Clinical trial NCT03935854: Impact of a Ketogenic Diet on Metabolic and Psychiatric Health in Patients With Bipolar or Schizophrenia Illness
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Ketogenic Dieting
Metabolic Syndrome
Bipolar Disorder
Schizophrenia
Weight Gain
Psychotropic Agents Causing Adverse Effects in Therapeutic Use
Brain Metabolic Disorder
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2019-05-02
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Age 18-75 years old
2. Meet DSM V criteria for schizophrenia or bipolar disorder, any subtype, for \> 1 year and clinically stable (with no hospitalization for past 3 months)
3. 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)
4. Willing to consent to all study procedures and attend follow-up appointments and motivated to follow the dietary program.
5. Sufficient control over their food intake to adhere to study diets.
6. Willingness to regularly monitor blood pressure, glucose, dietary intake, and body weight over the 4-month trial

Exclusion Criteria:

1. Any subject pregnant or nursing
2. Comorbidity of developmental delay
3. Active substance abuse with illicit drugs or alcohol
4. In a current severe mood or psychotic state when entering the study that would prohibit compliance with study visits or dietary program.
5. Anyone who has been hospitalized or taken clozapine over the past 3 months
6. Inability to complete baseline measurements
7. Severe renal or hepatic insufficiency
8. Cardiovascular dysfunction, including diagnosis of:

   1. Congestive heart failure
   2. Angina
   3. Arrhythmias
   4. Cardiomyopathy
   5. Valvular heart disease
9. Any other medical condition that may make either diet dangerous as determined by the study medical team (e.g. anorexia nervosa)

Primary outcomes:
measure: Change in heart rate from baseline
timeFrame: Baseline, 16 weeks
measure: Change in blood pressure from baseline
timeFrame: Baseline, 16 weeks
measure: Change in weight from baseline
timeFrame: Baseline, 16 weeks
measure: Change in waist circumference from baseline
timeFrame: Baseline, 16 weeks
measure: Change in visceral fat mass from baseline
timeFrame: Baseline, 16 weeks
measure: Change in body fat mass from baseline
timeFrame: Baseline, 16 weeks
measure: Percent Change in Hemoglobin A1c from baseline
timeFrame: Baseline, 16 weeks
measure: Change in insulin resistance measure (HOMA-IR) from baseline
timeFrame: Baseline, 16 weeks
measure: Change in inflammatory marker (hsCRP) from baseline
timeFrame: Baseline, 16 weeks
measure: Change in lipid profile TG (triglycerides) from baseline
timeFrame: Baseline, 16 weeks
measure: Change in lipid profile small LDL (small dense LDL) from baseline
timeFrame: Baseline, 16 weeks
measure: Change in lipid profile (HDL) from baseline
timeFrame: Baseline,16 weeks
Secondary outcomes:
measure: Psychiatric Indices - Mood
timeFrame: Baseline, 16 weeks
measure: Psychiatric Indices- Clinical Global Impression
timeFrame: Baseline, 16 weeks
measure: Generalized Anxiety Disorder - GAD-7 Anxiety
timeFrame: Baseline, 16 weeks
measure: Patient Health Questionnaire - PHQ-9 Depression
timeFrame: Baseline, 16 weeks
measure: Psychiatric Indices- Global Assessment of Functioning
timeFrame: Baseline, 16 weeks
measure: Psychiatric Indices- Quality of Life
timeFrame: Baseline, 16 weeks
measure: Psychiatric Indices- BPRS
timeFrame: Baseline, 16 weeks
measure: Pittsburgh Sleep Quality Index - PSQI
timeFrame: Baseline, 16 weeks
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University Department of Psychiatry & Behavioral Sciences
state: California
Study officials:
affiliation: Stanford University
name: Shebani Sethi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sethi S, Sinha A, Gearhardt AN. Low carbohydrate ketogenic therapy as a metabolic treatment for binge eating and ultraprocessed food addiction. Curr Opin Endocrinol Diabetes Obes. 2020 Oct;27(5):275-282. doi: 10.1097/MED.0000000000000571.
citation: Carmen M, Safer DL, Saslow LR, Kalayjian T, Mason AE, Westman EC, Sethi S. Treating binge eating and food addiction symptoms with low-carbohydrate Ketogenic diets: a case series. J Eat Disord. 2020 Jan 29;8:2. doi: 10.1186/s40337-020-0278-7. eCollection 2020.
citation: Norwitz NG, Sethi S, Palmer CM. Ketogenic diet as a metabolic treatment for mental illness. Curr Opin Endocrinol Diabetes Obes. 2020 Oct;27(5):269-274. doi: 10.1097/MED.0000000000000564.
citation: Yu B, Ozveren R, Sethi Dalai S. Ketogenic diet as a metabolic therapy for bipolar disorder: Clinical developments. Submitted to Journal of Affective Disorders. Research Square preprint March 2020: DOI is: 10.21203/rs.3.rs-334453/v1
citation: Brietzke E, Mansur RB, Subramaniapillai M, Balanza-Martinez V, Vinberg M, Gonzalez-Pinto A, Rosenblat JD, Ho R, McIntyre RS. Ketogenic diet as a metabolic therapy for mood disorders: Evidence and developments. Neurosci Biobehav Rev. 2018 Nov;94:11-16. doi: 10.1016/j.neubiorev.2018.07.020. Epub 2018 Jul 31.
citation: Sarnyai Z, Kraeuter AK, Palmer CM. Ketogenic diet for schizophrenia: clinical implication. Curr Opin Psychiatry. 2019 Sep;32(5):394-401. doi: 10.1097/YCO.0000000000000535.
citation: Sethi S, Wakeham D, Ketter T, Hooshmand F, Bjornstad J, Richards B, Westman E, Krauss RM, Saslow L. Ketogenic Diet Intervention on Metabolic and Psychiatric Health in Bipolar and Schizophrenia: A Pilot Trial. Psychiatry Res. 2024 May;335:115866. doi: 10.1016/j.psychres.2024.115866. Epub 2024 Mar 20.