Clinical trial NCT05705063: 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
Overall status: UNKNOWN
Phase: NA
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
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2023-01-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single Group Assignment
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Change in Weight from Baseline
timeFrame: Baseline, 6 weeks
measure: Change in Waist Circumference from Baseline
timeFrame: Baseline, 6 weeks
measure: Change in Heart Rate from Baseline
timeFrame: Baseline, 6 weeks
measure: Change in Blood Pressure from Baseline
timeFrame: Baseline, 6 weeks
measure: Change in Visceral Fat Mass from Baseline
timeFrame: Baseline, 6 weeks
measure: Change in Body Fat Mass from Baseline
timeFrame: Baseline, 6 weeks
measure: Change in Hemoglobin A1c from Baseline
timeFrame: Baseline, 6 weeks
measure: Change in Insulin Resistance Measure (HOMA-IR) from Baseline
timeFrame: Baseline, 6 weeks
measure: Change in Inflammatory Marker (hs-CRP) from Baseline
timeFrame: Baseline, 6 weeks
measure: Change in Lipid Profile (TG) from Baseline
timeFrame: Baseline, 6 weeks
measure: Change in Lipid Profile small LDL from Baseline
timeFrame: Baseline, 6 weeks
measure: Change in Lipid Profile HDL from Baseline
timeFrame: Baseline, 6 weeks
Secondary outcomes:
measure: Change in Clinical Mood Monitoring from Baseline
timeFrame: Baseline, 6 weeks
measure: Change in Clinical Global Impression from Baseline
timeFrame: Baseline, 6 weeks
measure: Change Generalized Anxiety Disorder from Baseline
timeFrame: Baseline, 6 weeks
measure: Change in Depression from Baseline
timeFrame: Baseline, 6 weeks
measure: Change in Global Assessment of Functioning from Baseline
timeFrame: Baseline, 6 weeks
measure: Change in Quality of Life from Baseline
timeFrame: Baseline, 6 weeks
measure: Change in Quality of Sleep from Baseline
timeFrame: Baseline, 6 weeks
measure: Change in Eating Behavior from Baseline
timeFrame: Baseline, 6 weeks
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University Dept Psychiatry and Behavioral Sciences
name: Shebani Sethi, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.
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.