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

Primary Purpose

Bipolar Disorder I, Bipolar II Disorder, Bipolar I Disorder

Status
Not yet recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
LCHF Ketogenic Diet
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bipolar Disorder I

Eligibility Criteria

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

Inclusion Criteria: Male or female, 18 to 75 years of age. Able to provide informed consent. Meet DSM V criteria for diagnosis with Bipolar Disorder (BPD), any subtype, for > 1 year and clinically stable (with no hospitalization for past 3 months) Participants may currently be on a stable and adequate dose of SSRI antidepressant therapy or other psychiatric medications. Concurrent hypnotic therapy (e.g., with zolpidem, zaleplon, melatonin, or trazodone) will be allowed if the therapy has been stable for at least 4 weeks prior to screening and if it is expected to remain stable. Participants may choose to not be on antidepressant therapy for the study duration, or to be switched from other classes to a medication from the SSRI class. currently taking SSRI or 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) In good general health, as ascertained by medical history. If female, a status of non-childbearing potential or use of an acceptable form of birth control. The form of birth control will be documented at screening and baseline. willing to consent to all study procedures and attend follow-up appointments and motivated to follow 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 6-week trial Exclusion Criteria: Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study. Female that is pregnant or breastfeeding. Female with a positive pregnancy test at participation. comorbidity of developmental delay or Cognitive impairment (as noted by previous diagnoses-including dementia). Current diagnosis of a Substance Use Disorder (Abuse or Dependence, as defined by DSM-IV-TR), with the exception of nicotine dependence, at screening or within six months prior to screening. History of positive screening urine test for drugs of abuse at screening: cocaine, amphetamines, barbiturates, opiates. Current (or chronic) use of opiates. in a current severe mood or psychotic state when entering the study that would prohibit compliance with study visits or dietary program. Considered at significant risk for suicide during the course of the study. any one who has been hospitalized or taken clozapine at doses above 550mg over the past 3 months Has a clinically significant abnormality on the screening examination that might affect safety, study participation, or confound interpretation of study results. Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation. Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation. inability to complete baseline measurements severe renal or hepatic insufficiency cardiovascular dysfunction, including diagnosis of: Congestive heart failure Angina Arrhythmias Cardiomyopathy Valvular heart disease History of cardiovascular disease or cardiac event. 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 School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bipolar Patients

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 Weight from Baseline
Weight recorded weekly during study
Change in Waist Circumference from Baseline
Waist circumference recorded at each visit during study
Change in Heart Rate from Baseline
Heart rate recorded at each visit during study
Change in Blood Pressure from Baseline
Blood pressure recorded weekly during study
Change in Visceral Fat Mass from Baseline
Kg visceral fat in body composition (SECA or Inbody) recorded 2-3 times during study
Change in Body Fat Mass from Baseline
Kg body fat in body composition (SECA or Inbody) recorded 2-3 times during study
Change in Hemoglobin A1c from Baseline
Blood measurement of Hemoglobin A1c recorded at baseline and study end
Change in Insulin Resistance Measure (HOMA-IR) from Baseline
HOMA-IR calculated from blood measurements recorded at baseline and study end
Change in Inflammatory Marker (hs-CRP) from Baseline
Blood measurement of hs-CRP recorded at baseline and study end
Change in Lipid Profile (TG) from Baseline
Blood levels of Lipid Triglycerides (TG) recorded at baseline and study end
Change in Lipid Profile small LDL from Baseline
Blood levels of small, low density lipoprotein cholesterol (LDL-C) recorded at baseline and study end
Change in Lipid Profile HDL from Baseline
Blood levels of high density lipoprotein cholesterol (HDL-C) recorded at baseline and study end

Secondary Outcome Measures

Change in Clinical Mood Monitoring from Baseline
Change in Clinical Mood Monitoring Psychiatric Index from Baseline
Change in Clinical Global Impression from Baseline
Change in Clinical Global Impression (CGI) Psychiatric Index from Baseline; 1-7 scale. (1= not at all ill, 7= among the most extremely ill patients)
Change Generalized Anxiety Disorder from Baseline
Change in General Anxiety Disorder (GAD-7) scale from Baseline. 0-15+ scale. (0= no anxiety, 15+= severe anxiety)
Change in Depression from Baseline
Change in Depression on Patient Health Questionnaire (PHQ-9) scale from Baseline; Score range 0-27 (0= no depression, 27= severe depression)
Change in Global Assessment of Functioning from Baseline
Change in Global Assessment of Functioning (GAF) scale from baseline; 1-100 scale (1= persistent danger of hurting self or others, 100= superior functioning)
Change in Quality of Life from Baseline
Change in Manchester Quality of Life (MANSA) scale 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)
Change in Quality of Sleep from Baseline
Change in Pittsburgh Sleep Quality Index (PSQI) from baseline; 0-21 scale (<5=good sleeper; 5+= meaningfully disturbed sleep or poor sleeper)
Change in Eating Behavior from Baseline
Change in Binge Eating Scale (BES) from Baseline; 0-46 scale (<17 minimal binge eating problems, >27 severe binge eating problems)

