Recruiting

Ketogenic Interventions

Sponsor:

Mclean Hospital

Code:

NCT06221852

Conditions

Bipolar I Disorder

Psychosis

Schizoaffective Disorder

Eligibility Criteria

Sex: All

Age: 18 - 45

Healthy Volunteers: Not accepted

Interventions

Ketogenic diet

Dietary Guidelines for Americans

Study Details

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

Study ID

NCT06221852

Start date

Mar 12, 2024

Status verified date

Nov, 2025

Completion date

Dec 30, 2027

Anticipated

Primary completion date

Sep 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 45

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

50 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: 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.

active comparator: 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.

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.

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).

Primary outcome measure

  • Change in brain redox nicotinamide adenine dinucleotide metabolites ratio (NAD+/NADH) [ Time Frame: 12 weeks ]
  • Change in brain creatine kinase forward reaction rate (kf) [ Time Frame: 12 weeks ]
  • Change in insulin resistance [ Time Frame: 12 weeks ]
  • Change in psychotic symptoms [ Time Frame: 12 weeks ]
  • Change in depressive symptoms [ Time Frame: 12 weeks ]
  • Change in mania symptoms [ Time Frame: 12 weeks ]
  • Change in Clinical Global Impression (CGI) Scale [ Time Frame: 12 weeks ]

Central Contacts and Locations

Central contacts

Kaitlin Shannon, B.A.

617-855-2410kshannon6@mgb.org

Virginie-Anne Chouinard, MD

vchouinard@mclean.harvard.edu

Locations

McLean Hospital

Recruiting

Belmont, Massachusetts, United States, 02478

Contacts

Kaitlin Shannon, B.A.

kshannon6@mgb.org

Principal Investigator:

Virginie-Anne Chouinard, MD

More Information

Sponsor

Mclean Hospital

Last update posted

Aug 17, 2026

Last verified

Nov, 2025

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Mclean Hospital on 2026-08-17.