (including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease)
• Current DSM-5 substance use disorder
• Currently pregnant, nursing, or of childbearing potential and not using a medically accepted means of contraception
• Have a body weight of over 350 lbs or a body mass index (BMI) \<20
• Score above 15 on the Young Mania Rating Scale (YMRS)
• History of significant head injury
• Current cancer diagnosis
• Current diagnosis of type 1 or type 2 Diabetes Mellitus
• History of gastric bypass surgery or any weight loss surgery
• Concomitant treatment with Propofol
• Familial hypercholesterolemia

Sponsors & Collaborators

• Mclean Hospital: lead
• Baszucki Family Foundation: collaborator

Study Sites (1)

McLean Hospital

Belmont, Massachusetts, 02478, United States

RECRUITING

MeSH Terms

Conditions

Psychotic Disorders; Insulin Resistance; Bipolar Disorder

Interventions

Diet, Ketogenic; Nutrition Policy

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Bipolar and Related Disorders; Mood Disorders

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Health Policy; Public Policy; Social Control Policies; Policy; Health Care Economics and Organizations

Study Officials

• Virginie-Anne Chouinard, MD

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jacey Anderson, B.A.

CONTACT

617-855-3988; janderson75@mclean.harvard.edu

Virginie-Anne Chouinard, MD

CONTACT

vchouinard@mclean.harvard.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: Psychiatrist

Study Record Dates

• First Submitted: January 11, 2024
• First Posted: January 24, 2024
• Study Start: March 12, 2024
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: November 5, 2025

Record last verified: 2025-11

Locations

US (1)