Ketogenic and Nutritional Interventions for First Episode Bipolar Disorder

Mclean Hospital50 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Bipolar I Disorder Psychosis Schizoaffective Disorder

Interventions

Ketogenic dietOTHER

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 AmericansOTHER

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).

Eligibility

Sex: ALLMin age: 18 YearsMax age: 45 Years

Medical Language ↔ Plain English

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

Locations (1)

McLean Hospital

Belmont, Massachusetts, United States

RECRUITING

Outcomes

Primary Outcomes

Change in brain redox nicotinamide adenine dinucleotide metabolites ratio (NAD+/NADH)

Change from baseline to week 12 in NAD+/NADH as measured by in vivo phosphorus magnetic resonance spectroscopy (31P-MRS).

Time frame: 12 weeks

Change in brain creatine kinase forward reaction rate (kf)

Change from baseline to week 12 in creatine kinase forward reaction rate (kf) as measured by 31P magnetization transfer (MT) MRS.

Time frame: 12 weeks

Change in insulin resistance

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.

Time frame: 12 weeks

Change in psychotic symptoms

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.

Time frame: 12 weeks

Change in depressive symptoms

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.

Time frame: 12 weeks

Change in mania symptoms

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.

Time frame: 12 weeks

Change in Clinical Global Impression (CGI) Scale

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.

Central Contacts

Jacey Anderson, B.A.

CONTACT

617-855-3988 janderson75@mclean.harvard.edu

Virginie-Anne Chouinard, MD

CONTACT

vchouinard@mclean.harvard.edu

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

Change in body weight

Change from baseline to week 12 in participant body weight in kilograms, as measured using a standing scale.

Time frame: 12 weeks

Change in glycated hemoglobin (Hemoglobin A1c) level

Change from baseline to week 12 in fasting Hemoglobin A1c level.

Time frame: 12 weeks

Change in triglyceride levels

Change from baseline to week 12 in fasting triglyceride levels.

Time frame: 12 weeks

Change in low-density lipoprotein (LDL) levels

Change from baseline to week 12 in fasting LDL levels.

Time frame: 12 weeks

Change in high-density lipoprotein (HDL) levels

Change from baseline to week 12 in fasting HDL levels.

Time frame: 12 weeks

Change in high-sensitivity C-reactive protein (hs-CRP) levels

Change from baseline to week 12 in fasting hs-CRP levels.

Time frame: 12 weeks

Change in brain gamma-aminobutyric acid (GABA) concentration

Change from baseline to week 12 in GABA concentration measured by proton magnetic resonance spectroscopy.

Time frame: 12 weeks

Change in brain glutamate metabolite concentration

Change from baseline to week 12 in glutamate metabolite concentration measured by proton magnetic resonance spectroscopy.

Time frame: 12 weeks

Change in brain glutathione (GSH)

Change from baseline to week 12 in brain GSH measured by proton magnetic resonance spectroscopy.

Time frame: 12 weeks

Change in brain Phosphocreatine (PCr)

Changes from baseline to week 12 in PCr concentration as measured by in vivo 31P-MRS.

Time frame: 12 weeks

Change in brain pH

Change from baseline to week 12 in pH as measured by in vivo 31P MRS.

Time frame: 12 weeks

Change in brain inorganic phosphate concentration

Change from baseline to week 12 in inorganic phosphate (Pi) concentration as measured by in vivo 31P MRS.

Time frame: 12 weeks

Change in adverse events

Change from baseline to week 12 from baseline to week 12 in adverse events.

Time frame: 12 weeks

Change in anxiety symptoms

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.

Time frame: 12 weeks

Change in stress symptoms

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.

Time frame: 12 weeks

Change in cognitive performance

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.

Time frame: 12 weeks

Change in Global Functioning Scale (GFS) - Social and Role total score

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.

Time frame: 12 weeks

Change in cell-free mitochondrial DNA (cf-mtDNA)

Change from baseline to week 12 in blood and saliva cf-mtDNA levels.

Time frame: 12 weeks

Change in growth differentiation factor 15 (GDF15)

Change from baseline to week 12 in blood and saliva GDF15 levels.

Time frame: 12 weeks

Change in blood NAD/NADH+ ratio

Change from baseline to week 12 in blood NAD/NADH+ ratio.

Time frame: 12 weeks

Change in blood GSH/GSSH ratio

Change from baseline to week 12 in blood GSH/GSSH ratio.

Time frame: 12 weeks