Ketogenic and Nutritional Interventions for First Episode Bipolar Disorder

Schizoaffective Disorder Clinical Trial

Official title:

A Randomized Controlled Clinical Trial of Ketogenic and Nutritional Interventions for Brain Energy Metabolism and Psychiatric Symptoms in First Episode Bipolar Disorder.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06221852
• Other study ID #: 2023P002849
• Status: Recruiting
• Phase: N/A
• Start date: March 12, 2024
• Est. completion date: December 30, 2027

Study information

• Verified date: April 2024
• Source: Mclean Hospital
• Contact: Jacey Anderson, B.A.
• Phone: 617-855-3988
• Email: janderson75[@]mclean.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 30, 2027
• Est. primary completion date: September 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Bipolar Disorder
• Bipolar I Disorder
• Mental Disorders
• Psychosis
• Psychotic Disorders
• Schizoaffective Disorder

Intervention

Other:
• Ketogenic 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
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).

Locations

Country	Name	City	State
United States	McLean Hospital	Belmont	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Mclean Hospital	Baszucki Family Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in World Health Organization Disability Assessment Schedule (WHODAS) score	Change from baseline to week 12 in World Health Organization Disability Assessment Schedule (WHODAS) scale. Scores range from 0-144. A higher score indicates greater dysfunction and disability in major life domains.	12 weeks
Other	Change in World Health Organization Quality of Life (WHOQOL) score	Change from baseline to week 12 in World Health Organization Quality of Life (WHOQOL) scale. Scores range from 1-130. A lower score indicates lower perceived quality of life.	12 weeks
Other	Change in Extrapyramidal Symptom Rating Scale (ESRS) total score	Change from baseline to week 12 in Extrapyramidal Symptom Rating Scale (ESRS) total score. Scores range from 0-102; a higher score indicates more severe symptoms.	12 weeks
Other	Change in Pittsburgh Sleep Quality Index (PSQI) total score	Change from baseline to week 12 in Pittsburgh Sleep Quality Index (PSQI) total score. Scores range from 0-21; a higher score indicates worse sleep quality.	12 weeks
Primary	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).	12 weeks
Primary	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.	12 weeks
Primary	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.	12 weeks
Primary	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.	12 weeks
Primary	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.	12 weeks
Primary	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.	12 weeks
Primary	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.	12 weeks
Secondary	Change in body weight	Change from baseline to week 12 in participant body weight in kilograms, as measured using a standing scale.	12 weeks
Secondary	Change in glycated hemoglobin (Hemoglobin A1c) level	Change from baseline to week 12 in fasting Hemoglobin A1c level.	12 weeks
Secondary	Change in triglyceride levels	Change from baseline to week 12 in fasting triglyceride levels.	12 weeks
Secondary	Change in low-density lipoprotein (LDL) levels	Change from baseline to week 12 in fasting LDL levels.	12 weeks
Secondary	Change in high-density lipoprotein (HDL) levels	Change from baseline to week 12 in fasting HDL levels.	12 weeks
Secondary	Change in high-sensitivity C-reactive protein (hs-CRP) levels	Change from baseline to week 12 in fasting hs-CRP levels.	12 weeks
Secondary	Change in brain gamma-aminobutyric acid (GABA) concentration	Change from baseline to week 12 in GABA concentration measured by proton magnetic resonance spectroscopy.	12 weeks
Secondary	Change in brain glutamate metabolite concentration	Change from baseline to week 12 in glutamate metabolite concentration measured by proton magnetic resonance spectroscopy.	12 weeks
Secondary	Change in brain glutathione (GSH)	Change from baseline to week 12 in brain GSH measured by proton magnetic resonance spectroscopy.	12 weeks
Secondary	Change in brain Phosphocreatine (PCr)	Changes from baseline to week 12 in PCr concentration as measured by in vivo 31P-MRS.	12 weeks
Secondary	Change in brain pH	Change from baseline to week 12 in pH as measured by in vivo 31P MRS.	12 weeks
Secondary	Change in brain inorganic phosphate concentration	Change from baseline to week 12 in inorganic phosphate (Pi) concentration as measured by in vivo 31P MRS.	12 weeks
Secondary	Change in adverse events	Change from baseline to week 12 from baseline to week 12 in adverse events.	12 weeks
Secondary	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.	12 weeks
Secondary	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.	12 weeks
Secondary	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.	12 weeks
Secondary	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.	12 weeks