Child Bipolar Network Ketogenic Diet Approach to Bipolar Disorder in Adolescents

About

Brief Summary

The present study is an open trial of ketogenic diets for adolescents and young adults (ages 12-21 yrs) in the depressive or mixed phases of bipolar disorder (BD). The investigators aim to determine whether combining standard of care pharmacological treatment for bipolar spectrum disorders with a 16-week ketogenic diet is well-tolerated and associated with improvements in depression, inflammatory and metabolic indicators, and executive functioning over the study period.

The experimental treatment in this study is a 16-week full ketogenic diet. Four study sites (UCLA, U Cincinnati, U Colorado and U Pittsburgh) will recruit 80 total youth (20 each) from bipolar specialty clinics. All youth eligible for the ketogenic therapy will be provided with the ketogenic diet and standard of care pharmacological treatment. During the diet therapy youth will be seen by a study child/adolescent psychiatrist at least once a month (and more frequently when needed), with the psychiatrist recommending and providing side effects monitoring and pharmacotherapy as clinically indicated.

The youth and caregivers will also meet with an expert dietitian who will coach all youth on maintaining the ketogenic diet (low carbs, high fats, medium protein) and making sure the child is tolerating the diet and getting enough liquid and nutrients, following the practice guidelines of the International Ketogenic Diet Study Group for treating youth. All youth and involved caregivers will also be provided will at least one motivational enhancement session to support them in goal setting and completion of the study elements.

Throughout the study the investigators will assess metabolic (e.g., blood ketones, HOMA-IR) and inflammatory indicators (e.g., C-reactive protein), both for safety reasons and to assess correlates of symptomatic change. Independent evaluators will assess youth every month regarding their symptoms (depression, mania, anxiety, psychosis), psychosocial functioning, and quality of life.

The investigators anticipate that the pilot will transpire over 24 months and be an important step toward establishing feasibility and acceptability of ketogenic therapy for this population, not only in terms of diet administration and compliance but also for obtaining symptomatic, metabolic and inflammatory measurements.

Primary Purpose

Treatment

Study Type

Interventional

Phase

N/A

Eligibility

Gender

All

Healthy Volunteers

No

Minimum Age

12 Years

Maximum Age

21 Years

Inclusion Criteria:

Youth must be ages 12 to 21 years old and speak English
Youth must be appropriate for outpatient treatment (i.e., not a danger to self or others; not acutely psychotic, suicidal or manic; not in need of partial or full hospitalization)
Youth must have a current BSD (bipolar I, II per DSM-5 criteria (Association, 2013) or other specified BSD by the University of Pittsburgh diagnostic criteria (Birmaher et al., 2006). The Pittsburgh other specified BSD criteria require recurrent and distinct 1-3 day periods (minimum 4 hours/day) in which there has been abnormally elevated, expansive, or irritable mood plus two (three, if irritable mood only) symptoms of mania that caused a change in functioning and totaled at least 4 days in the child's lifetime
Active symptoms: In the 2 weeks prior to study intake, participants must have had weekly depression Psychiatric Status Ratings (PSRs) of 3 (moderate) or higher (using the 1-6 depression severity scales from the Adolescent Longitudinal Follow-up Evaluation, or A-LIFE); or an interview-based Children's Depression Rating Scale, Revised (CDRS-R) score covering the prior 2 weeks of > 20. Youth may also enter with mixed symptoms (e.g., simultaneous elevations of > 3 on the PSR depression and hypomania scales, with Young Mania Rating Scale scores of 12 or higher), without meeting criteria for a full manic episode in the past month.
Participants must continue to meet the study's active symptom criteria when beginning the phase II keto "ramp-up" phase: a depression PSR rating of 3 or higher over the prior 2 weeks, and a CDRS-R score covering the prior 2 weeks of > 20.
Youth/parents must be willing to participate in evaluation and medication management sessions with a study psychiatrist and the study dietitian for assessment of the diet and side effects.
Youth under 18 years old must have at least one English-speaking parent or other caregiving family member consenting to participate in the study and available for consultation if needed
Youth and (for minors) all parents/legal guardians with health care decision making rights must express willingness to have the youth be in the study and try the keto therapy, assuming that the youth is eligible. The team must ascertain that the participating minor's youth/caregiver is likely to make a strong effort to adhere to the study's protocol.

Exclusion Criteria:

The youth must not have any of the following needs or conditions for which the keto diet may be contraindicated:

pregnancy or breastfeeding
underweight (BMI below 18.5) or wasting syndrome (e.g., anorexia cachexia)
current or history of anorexia nervosa
current disordered eating (bulimia or binge eating disorder)
autism spectrum disorder diagnosis level 2 or greater (more than mild)
cardiac issues, including history of arrhythmia, or cardiovascular or cerebrovascular disease
type I and type II diabetes
history of seizures/epilepsy
history of stroke or cancer
unstable respiratory condition
severe gastroesophageal reflux (GERD; painful/impairing despite prescription medication)
substance use disorder (with an exception for mild cannabis or nicotine use disorders)
history of kidney stones/disease
diseases involving the pancreas, liver, gallbladder or thyroid, including Von Gierke's glycogen storage disease
Condition with high cholesterol of triglycerides will prompt physician review of eligibility (LDL>190 or triglycerides>500)
genetic metabolic disorders: either porphyria (impacting the body's ability to make hemoglobin) or fatty acid oxidation disorder (FAOD)
rare conditions of defective ketone production or breakdown (carnitine deficiency, carnitine palmitoyl-transferase deficiency, carnitine-acylcarnitine translocase deficiency, mitochondrial fatty acid β-oxidation disorders, Succinyl-CoA:3-ketoacid CoA transferase deficiency (SCOT), or pyruvate carboxylase deficiency)
youth must not be taking SGLT-2 inhibitors (e.g., canagliflozin), insulin, or sulfonylureas (to avoid hypogycemia), or Antihypertensive medication (e.g., lisinopril/ACE Angiotensin inhibitors ending in "pril", ARB Angiotensin II receptor blockers, spironolactone/Aldactone, Thiazide-type diuretics)