A Randomized Controlled Clinical Trial of Ketogenic and Nutritional Interventions for Brain Energy Metabolism and Psychiatric Symptoms in First Episode Bipolar Disorder.
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Bipolar I Disorder
- Sponsor
- Mclean Hospital
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Change in brain redox nicotinamide adenine dinucleotide metabolites ratio (NAD+/NADH)
- Status
- Recruiting
- Last Updated
- 5 months ago
Overview
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.
Investigators
Virginie-Anne Chouinard, MD
Psychiatrist
Mclean Hospital
Eligibility Criteria
Inclusion Criteria
- •Between the ages of 18 and
- •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
Outcomes
Primary Outcomes
Change in brain redox nicotinamide adenine dinucleotide metabolites ratio (NAD+/NADH)
Time Frame: 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)
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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 Outcomes
- Change in glycated hemoglobin (Hemoglobin A1c) level(12 weeks)
- Change in body weight(12 weeks)
- Change in triglyceride levels(12 weeks)
- Change in low-density lipoprotein (LDL) levels(12 weeks)
- Change in brain gamma-aminobutyric acid (GABA) concentration(12 weeks)
- Change in high-density lipoprotein (HDL) levels(12 weeks)
- Change in high-sensitivity C-reactive protein (hs-CRP) levels(12 weeks)
- Change in brain glutamate metabolite concentration(12 weeks)
- Change in brain glutathione (GSH)(12 weeks)
- Change in brain Phosphocreatine (PCr)(12 weeks)
- Change in brain pH(12 weeks)
- Change in adverse events(12 weeks)
- Change in anxiety symptoms(12 weeks)
- Change in cell-free mitochondrial DNA (cf-mtDNA)(12 weeks)
- Change in growth differentiation factor 15 (GDF15)(12 weeks)
- Change in blood NAD/NADH+ ratio(12 weeks)
- Change in brain inorganic phosphate concentration(12 weeks)
- Change in stress symptoms(12 weeks)
- Change in Global Functioning Scale (GFS) - Social and Role total score(12 weeks)
- Change in cognitive performance(12 weeks)
- Change in blood GSH/GSSH ratio(12 weeks)