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

Primary Purpose

Obesity, Ketogenic Dieting, Metabolic Syndrome

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

LCHF, Ketogenic Diet

About this trial

This is an interventional treatment trial for Obesity

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Stanford University Department of Psychiatry & Behavioral Sciences

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ketogenic Diet 16 Week Group

Arm Description

Patients follow ketogenic diet for 16 weeks, with monitoring of physical and psychological health and coaching support

Outcomes

Primary Outcome Measures

Change in heart rate from baseline

Heart rate recorded at 9 visits during study

Change in blood pressure from baseline

Blood pressure recorded at 9 visits during study

Change in weight from baseline

Weight recorded at 9 visits during study

Change in waist circumference from baseline

waist circumference measured at 9 visits during study

Change in visceral fat mass from baseline

Body composition (SECA) recorded at 5 visits during study

Change in body fat mass from baseline

Body composition (SECA) recorded at 5 visits during study

Percent Change in Hemoglobin A1c from baseline

Hemoglobin A1c recorded at initial and final visits

Change in insulin resistance measure (HOMA-IR) from baseline

HOMA-IR measured at initial and final visits

Change in inflammatory marker (hsCRP) from baseline

hsCRP measured at initial and final visits

Change in lipid profile TG (triglycerides) from baseline

Lipid profile TG measured at initial and final visits

Change in lipid profile small LDL (small dense LDL) from baseline

Lipid profile small LDL measured at initial and final visits

Change in lipid profile (HDL) from baseline

Lipid profile HDL measured at initial and final visits

Secondary Outcome Measures

Psychiatric Indices - Mood

Change in Mood Qualitative Score (Clinical Mood Monitoring) from baseline

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)

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)

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)

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)

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)

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)

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)

Full Information

NCT ID

NCT03935854

First Posted

April 30, 2019

Last Updated

December 6, 2022

Sponsor

Stanford University

1. Study Identification

Unique Protocol Identification Number

NCT03935854

Brief Title

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

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Completed

Study Start Date

February 13, 2019 (Actual)

Primary Completion Date

August 11, 2022 (Actual)

Study Completion Date

August 11, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Stanford University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

23 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ketogenic Diet 16 Week Group

Arm Type

Experimental

Arm Description

Patients follow ketogenic diet for 16 weeks, with monitoring of physical and psychological health and coaching support

Intervention Type

Other

Intervention Name(s)

LCHF, Ketogenic Diet

Intervention Description

Low Carbohydrate, Moderate Protein, High Fat Ketogenic Dietary Intervention 16 weeks

Primary Outcome Measure Information:

Title

Change in heart rate from baseline

Description

Heart rate recorded at 9 visits during study

Time Frame

Baseline, 16 weeks

Title

Change in blood pressure from baseline

Description

Blood pressure recorded at 9 visits during study

Time Frame

Baseline, 16 weeks

Title

Change in weight from baseline

Description

Weight recorded at 9 visits during study

Time Frame

Baseline, 16 weeks

Title

Change in waist circumference from baseline

Description

waist circumference measured at 9 visits during study

Time Frame

Baseline, 16 weeks

Title

Change in visceral fat mass from baseline

Description

Body composition (SECA) recorded at 5 visits during study

Time Frame

Baseline, 16 weeks

Title

Change in body fat mass from baseline

Description

Body composition (SECA) recorded at 5 visits during study

Time Frame

Baseline, 16 weeks

Title

Percent Change in Hemoglobin A1c from baseline

Description

Hemoglobin A1c recorded at initial and final visits

Time Frame

Baseline, 16 weeks

Title

Change in insulin resistance measure (HOMA-IR) from baseline

Description

HOMA-IR measured at initial and final visits

Time Frame

Baseline, 16 weeks

Title

Change in inflammatory marker (hsCRP) from baseline

Description

hsCRP measured at initial and final visits

Time Frame

Baseline, 16 weeks

Title

Change in lipid profile TG (triglycerides) from baseline

Description

Lipid profile TG measured at initial and final visits

Time Frame

Baseline, 16 weeks

Title

Change in lipid profile small LDL (small dense LDL) from baseline

Description

Lipid profile small LDL measured at initial and final visits

Time Frame

Baseline, 16 weeks

Title

Change in lipid profile (HDL) from baseline

Description

Lipid profile HDL measured at initial and final visits

Time Frame

Baseline,16 weeks

Secondary Outcome Measure Information:

Title

Psychiatric Indices - Mood

Description

Change in Mood Qualitative Score (Clinical Mood Monitoring) from baseline

Time Frame

Baseline, 16 weeks

Title

Psychiatric Indices- Clinical Global Impression

Description

Change in Clinical Global Impression Scales (CGI) from baseline 1-7 scale. 1= not at all ill, 7= among the most extremely ill patients)

Time Frame

Baseline, 16 weeks

Title

Generalized Anxiety Disorder - GAD-7 Anxiety

Description

Change in Generalized Anxiety Symptom (GAD-7) scale from baseline. 0-15+ scale. (0= no anxiety, 15+= severe anxiety)

Time Frame

Baseline, 16 weeks

Title

Patient Health Questionnaire - PHQ-9 Depression

Description

Change in Patient Health Questionnaire (PHQ-9) from baseline. Score range 0-27 (0= no depression, 27= severe depression)

Time Frame

Baseline, 16 weeks

Title

Psychiatric Indices- Global Assessment of Functioning

Description

Change in Global Assessment of Functioning (GAF) Scale from baseline. 1-100 scale (1= persistent danger of hurting self or others, 100= superior functioning)

Time Frame

Baseline, 16 weeks

Title

Psychiatric Indices- Quality of Life

Description

Time Frame

Baseline, 16 weeks

Title

Psychiatric Indices- BPRS

Description

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)

Time Frame

Baseline, 16 weeks

Title

Pittsburgh Sleep Quality Index - PSQI

Description

Change in Pittsburgh Sleep Quality Index from baseline. 0-21 scale (<5=good sleeper; 5+= meaningfully disturbed sleep or poor sleeper)

Time Frame

Baseline, 16 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Shebani Sethi Dalai, MD

Organizational Affiliation

Stanford University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Stanford University Department of Psychiatry & Behavioral Sciences

City

Stanford

State/Province

California

ZIP/Postal Code

94305

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

32773576

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.

Results Reference

background

PubMed Identifier

32010444

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. Erratum In: J Eat Disord. 2023 Sep 29;11(1):171.

Results Reference

background

PubMed Identifier

32773571

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.

Results Reference

background

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

Results Reference

background

PubMed Identifier

30075165

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.

Results Reference

background

PubMed Identifier

31192814

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.

Results Reference

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

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