Full Information

First Posted
January 21, 2023
Last Updated
January 21, 2023
Sponsor
Stanford University
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1. Study Identification

Unique Protocol Identification Number
NCT05705063
Brief Title
Impact of a Ketogenic Diet on Metabolic and Psychiatric Health in Patients With Bipolar Illness
Official Title
Impact of A Low-Carbohydrate, High-Fat, Ketogenic Diet on Obesity, Metabolic Abnormalities, and Psychiatric Symptoms on Patients With Bipolar Disorder (BPD)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 30, 2023 (Anticipated)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
December 30, 2024 (Anticipated)

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
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
To initiate a low-carbohydrate, high-fat (LCHF) or ketogenic dietary (KD) intervention among a cohort of outpatients with 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 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
Bipolar Disorder I, Bipolar II Disorder, Bipolar I Disorder, Bipolar Disorder, Bipolar Depression, Bipolar and Related Disorders, Bipolar Disorder, Type 1, Bipolar Disorder, Type 2, Bipolar Disorder, Mixed, Obesity, Metabolic Syndrome, Ketogenic Dieting, Weight Gain, Brain Metabolic Disorder, Psychotropic Agents Causing Adverse Effects in Therapeutic Use

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Bipolar Patients
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 6 weeks
Primary Outcome Measure Information:
Title
Change in Weight from Baseline
Description
Weight recorded weekly during study
Time Frame
Baseline, 6 weeks
Title
Change in Waist Circumference from Baseline
Description
Waist circumference recorded at each visit during study
Time Frame
Baseline, 6 weeks
Title
Change in Heart Rate from Baseline
Description
Heart rate recorded at each visit during study
Time Frame
Baseline, 6 weeks
Title
Change in Blood Pressure from Baseline
Description
Blood pressure recorded weekly during study
Time Frame
Baseline, 6 weeks
Title
Change in Visceral Fat Mass from Baseline
Description
Kg visceral fat in body composition (SECA or Inbody) recorded 2-3 times during study
Time Frame
Baseline, 6 weeks
Title
Change in Body Fat Mass from Baseline
Description
Kg body fat in body composition (SECA or Inbody) recorded 2-3 times during study
Time Frame
Baseline, 6 weeks
Title
Change in Hemoglobin A1c from Baseline
Description
Blood measurement of Hemoglobin A1c recorded at baseline and study end
Time Frame
Baseline, 6 weeks
Title
Change in Insulin Resistance Measure (HOMA-IR) from Baseline
Description
HOMA-IR calculated from blood measurements recorded at baseline and study end
Time Frame
Baseline, 6 weeks
Title
Change in Inflammatory Marker (hs-CRP) from Baseline
Description
Blood measurement of hs-CRP recorded at baseline and study end
Time Frame
Baseline, 6 weeks
Title
Change in Lipid Profile (TG) from Baseline
Description
Blood levels of Lipid Triglycerides (TG) recorded at baseline and study end
Time Frame
Baseline, 6 weeks
Title
Change in Lipid Profile small LDL from Baseline
Description
Blood levels of small, low density lipoprotein cholesterol (LDL-C) recorded at baseline and study end
Time Frame
Baseline, 6 weeks
Title
Change in Lipid Profile HDL from Baseline
Description
Blood levels of high density lipoprotein cholesterol (HDL-C) recorded at baseline and study end
Time Frame
Baseline, 6 weeks
Secondary Outcome Measure Information:
Title
Change in Clinical Mood Monitoring from Baseline
Description
Change in Clinical Mood Monitoring Psychiatric Index from Baseline
Time Frame
Baseline, 6 weeks
Title
Change in Clinical Global Impression from Baseline
Description
Change in Clinical Global Impression (CGI) Psychiatric Index from Baseline; 1-7 scale. (1= not at all ill, 7= among the most extremely ill patients)
Time Frame
Baseline, 6 weeks
Title
Change Generalized Anxiety Disorder from Baseline
Description
Change in General Anxiety Disorder (GAD-7) scale from Baseline. 0-15+ scale. (0= no anxiety, 15+= severe anxiety)
Time Frame
Baseline, 6 weeks
Title
Change in Depression from Baseline
Description
Change in Depression on Patient Health Questionnaire (PHQ-9) scale from Baseline; Score range 0-27 (0= no depression, 27= severe depression)
Time Frame
Baseline, 6 weeks
Title
Change in Global Assessment of Functioning from Baseline
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, 6 weeks
Title
Change in Quality of Life from Baseline
Description
Change in Manchester Quality of Life (MANSA) scale 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)
Time Frame
Baseline, 6 weeks
Title
Change in Quality of Sleep from Baseline
Description
Change in Pittsburgh Sleep Quality Index (PSQI) from baseline; 0-21 scale (<5=good sleeper; 5+= meaningfully disturbed sleep or poor sleeper)
Time Frame
Baseline, 6 weeks
Title
Change in Eating Behavior from Baseline
Description
Change in Binge Eating Scale (BES) from Baseline; 0-46 scale (<17 minimal binge eating problems, >27 severe binge eating problems)
Time Frame
