Open Label Extension Study of NCT06221852
NCT Number: NCT06558201
Status: ENROLLING_BY_INVITATION
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Bipolar I Disorder|Schizoaffective Disorder|Psychosis
Interventions: OTHER: Ketogenic diet
Sponsor: Mclean Hospital
Collaborators: Baszucki Family Foundation
Sex: ALL
Age: ADULT
Enrollment: 50
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-16
Completion Date: 2027-12-30
Locations: McLean Hospital, Belmont, Massachusetts, 02487, United States

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

Primary Outcome Measures: 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: 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: 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