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

NCT ID: NCT05705063

Last Updated: 2023-01-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-30
• Study Completion Date: 2024-12-30

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bipolar Patients

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

Group Type: EXPERIMENTAL

LCHF Ketogenic Diet

Intervention Type: OTHER

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

Interventions

LCHF Ketogenic Diet

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Male or female, 18 to 75 years of age.

2. Able to provide informed consent.

3. 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)

4. 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.

5. 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)

6. In good general health, as ascertained by medical history.

7. 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.

8. willing to consent to all study procedures and attend follow-up appointments and motivated to follow dietary program.

9. Sufficient control over their food intake to adhere to study diets.

10. willingness to regularly monitor blood pressure, glucose, dietary intake, and body weight over 6-week trial

Exclusion Criteria

1. Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study.

2. Female that is pregnant or breastfeeding.

3. Female with a positive pregnancy test at participation.

4. comorbidity of developmental delay or Cognitive impairment (as noted by previous diagnoses-including dementia).

5. 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.

6. History of positive screening urine test for drugs of abuse at screening: cocaine, amphetamines, barbiturates, opiates.

7. Current (or chronic) use of opiates.

8. in a current severe mood or psychotic state when entering the study that would prohibit compliance with study visits or dietary program.

9. Considered at significant risk for suicide during the course of the study.

10. any one who has been hospitalized or taken clozapine at doses above 550mg over the past 3 months

11. Has a clinically significant abnormality on the screening examination that might affect safety, study participation, or confound interpretation of study results.

12. 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.

13. Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation.

14. inability to complete baseline measurements

15. severe renal or hepatic insufficiency

16. cardiovascular dysfunction, including diagnosis of:

1. Congestive heart failure

2. Angina

3. Arrhythmias

4. Cardiomyopathy

5. Valvular heart disease

6. History of cardiovascular disease or cardiac event.

17. any other medical condition that may make either diet dangerous as determined by the study medical team (e.g. anorexia nervosa)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Shebani Sethi

CLINICAL ASSISTANT PROFESSOR OF PSYCHIATRY AND BEHAVIORAL SCIENCES

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shebani Sethi, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University Dept Psychiatry and Behavioral Sciences

Locations

Stanford University School of Medicine

Stanford, California, United States

Countries

United States

Central Contacts

Diane E Wakeham, PhD

Role: CONTACT

wakeham@stanford.edu

650-736-5243

Shebani Sethi, MD

Role: CONTACT

shebanis@stanford.edu

650-721-4419

Facility Contacts

Diane E Wakeham, PhD

Role: primary

wakeham@stanford.edu

650-736-5243

Study Coordinator

Role: backup

650-736-5243

References

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.

Reference Type: BACKGROUND

PMID: 32010444 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32773571 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30075165 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 36245868 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 35873236 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 36483840 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 36501104 (View on PubMed)

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.

Reference Type: RESULT

PMID: 32773576 (View on PubMed)

Related Links

https://doi.org/10.1016/j.jadr.2022.100457

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

Other Identifiers

68493

Identifier Type: -

Identifier Source: org_study_id