Impact of a Ketogenic Diet on Metabolic and Psychiatric Health in Patients With Bipolar or Schizophrenia Illness

Study Overview
=================
Brief Summary
-----------------
To initiate a low-carbohydrate, high-fat (LCHF) or ketogenic dietary (KD) intervention among a cohort of outpatients with either schizophrenia or bipolar illness who also have metabolic abnormalities, overweight/obesity, and/or are currently taking psychotropic medications experiencing metabolic side effects.

Detailed Description
-----------------
Adults with mental illness represent a high-risk, marginalized group in the current metabolic and obesity epidemic. Among US adults with severe mental illness, metabolic syndrome are highly prevalent conditions having severe consequences, with patients estimated to die on average 25 years earlier than the general population largely of premature cardiovascular disease. Many psychiatric medications, particularly neuroleptics and mood stabilizers, may, in addition, contribute to metabolic side effects and weight gain. Low-carbohydrate high-fat (LCHF) or ketogenic diets (KD) have been shown to reduce cardiovascular risk in those with insulin resistance. Recent findings support the idea that bipolar disorder, along with other psychiatric diseases schizophrenia, may have roots of metabolic dysfunction: cerebral glucose hypometabolism, oxidative stress, as well as mitochondrial and neurotransmitter dysfunction which has downstream effects on synapse connections. A KD diet provides alternative fuel to the brain aside from glucose and is believed to contain beneficial neuroprotective effects, including stabilization of brain networks, reduction of inflammation and oxidative stress. The purpose of this study is to evaluate both the metabolic and psychiatric outcomes with a KD diet in this psychiatric population.

Official Title
-----------------
Impact of A Low-Carbohydrate, High-Fat, Ketogenic Diet on Obesity, Metabolic Abnormalities and Psychiatric Symptoms in Patients With Bipolar or Schizophrenia Illness: A Pilot Trial

Conditions
-----------------
Obesity, Ketogenic Dieting, Metabolic Syndrome, Bipolar Disorder, Schizophrenia, Weight Gain, Psychotropic Agents Causing Adverse Effects in Therapeutic Use, Brain Metabolic Disorder

Intervention / Treatment
-----------------
* Other: LCHF, Ketogenic Diet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18-75 years old Meet DSM V criteria for schizophrenia or bipolar disorder, any subtype, for > 1 year and clinically stable (with no hospitalization for past 3 months) Currently taking psychotropic medication and gained at least 5% weight since starting medication or have a BMI greater than or equal to 26 kg/m2 or presence of at least one metabolic abnormality (hypertriglyceridemia, insulin resistance, dyslipidemia, impaired glucose tolerance) Willing to consent to all study procedures and attend follow-up appointments and motivated to follow the dietary program. Sufficient control over their food intake to adhere to study diets. Willingness to regularly monitor blood pressure, glucose, dietary intake, and body weight over the 4-month trial Exclusion Criteria: Any subject pregnant or nursing Comorbidity of developmental delay Active substance abuse with illicit drugs or alcohol In a current severe mood or psychotic state when entering the study that would prohibit compliance with study visits or dietary program. Anyone who has been hospitalized or taken clozapine over the past 3 months Inability to complete baseline measurements Severe renal or hepatic insufficiency Cardiovascular dysfunction, including diagnosis of: Congestive heart failure Angina Arrhythmias Cardiomyopathy Valvular heart disease Any other medical condition that may make either diet dangerous as determined by the study medical team (e.g. anorexia nervosa)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketogenic Diet 16 Week Group<br>Patients follow ketogenic diet for 16 weeks, with monitoring of physical and psychological health and coaching support | Other: LCHF, Ketogenic Diet<br>* Low Carbohydrate, Moderate Protein, High Fat Ketogenic Dietary Intervention 16 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in heart rate from baseline | Heart rate recorded at 9 visits during study | Baseline, 16 weeks | 
| Change in blood pressure from baseline | Blood pressure recorded at 9 visits during study | Baseline, 16 weeks | 
| Change in weight from baseline | Weight recorded at 9 visits during study | Baseline, 16 weeks | 
| Change in waist circumference from baseline | waist circumference measured at 9 visits during study | Baseline, 16 weeks | 
| Change in visceral fat mass from baseline | Body composition (SECA) recorded at 5 visits during study | Baseline, 16 weeks | 
| Change in body fat mass from baseline | Body composition (SECA) recorded at 5 visits during study | Baseline, 16 weeks | 
| Percent Change in Hemoglobin A1c from baseline | Hemoglobin A1c recorded at initial and final visits | Baseline, 16 weeks | 
| Change in insulin resistance measure (HOMA-IR) from baseline | HOMA-IR measured at initial and final visits | Baseline, 16 weeks | 
| Change in inflammatory marker (hsCRP) from baseline | hsCRP measured at initial and final visits | Baseline, 16 weeks | 
| Change in lipid profile TG (triglycerides) from baseline | Lipid profile TG measured at initial and final visits | Baseline, 16 weeks | 
| Change in lipid profile small LDL (small dense LDL) from baseline | Lipid profile small LDL measured at initial and final visits | Baseline, 16 weeks | 
| Change in lipid profile (HDL) from baseline | Lipid profile HDL measured at initial and final visits | Baseline,16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psychiatric Indices - Mood | Change in Mood Qualitative Score (Clinical Mood Monitoring) from baseline | Baseline, 16 weeks | 
| Psychiatric Indices- Clinical Global Impression | Change in Clinical Global Impression Scales (CGI) from baseline 1-7 scale. 1= not at all ill, 7= among the most extremely ill patients) | Baseline, 16 weeks | 
| Generalized Anxiety Disorder - GAD-7 Anxiety | Change in Generalized Anxiety Symptom (GAD-7) scale from baseline. 0-15+ scale. (0= no anxiety, 15+= severe anxiety) | Baseline, 16 weeks | 
| Patient Health Questionnaire - PHQ-9 Depression | Change in Patient Health Questionnaire (PHQ-9) from baseline. Score range 0-27 (0= no depression, 27= severe depression) | Baseline, 16 weeks | 
| Psychiatric Indices- Global Assessment of Functioning | Change in Global Assessment of Functioning (GAF) Scale from baseline. 1-100 scale (1= persistent danger of hurting self or others, 100= superior functioning) | Baseline, 16 weeks | 
| Psychiatric Indices- Quality of Life | Change in Manchester Quality of Life Scale (MANSA) from baseline. Range 12-84 (each of 12 outcomes rated from 1= could not be worse to 7= could not be better; <4= dissatisfied with QoL, >4= satisfied with QoL) | Baseline, 16 weeks | 
| Psychiatric Indices- BPRS | Change in Brief Psychiatric Rating Scale (BPRS) from baseline. Score range 18-126. (For each of 18 symptoms, 1=symptom not present, 7= extremely severe) | Baseline, 16 weeks | 
| Pittsburgh Sleep Quality Index - PSQI | Change in Pittsburgh Sleep Quality Index from baseline. 0-21 scale (<5=good sleeper; 5+= meaningfully disturbed sleep or poor sleeper) | Baseline, 16 weeks |