Ketogenic and Nutritional Interventions for First Episode Bipolar Disorder

NCT ID: NCT06221852

Last Updated: 2025-11-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-12
• Study Completion Date: 2027-12-30

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.

Detailed Description

Several lines of evidence show energy metabolism and redox dysregulation in bipolar disorder and psychotic disorders. Ketogenic interventions targeting energy metabolism are promising therapeutic approaches to improve mood and psychosis in bipolar disorder and other psychotic disorders. Early intervention is also critical to helping people achieve their goals for recovery after a first episode. Investigators aim to use multimodal imaging and metabolic measures to study the effects of a ketogenic diet intervention on energy metabolism and psychiatric symptoms in individuals with first episode bipolar disorder and schizoaffective disorder. This 12-week randomized controlled trial will assess the benefits of a ketogenic diet in combination with treatment as usual compared to a standard diet. Investigators will measure the effects of nutritional ketosis on brain redox and energy metabolism and other neurometabolic markers using magnetic resonance spectroscopy. Furthermore, investigators will measure the effects of the ketogenic diet on mood and psychotic symptoms and metabolic measures such as insulin resistance.

Conditions

Bipolar I Disorder; Psychosis; Schizoaffective Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ketogenic diet arm

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.

Group Type: ACTIVE_COMPARATOR

Ketogenic diet

Intervention Type: 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.

Dietary Guidelines for Americans arm

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.

Group Type: ACTIVE_COMPARATOR

Dietary Guidelines for Americans

Intervention Type: 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).

Interventions

Ketogenic diet

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.

Intervention Type: OTHER

Dietary Guidelines for Americans

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).

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baszucki Family Foundation

UNKNOWN

Sponsor Role: collaborator

Mclean Hospital

OTHER

Sponsor Role: lead

Responsible Party

Virginie-Anne Chouinard, MD

Psychiatrist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Virginie-Anne Chouinard, MD

Role: PRINCIPAL_INVESTIGATOR

Mclean Hospital

Locations

McLean Hospital

Belmont, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jacey Anderson, B.A.

Role: CONTACT

janderson75@mclean.harvard.edu

617-855-3988

Virginie-Anne Chouinard, MD

Role: CONTACT

vchouinard@mclean.harvard.edu

Facility Contacts

Jacey Anderson, B.A.

Role: primary

janderson75@mclean.harvard.edu

Other Identifiers

2023P002849

Identifier Type: -

Identifier Source: org_study_id