Ketogenic and Nutritional Interventions for First Episode Bipolar Disorder

This study is a randomized clinical trial looking at how a ketogenic diet, along with your usual treatment, affects brain energy and symptoms in people with first-episode bipolar I disorder or schizoaffective disorder. It compares the ketogenic diet (high fat, low carb) to the Dietary Guidelines for Americans diet (a standard healthy diet). Researchers will measure changes in brain energy markers (like NAD+/NADH ratio and creatine kinase) and insulin resistance after 12 weeks to see if the ketogenic diet is helpful. You may be able to join if you are 18-45 years old, have a recent diagnosis of bipolar I disorder or schizoaffective disorder, and can follow one of the study diets. The current recruitment status is unclear.

Study design
This is a randomized controlled trial aiming to enroll 50 participants. It compares a ketogenic diet to a standard diet.
What's involved
You would follow a specific diet (either ketogenic or standard) for 12 weeks. The study will involve measurements of brain energy and metabolic markers.
Compensation
Not stated in the trial record.
Follow-up
Participants will be followed for 12 weeks, which is when the primary outcomes are measured.

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NCT06221852

Ketogenic and Nutritional Interventions for First Episode Bipolar Disorder

Recruiting
NAAges 18–45InterventionalTreatment
Mclean Hospital
~50 participants
Updated 2026-08-17 on ClinicalTrials.gov
What's tested:Ketogenic dietDietary Guidelines for Americans

At a glance

Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Change in brain redox nicotinamide adenine dinucleotide metabolites ratio (NAD+/NADH)
Measured over 12 weeks
+6 more outcomes measured
Bipolar I Disorder
Psychosis
Schizoaffective Disorder
1 sites across 1 states
Massachusetts1
  • Virginie-Anne Chouinard, MD · PRINCIPAL_INVESTIGATOR · Mclean Hospital

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Eligibility criteria

Inclusion

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

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
  • Change in brain redox nicotinamide adenine dinucleotide metabolites ratio (NAD+/NADH)12 weeks

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

  • Change in brain creatine kinase forward reaction rate (kf)12 weeks

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

  • Change in insulin resistance12 weeks

    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.

  • Change in psychotic symptoms12 weeks

    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.

  • Change in depressive symptoms12 weeks

    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.

  • Change in mania symptoms12 weeks

    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.

  • Change in Clinical Global Impression (CGI) Scale12 weeks

    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.