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

NCT05705063 | Unknown

• 1 other identifier: 68493
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (12)

• Change in Weight from Baseline

  Weight recorded weekly during study

  Baseline, 6 weeks

• Change in Waist Circumference from Baseline

  Waist circumference recorded at each visit during study

  Baseline, 6 weeks

• Change in Heart Rate from Baseline

  Heart rate recorded at each visit during study

  Baseline, 6 weeks

• Change in Blood Pressure from Baseline

  Blood pressure recorded weekly during study

  Baseline, 6 weeks

• Change in Visceral Fat Mass from Baseline

  Kg visceral fat in body composition (SECA or Inbody) recorded 2-3 times during study

  Baseline, 6 weeks

• Change in Body Fat Mass from Baseline

  Kg body fat in body composition (SECA or Inbody) recorded 2-3 times during study

  Baseline, 6 weeks

• Change in Hemoglobin A1c from Baseline

  Blood measurement of Hemoglobin A1c recorded at baseline and study end

  Baseline, 6 weeks

• Change in Insulin Resistance Measure (HOMA-IR) from Baseline

  HOMA-IR calculated from blood measurements recorded at baseline and study end

  Baseline, 6 weeks

• Change in Inflammatory Marker (hs-CRP) from Baseline

  Blood measurement of hs-CRP recorded at baseline and study end

  Baseline, 6 weeks

• Change in Lipid Profile (TG) from Baseline

  Blood levels of Lipid Triglycerides (TG) recorded at baseline and study end

  Baseline, 6 weeks

• Change in Lipid Profile small LDL from Baseline

  Blood levels of small, low density lipoprotein cholesterol (LDL-C) recorded at baseline and study end

  Baseline, 6 weeks

• Change in Lipid Profile HDL from Baseline

  Blood levels of high density lipoprotein cholesterol (HDL-C) recorded at baseline and study end

  Baseline, 6 weeks

Secondary Outcomes (8)

• Change in Clinical Mood Monitoring from Baseline

  Baseline, 6 weeks

• Change in Clinical Global Impression from Baseline

  Baseline, 6 weeks

• Change Generalized Anxiety Disorder from Baseline

  Baseline, 6 weeks

• Change in Depression from Baseline

  Baseline, 6 weeks

• Change in Global Assessment of Functioning from Baseline

  Baseline, 6 weeks

Study Arms (1)

Bipolar Patients

EXPERIMENTAL

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

Other: LCHF Ketogenic Diet

Interventions

LCHF Ketogenic Diet OTHER

Low Carbohydrate, Moderate Protein, High Fat Ketogenic Dietary Intervention 6 weeks

Bipolar Patients

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94704, United States

Location

Related Publications (8)

• 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.

  PMID: 32010444 BACKGROUND

• 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.

  PMID: 32773571 BACKGROUND

• 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.

  PMID: 30075165 BACKGROUND

• 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.

  PMID: 36245868 BACKGROUND

• 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.

  PMID: 35873236 BACKGROUND

• 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.

  PMID: 36483840 BACKGROUND

• 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.

  PMID: 36501104 BACKGROUND

• 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.

  PMID: 32773576 RESULT

Related Links

• Ketogenic diet as a metabolic therapy for bipolar disorder: Clinical developments

MeSH Terms

Conditions

Bipolar Disorder; Bipolar and Related Disorders; Obesity; Metabolic Syndrome; Weight Gain; Brain Diseases, Metabolic

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Body Weight Changes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Shebani Sethi, MD

  Stanford University Dept Psychiatry and Behavioral Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Diane E Wakeham, PhD

CONTACT

650-736-5243; wakeham@stanford.edu

Shebani Sethi, MD

CONTACT

650-721-4419; shebanis@stanford.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: CLINICAL ASSISTANT PROFESSOR OF PSYCHIATRY AND BEHAVIORAL SCIENCES

Model Details: Single Group Assignment

Study Record Dates

• First Submitted: January 21, 2023
• First Posted: January 30, 2023
• Study Start: January 30, 2023
• Primary Completion: June 30, 2024
• Study Completion: December 30, 2024
• Last Updated: January 30, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)