Baseline, 6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female, 18 to 75 years of age. Able to provide informed consent. Meet DSM V criteria for diagnosis with Bipolar Disorder (BPD), any subtype, for > 1 year and clinically stable (with no hospitalization for past 3 months) Participants may currently be on a stable and adequate dose of SSRI antidepressant therapy or other psychiatric medications. Concurrent hypnotic therapy (e.g., with zolpidem, zaleplon, melatonin, or trazodone) will be allowed if the therapy has been stable for at least 4 weeks prior to screening and if it is expected to remain stable. Participants may choose to not be on antidepressant therapy for the study duration, or to be switched from other classes to a medication from the SSRI class. currently taking SSRI or 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) In good general health, as ascertained by medical history. If female, a status of non-childbearing potential or use of an acceptable form of birth control. The form of birth control will be documented at screening and baseline. willing to consent to all study procedures and attend follow-up appointments and motivated to follow 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 6-week trial Exclusion Criteria: Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study. Female that is pregnant or breastfeeding. Female with a positive pregnancy test at participation. comorbidity of developmental delay or Cognitive impairment (as noted by previous diagnoses-including dementia). Current diagnosis of a Substance Use Disorder (Abuse or Dependence, as defined by DSM-IV-TR), with the exception of nicotine dependence, at screening or within six months prior to screening. History of positive screening urine test for drugs of abuse at screening: cocaine, amphetamines, barbiturates, opiates. Current (or chronic) use of opiates. in a current severe mood or psychotic state when entering the study that would prohibit compliance with study visits or dietary program. Considered at significant risk for suicide during the course of the study. any one who has been hospitalized or taken clozapine at doses above 550mg over the past 3 months Has a clinically significant abnormality on the screening examination that might affect safety, study participation, or confound interpretation of study results. Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation. Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation. inability to complete baseline measurements severe renal or hepatic insufficiency cardiovascular dysfunction, including diagnosis of: Congestive heart failure Angina Arrhythmias Cardiomyopathy Valvular heart disease History of cardiovascular disease or cardiac event. any other medical condition that may make either diet dangerous as determined by the study medical team (e.g. anorexia nervosa)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Diane E Wakeham, PhD
Phone
650-736-5243
Email
wakeham@stanford.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Shebani Sethi, MD
Phone
650-721-4419
Email
shebanis@stanford.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shebani Sethi, MD
Organizational Affiliation
Stanford University Dept Psychiatry and Behavioral Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94704
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Diane E Wakeham, PhD
Phone
650-736-5243
Email
wakeham@stanford.edu
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
650-736-5243
First Name & Middle Initial & Last Name & Degree
Shebani Sethi, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
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
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
36245868
Citation
Unwin J, Delon C, Giaever H, Kennedy C, Painschab M, Sandin F, Poulsen CS, Wiss DA. Low carbohydrate and psychoeducational programs show promise for the treatment of ultra-processed food addiction. Front Psychiatry. 2022 Sep 28;13:1005523. doi: 10.3389/fpsyt.2022.1005523. eCollection 2022.
Results Reference
background
PubMed Identifier
35873236
Citation
Danan A, Westman EC, Saslow LR, Ede G. The Ketogenic Diet for Refractory Mental Illness: A Retrospective Analysis of 31 Inpatients. Front Psychiatry. 2022 Jul 6;13:951376. doi: 10.3389/fpsyt.2022.951376. eCollection 2022.
Results Reference
background
PubMed Identifier
36483840
Citation
Sethi S, Ford JM. The Role of Ketogenic Metabolic Therapy on the Brain in Serious Mental Illness: A Review. J Psychiatr Brain Sci. 2022;7(5):e220009. doi: 10.20900/jpbs.20220009. Epub 2022 Oct 31.
Results Reference
background
PubMed Identifier
36501104
Citation
Imdad K, Abualait T, Kanwal A, AlGhannam ZT, Bashir S, Farrukh A, Khattak SH, Albaradie R, Bashir S. The Metabolic Role of Ketogenic Diets in Treating Epilepsy. Nutrients. 2022 Nov 29;14(23):5074. doi: 10.3390/nu14235074.
Results Reference
background
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
result
Links:
URL
https://doi.org/10.1016/j.jadr.2022.100457
Description
Ketogenic diet as a metabolic therapy for bipolar disorder: Clinical developments

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

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