Clinical trial NCT06221852: Ketogenic and Nutritional Interventions for First Episode Bipolar Disorder
Official title: A Randomized Controlled Clinical Trial of Ketogenic and Nutritional Interventions for Brain Energy Metabolism and Psychiatric Symptoms in First Episode Bipolar Disorder.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Bipolar I Disorder
Psychosis
Schizoaffective Disorder
Keywords: First episode psychosis
Ketogenic Diet
Keto
Brain energy metabolism
Insulin resistance
Schizoaffective Disorder
Bipolar Disorder
Magnetic resonance spectroscopy (MRS)
Redox
Creatine kinase
Lead sponsor: Mclean Hospital
Sponsor class: OTHER
Collaborators: name: Baszucki Family Foundation
First posted: 2024-01-24
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in brain redox nicotinamide adenine dinucleotide metabolites ratio (NAD+/NADH)
timeFrame: 12 weeks
measure: Change in brain creatine kinase forward reaction rate (kf)
timeFrame: 12 weeks
measure: Change in insulin resistance
timeFrame: 12 weeks
measure: Change in psychotic symptoms
timeFrame: 12 weeks
measure: Change in depressive symptoms
timeFrame: 12 weeks
measure: Change in mania symptoms
timeFrame: 12 weeks
measure: Change in Clinical Global Impression (CGI) Scale
timeFrame: 12 weeks
Secondary outcomes:
measure: Change in body weight
timeFrame: 12 weeks
measure: Change in glycated hemoglobin (Hemoglobin A1c) level
timeFrame: 12 weeks
measure: Change in triglyceride levels
timeFrame: 12 weeks
measure: Change in low-density lipoprotein (LDL) levels
timeFrame: 12 weeks
measure: Change in high-density lipoprotein (HDL) levels
timeFrame: 12 weeks
measure: Change in high-sensitivity C-reactive protein (hs-CRP) levels
timeFrame: 12 weeks
measure: Change in brain gamma-aminobutyric acid (GABA) concentration
timeFrame: 12 weeks
measure: Change in brain glutamate metabolite concentration
timeFrame: 12 weeks
measure: Change in brain glutathione (GSH)
timeFrame: 12 weeks
measure: Change in brain Phosphocreatine (PCr)
timeFrame: 12 weeks
measure: Change in brain pH
timeFrame: 12 weeks
measure: Change in brain inorganic phosphate concentration
timeFrame: 12 weeks
measure: Change in adverse events
timeFrame: 12 weeks
measure: Change in anxiety symptoms
timeFrame: 12 weeks
measure: Change in stress symptoms
timeFrame: 12 weeks
measure: Change in cognitive performance
timeFrame: 12 weeks
measure: Change in Global Functioning Scale (GFS) - Social and Role total score
timeFrame: 12 weeks
measure: Change in cell-free mitochondrial DNA (cf-mtDNA)
timeFrame: 12 weeks
measure: Change in growth differentiation factor 15 (GDF15)
timeFrame: 12 weeks
measure: Change in blood NAD/NADH+ ratio
timeFrame: 12 weeks
measure: Change in blood GSH/GSSH ratio
timeFrame: 12 weeks
Other outcomes:
measure: Change in World Health Organization Disability Assessment Schedule (WHODAS) score
timeFrame: 12 weeks
measure: Change in World Health Organization Quality of Life (WHOQOL) score
timeFrame: 12 weeks
measure: Change in Extrapyramidal Symptom Rating Scale (ESRS) total score
timeFrame: 12 weeks
measure: Change in Pittsburgh Sleep Quality Index (PSQI) total score
timeFrame: 12 weeks
measure: Change in resting-state fMRI
timeFrame: 12 weeks
measure: Change in gray matter volume
timeFrame: 12 weeks
measure: Change in cortical surface area
timeFrame: 12 weeks
measure: Change in white matter fractional anisotropy (FA)
timeFrame: 12 weeks
Locations:
city: Belmont
country: United States
facility: McLean Hospital
state: Massachusetts
Study officials:
affiliation: Mclean Hospital
name: Virginie-Anne Chouinard, MD
role: PRINCIPAL_INVESTIGATOR
References: