Open Label Extension Study of NCT06221852

Open Label Extension Study of NCT06221852 of the Ketogenic Diet in Participants With First Episode Bipolar Disorder.

This is a 12-week open-label extension study for participants completing study NCT06221852.

Study Overview

• Status: Enrolling by invitation
• Conditions: Schizoaffective Disorder; Psychosis; Bipolar I Disorder
• Intervention / Treatment: Other: Ketogenic diet

Detailed Description

In this 12-week single arm open label extension study of NCT06221852, the investigators aim to assess the longer term efficacy, safety and tolerability of the ketogenic diet in participants completing the randomized study phase of NCT06221852. Investigators will assess longer term effects on energy metabolism, insulin resistance and psychiatric symptoms.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Belmont, Massachusetts, United States, 02487
      • McLean Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants who met original entry criteria in, and completed, the randomized 12-week study of NCT06221852.

Exclusion Criteria:

-No longer meeting original entry criteria from the randomized 12-week study of NCT06221852.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ketogenic diet; Participants 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 diet counseling from a registered dietitian. Participants will be asked to monitor and report their blood ketone and glucose levels each day via a finger-prick device provided by the study team.

Other: 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.; Other Names: Keto diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in brain redox nicotinamide adenine dinucleotide metabolites ratio (NAD+/NADH)	Change from baseline to week 24 in NAD+/NADH as measured by in vivo phosphorus magnetic resonance spectroscopy (31P-MRS).	24 weeks
Change in brain creatine kinase forward reaction rate (kf)	Change from baseline to week 24 in creatine kinase forward reaction rate (kf) as measured by 31P magnetization transfer (MT) MRS.	24 weeks
Change in insulin resistance	Change from baseline to week 24 of insulin resistance measured using the homeostatic model assessment of insulin resistance (HOMA-IR) using fasting blood glucose and insulin levels.	24 weeks
Change in psychotic symptoms	Change from baseline to week 24 in Positive and Negative Syndrome Scale (PANSS) total score. Scores range from 30-210; a higher score indicates a higher level of psychotic symptoms.	24 weeks
Change in depressive symptoms	Change from baseline to week 24 in Hamilton Rating Scale for Depression (HAM-D) total score. Scores range from 0-52; a higher score indicates a higher level of depression.	24 weeks
Change in mania symptoms	Change from baseline to week 24 in Young Mania Rating Scale (YMRS) total score. Scores range from 0-60. A higher score indicates a more severe illness.	24 weeks
Change in Clinical Global Impression (CGI) Scale	Change from baseline to week 24 in Clinical Global Impression (CGI) Scale. Scores range from 1-7; a higher score indicates higher severity of illness.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in body weight	Change from baseline to week 24 in participant body weight in kilograms, as measured using a standing scale.	24 weeks
Change in glycated hemoglobin (Hemoglobin A1c) level	Change from baseline to week 24 in fasting Hemoglobin A1c level.	24 weeks
Change in triglyceride levels	Change from baseline to week 24 in fasting triglyceride levels.	24 weeks
Change in low-density lipoprotein (LDL) levels	Change from baseline to week 24 in fasting LDL levels	24 weeks
Change in high-density lipoprotein (HDL) levels	Change from baseline to week 24 in fasting HDL levels	24 weeks
Change in high-sensitivity C-reactive protein (hs-CRP) levels	Change from baseline to week 24 in fasting hs-CRP levels.	24 weeks
Change in brain gamma-aminobutyric acid (GABA) concentration	Change from baseline to week 24 in GABA concentration measured by proton magnetic resonance spectroscopy.	24 weeks
Change in brain glutamate metabolite concentration	Change from baseline to week 24 in glutamate metabolite concentration measured by proton magnetic resonance spectroscopy.	24 weeks
Change in brain glutathione (GSH)	Change from baseline to week 24 in brain GSH measured by proton magnetic resonance spectroscopy.	24 weeks
Change in brain Phosphocreatine (PCr)	Changes from baseline to week 24 in PCr concentration as measured by in vivo 31P-MRS.	24 weeks
Change in brain pH	Change from baseline to week 24 in pH as measured by in vivo 31P MRS	24 weeks
