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 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.
Detailed description
Several lines of evidence show energy metabolism and redox dysregulation in bipolar disorder and psychotic disorders. Ketogenic interventions targeting energy metabolism are promising therapeutic approaches to improve mood and psychosis in bipolar disorder and other psychotic disorders. Early intervention is also critical to helping people achieve their goals for recovery after a first episode. Investigators aim to use multimodal imaging and metabolic measures to study the effects of a ketogenic diet intervention on energy metabolism and psychiatric symptoms in individuals with first episode bipolar disorder and schizoaffective disorder. This 12-week randomized controlled trial will assess the benefits of a ketogenic diet in combination with treatment as usual compared to a standard diet. Investigators will measure the effects of nutritional ketosis on brain redox and energy metabolism and other neurometabolic markers using magnetic resonance spectroscopy. Furthermore, investigators will measure the effects of the ketogenic diet on mood and psychotic symptoms and metabolic measures such as insulin resistance.
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.
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).
Sponsors
Mclean Hospital
Baszucki Family Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 resistance | 12 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 symptoms | 12 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 symptoms | 12 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 symptoms | 12 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) Scale | 12 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in body weight | 12 weeks | Change from baseline to week 12 in participant body weight in kilograms, as measured using a standing scale. |
| Change in glycated hemoglobin (Hemoglobin A1c) level | 12 weeks | Change from baseline to week 12 in fasting Hemoglobin A1c level. |
| Change in triglyceride levels | 12 weeks | Change from baseline to week 12 in fasting triglyceride levels. |
| Change in low-density lipoprotein (LDL) levels | 12 weeks | Change from baseline to week 12 in fasting LDL levels. |
| Change in high-density lipoprotein (HDL) levels | 12 weeks | Change from baseline to week 12 in fasting HDL levels. |
| Change in high-sensitivity C-reactive protein (hs-CRP) levels | 12 weeks | Change from baseline to week 12 in fasting hs-CRP levels. |
| Change in brain gamma-aminobutyric acid (GABA) concentration | 12 weeks | Change from baseline to week 12 in GABA concentration measured by proton magnetic resonance spectroscopy. |
| Change in brain glutamate metabolite concentration | 12 weeks | Change from baseline to week 12 in glutamate metabolite concentration measured by proton magnetic resonance spectroscopy. |
| Change in brain glutathione (GSH) | 12 weeks | Change from baseline to week 12 in brain GSH measured by proton magnetic resonance spectroscopy. |
| Change in brain Phosphocreatine (PCr) | 12 weeks | Changes from baseline to week 12 in PCr concentration as measured by in vivo 31P-MRS. |
| Change in brain pH | 12 weeks | Change from baseline to week 12 in pH as measured by in vivo 31P MRS. |
| Change in brain inorganic phosphate concentration | 12 weeks | Change from baseline to week 12 in inorganic phosphate (Pi) concentration as measured by in vivo 31P MRS. |
| Change in adverse events | 12 weeks | Change from baseline to week 12 from baseline to week 12 in adverse events. |
| Change in anxiety symptoms | 12 weeks | Change from baseline to week 12 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 | 12 weeks | Change from baseline to week 12 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 | 12 weeks | Change from baseline to week 12 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 | 12 weeks | Change from baseline to week 12 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 cell-free mitochondrial DNA (cf-mtDNA) | 12 weeks | Change from baseline to week 12 in blood and saliva cf-mtDNA levels. |
| Change in growth differentiation factor 15 (GDF15) | 12 weeks | Change from baseline to week 12 in blood and saliva GDF15 levels. |
| Change in blood NAD/NADH+ ratio | 12 weeks | Change from baseline to week 12 in blood NAD/NADH+ ratio. |
| Change in blood GSH/GSSH ratio | 12 weeks | Change from baseline to week 12 in blood GSH/GSSH ratio. |
Countries
United States
Contacts
CONTACTKaitlin Shannon, B.A.
CONTACTVirginie-Anne Chouinard, MD
PRINCIPAL_INVESTIGATORVirginie-Anne Chouinard, MD
Mclean Hospital
Outcome results
None listed