Ketogenic and Nutritional Interventions for First Episode Bipolar Disorder

Mass General Brigham

Status: Enrolling

Conditions: Psychosis; Bipolar I Disorder; Schizoaffective Disorder

Treatments: Other: Dietary Guidelines for Americans; Other: Ketogenic diet

Study type: Interventional

Funder types: Other

Identifiers

NCT06221852

2023P002849

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 estimated patients

Sex: All

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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50 participants in 2 patient groups

Ketogenic diet arm

Active Comparator group

Description:

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.

Treatment:

Other: Ketogenic diet

Dietary Guidelines for Americans arm

Active Comparator group

Description:

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.

Treatment:

Other: Dietary Guidelines for Americans