Ketogenic and Nutritional Interventions for First Episode Bipolar Disorder
- Conditions
- Schizoaffective DisorderPsychosisBipolar I Disorder
- Interventions
- Other: Ketogenic dietOther: Dietary Guidelines for Americans
- Registration Number
- NCT06221852
- Lead Sponsor
- Mclean Hospital
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 50
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ketogenic diet arm Ketogenic diet Eligible participants assigned to the ketogenic diet arm 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 weekly and as needed diet counseling from a registered dietician. Participants will be asked to monitor and report their blood ketone levels each day via a finger-prick device provided by the study team. Participants have the ability to opt into an optional open label phase where they can continue on the ketogenic diet with the daily finger pricks for another 12 weeks after the 12-week main study. Dietary Guidelines for Americans arm Dietary Guidelines for Americans Eligible participants assigned to the Dietary Guidelines for Americans (DGA) arm will adhere to the Dietary Guidelines for Americans in addition to any ongoing medications (e.g., mood stabilizers and/or second-generation antipsychotics). Participants will receive weekly and as needed diet counseling from a registered dietician. Participants will be asked to monitor and report their blood ketone levels each day via a finger-prick device provided by the study team. Participants have the ability to opt into an optional open label phase where they can switch to the ketogenic diet with the daily finger pricks for 12 weeks after the 12-week main study.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Change in blood NAD/NADH+ ratio 12 weeks Change from baseline to week 12 in blood NAD/NADH+ ratio.
Change in glycated hemoglobin (Hemoglobin A1c) level 12 weeks Change from baseline to week 12 in fasting Hemoglobin A1c level.
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 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 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 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 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 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 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 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 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 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 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 blood GSH/GSSH ratio 12 weeks Change from baseline to week 12 in blood GSH/GSSH ratio.
Trial Locations
- Locations (1)
McLean Hospital
šŗšøBelmont, Massachusetts, United States