Change in brain inorganic phosphate concentration	Change from baseline to week 24 in inorganic phosphate (Pi) concentration as measured by in vivo 31P MRS.	24 weeks
Change in adverse events	Change from baseline to week 24 in adverse events.	24 weeks
Change in anxiety symptoms	Change from baseline to week 24 from baseline to week 12 in Hamilton Anxiety Rating Scale (HAM-A) total score. Scores range from 0 - 56; a higher score indicates a higher level of anxiety.	24 weeks
Change in stress symptoms	Change from baseline to week 24 in Depression Anxiety Stress Scales (DASS-42) Stress Subscale score. Scores range from 0-42; a higher score indicates a higher level of stress.	24 weeks
Change in cognitive performance	Change from baseline to week 24 in Matrics Consensus Cognitive Battery (MCCB) Total Score. Scores range from 0.00% - 100.00%; a higher score indicates higher cognition.	24 weeks
Change in Global Functioning Scale (GFS) - Social and Role total score	Change from baseline to week 24 in Global Functioning Scale (GFS) - Social and Role total score. Scores range from 6-60; a lower score indicates worse social and role functioning.	24 weeks
Change in blood NAD/NADH+ ratio	Change from baseline to week 24 in blood NAD/NADH+ ratio.	24 weeks
Change in blood GSH/GSSH ratio	Change from baseline to week 24 in blood GSH/GSSH ratio.	24 weeks
Change in growth differentiation factor 15 (GDF15)	Change from baseline to week 24 in blood and saliva GDF15 levels.	24 weeks
Change in cell-free mitochondrial DNA (cf-mtDNA)	Change from baseline to week 24 in blood and saliva cf-mtDNA levels.	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in World Health Organization Disability Assessment Schedule (WHODAS) score	Change from baseline to week 24 in World Health Organization Disability Assessment Schedule (WHODAS) scale. Scores range from 0-144. A higher score indicates greater dysfunction and disability in major life domains.	24 weeks
Change in World Health Organization Quality of Life (WHOQOL) score	Change from baseline to week 24 in World Health Organization Quality of Life (WHOQOL) scale. Scores range from 1-130. A lower score indicates lower perceived quality of life.	24 weeks
Change in Extrapyramidal Symptom Rating Scale (ESRS) total score	Change from baseline to week 24 in Extrapyramidal Symptom Rating Scale (ESRS) total score. Scores range from 0-102; a higher score indicates more severe symptoms.	24 weeks
Change in Pittsburgh Sleep Quality Index (PSQI) total score	Change from baseline to week 24 in Pittsburgh Sleep Quality Index (PSQI) total score. Scores range from 0-21; a higher score indicates worse sleep quality.	24 weeks
Change in resting-state fMRI	Change within network positive correlations and between network negative correlations from baseline to week 24.	24 weeks
Change in gray matter volume	Change in the gray matter volumes (cubic millimeters) of the frontal, parietal and temporal lobes as defined by Freesurfer's Desikan-Killiany Brain Atlas from baseline to week 24.	24 weeks
Change in cortical surface area	Change in the cortical surface area (millimeters squared) of the frontal, parietal and temporal lobes as defined by Freesurfer's Desikan-Killiany Brain Atlas from baseline to week 24.	24 weeks
Change in white matter fractional anisotropy (FA)	Change in fractional anisotropy (FA), a scalar measure of diffusivity, of water in the brain assessed by DTI at 3T from baseline to week 24. FA values range from 0 (isotropic, meaning diffusion is equally restricted in 3D space) to 1 (anisotrophic, meaning that diffusion is completely restricted to a single direction).	24 weeks

Collaborators and Investigators

• Sponsor: Mclean Hospital
• Collaborators: Baszucki Family Foundation
• Investigators: Principal Investigator: Virginie-Anne Chouinard, MD, McLean Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2024
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: August 14, 2024
• First Submitted That Met QC Criteria: August 14, 2024
• First Posted (Actual): August 16, 2024

Study Record Updates

• Last Update Posted (Actual): April 17, 2025
• Last Update Submitted That Met QC Criteria: April 14, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Insulin resistance; Bipolar disorder; Schizoaffective disorder; Ketogenic diet; First episode psychosis; Magnetic resonance spectroscopy (MRS); Brain energy metabolism; Redox; Creatine kinase; Keto
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Psychotic Disorders; Mental Disorders
• Other Study ID Numbers: 2023P002849-2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No