Bipolar I Disorder, Psychosis, Schizoaffective Disorder
Conditions
Keywords
First episode psychosis, Ketogenic diet, Keto, Brain energy metabolism, Insulin resistance, Schizoaffective disorder, Bipolar disorder, Magnetic resonance spectroscopy (MRS), Redox, Creatine kinase
Brief summary
This is a 12-week open-label extension study for participants completing study NCT06221852.
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.
Interventions
OTHERKetogenic 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.
Sponsors
Mclean Hospital
Baszucki Family Foundation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All participants will have completed the 12-week randomized controlled trial (NCT06221852), and will follow the ketogenic diet in this open label extension.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in brain redox nicotinamide adenine dinucleotide metabolites ratio (NAD+/NADH) | 24 weeks | Change from baseline to week 24 in NAD+/NADH as measured by in vivo phosphorus magnetic resonance spectroscopy (31P-MRS). |
| Change in brain creatine kinase forward reaction rate (kf) | 24 weeks | Change from baseline to week 24 in creatine kinase forward reaction rate (kf) as measured by 31P magnetization transfer (MT) MRS. |
| Change in insulin resistance | 24 weeks | 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. |
| Change in psychotic symptoms | 24 weeks | 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. |
| Change in depressive symptoms | 24 weeks | 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. |
| Change in mania symptoms | 24 weeks | 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. |
| Change in Clinical Global Impression (CGI) Scale | 24 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in body weight | 24 weeks | Change from baseline to week 24 in participant body weight in kilograms, as measured using a standing scale. |
| Change in glycated hemoglobin (Hemoglobin A1c) level | 24 weeks | Change from baseline to week 24 in fasting Hemoglobin A1c level. |
| Change in triglyceride levels | 24 weeks | Change from baseline to week 24 in fasting triglyceride levels. |
| Change in low-density lipoprotein (LDL) levels | 24 weeks | Change from baseline to week 24 in fasting LDL levels |
| Change in high-density lipoprotein (HDL) levels | 24 weeks | Change from baseline to week 24 in fasting HDL levels |
| Change in high-sensitivity C-reactive protein (hs-CRP) levels | 24 weeks | Change from baseline to week 24 in fasting hs-CRP levels. |
| Change in brain gamma-aminobutyric acid (GABA) concentration | 24 weeks | Change from baseline to week 24 in GABA concentration measured by proton magnetic resonance spectroscopy. |
| Change in brain glutamate metabolite concentration | 24 weeks | Change from baseline to week 24 in glutamate metabolite concentration measured by proton magnetic resonance spectroscopy. |
| Change in brain glutathione (GSH) | 24 weeks | Change from baseline to week 24 in brain GSH measured by proton magnetic resonance spectroscopy. |
| Change in brain Phosphocreatine (PCr) | 24 weeks | Changes from baseline to week 24 in PCr concentration as measured by in vivo 31P-MRS. |
| Change in brain pH | 24 weeks | Change from baseline to week 24 in pH as measured by in vivo 31P MRS |
| Change in brain inorganic phosphate concentration | 24 weeks | Change from baseline to week 24 in inorganic phosphate (Pi) concentration as measured by in vivo 31P MRS. |
| Change in adverse events | 24 weeks | Change from baseline to week 24 in adverse events. |
| Change in anxiety symptoms | 24 weeks | 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. |
| Change in stress symptoms | 24 weeks | 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. |
| Change in cognitive performance | 24 weeks | 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. |
| Change in Global Functioning Scale (GFS) - Social and Role total score | 24 weeks | 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. |
| Change in blood NAD/NADH+ ratio | 24 weeks | Change from baseline to week 24 in blood NAD/NADH+ ratio. |
| Change in blood GSH/GSSH ratio | 24 weeks | Change from baseline to week 24 in blood GSH/GSSH ratio. |
| Change in growth differentiation factor 15 (GDF15) | 24 weeks | Change from baseline to week 24 in blood and saliva GDF15 levels. |
| Change in cell-free mitochondrial DNA (cf-mtDNA) | 24 weeks | Change from baseline to week 24 in blood and saliva cf-mtDNA levels. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORVirginie-Anne Chouinard, MD
Mclean Hospital
Outcome results
None listed