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

Obesity Clinical Trial

Official title:

Impact of A Low-Carbohydrate, High-Fat, Ketogenic Diet on Obesity, Metabolic Abnormalities, and Psychiatric Symptoms on Patients With Bipolar Disorder (BPD)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05705063
• Other study ID #: 68493
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 30, 2023
• Est. completion date: December 30, 2024

Study information

• Verified date: January 2023
• Source: Stanford University
• Contact: Diane E Wakeham, PhD
• Phone: 650-736-5243
• Email: wakeham[@]stanford.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: December 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Bipolar and Related Disorders
• Bipolar Depression
• Bipolar Disorder
• Bipolar Disorder I
• Bipolar I Disorder
• Bipolar II Disorder
• Disease
• Ketogenic Dieting
• Metabolic Diseases
• Metabolic Syndrome
• Obesity
• Weight Gain

Intervention

Other:
• LCHF Ketogenic Diet
Low Carbohydrate, Moderate Protein, High Fat Ketogenic Dietary Intervention 6 weeks

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

References & Publications (8)

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. — View Citation

Carmen M, Safer DL, Saslow LR, Kalayjian T, Mason AE, Westman EC, Sethi Dalai 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Weight from Baseline	Weight recorded weekly during study	Baseline, 6 weeks
Primary	Change in Waist Circumference from Baseline	Waist circumference recorded at each visit during study	Baseline, 6 weeks
Primary	Change in Heart Rate from Baseline	Heart rate recorded at each visit during study	Baseline, 6 weeks
Primary	Change in Blood Pressure from Baseline	Blood pressure recorded weekly during study	Baseline, 6 weeks
Primary	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
Primary	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
Primary	Change in Hemoglobin A1c from Baseline	Blood measurement of Hemoglobin A1c recorded at baseline and study end	Baseline, 6 weeks
Primary	Change in Insulin Resistance Measure (HOMA-IR) from Baseline	HOMA-IR calculated from blood measurements recorded at baseline and study end	Baseline, 6 weeks
Primary	Change in Inflammatory Marker (hs-CRP) from Baseline	Blood measurement of hs-CRP recorded at baseline and study end	Baseline, 6 weeks
Primary	Change in Lipid Profile (TG) from Baseline	Blood levels of Lipid Triglycerides (TG) recorded at baseline and study end	Baseline, 6 weeks
Primary	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
Primary	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	Change in Clinical Mood Monitoring from Baseline	Change in Clinical Mood Monitoring Psychiatric Index from Baseline	Baseline, 6 weeks
Secondary	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)	Baseline, 6 weeks
Secondary	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)	Baseline, 6 weeks
Secondary	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)	Baseline, 6 weeks
Secondary	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)	Baseline, 6 weeks
Secondary	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)	Baseline, 6 weeks
Secondary	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)	Baseline, 6 weeks
Secondary	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)	Baseline, 6 weeks

External Links

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