Child Bipolar Network Ketogenic Diet Approach to Bipolar Disorder in Adolescents

NCT06920940 | Recruiting

• 1 other identifier: IRB#24-5711
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 4

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.

Conditions

Bipolar Disorder (BD); Bipolar Disorder NOS; Bipolar Disorder I or II; Bipolar Spectrum Disorder; Adolescents

Keywords

ketogenic; treatment; diet; keto

Outcome Measures

Primary Outcomes (5)

• Diet Adherence

  The investigators will assess diet adherence primarily by the proportion of youth who maintain an average weekly ketone level of 1 mmol/L or above, as measured through daily blood ketone assays using the Keto Mojo device, a Bluetooth-enabled ketone and glucose testing kit.

  From initiation of ketogenic therapy to the end of treatment (up to 16 weeks)

• Diet Tolerance

  The investigators will assess diet tolerance primarily by calculating the proportion of youth staying on the diet. The investigators hypothesize 70-80% of youth will tolerate staying on the keto therapy throughout the 16-week treatment as verified by youth self report of continuance of the diet (combined with parent report if applicable). Youth with multiple weekly ketone levels at .5 mmol/L or below will be considered diet intolerant regardless of self-report.

  From initiation of ketogenic therapy to the end of treatment (up to 16 weeks)

• Depression Symptom Improvement

  The investigators hypothesize that youth who complied with the 16-week keto diet therapy will show statistically significant reductions in depressive symptoms from baseline to completion of the diet. Depressive symptoms will primarily be captured using the clinician-rated Children's Depression Rating Scale, Revised (CDRS-R). Scores range from 17 to 113, with higher scores indicating greater pathology or severity of depressive symptoms (worse outcome).

  From initiation of ketogenic therapy to the end of treatment (up to 16 weeks)

• Bipolar Symptom Improvement

  The investigators hypothesize that youth who complied with the 16-week keto diet therapy will show statistically significant reductions in bipolar mood instability from baseline to completion of the diet. Bipolar instability will primarily be captured using the clinician-rated Clinical Global Impression - Bipolar Disorder Severity Scale (CGI-BP). CGI-BP overall psychiatric illness scores range from 1 (normal, best outcome) to 7 (very severely ill, worse outcome) and capture severity of bipolar symptoms over the worst 7-day period in the past 2 weeks.

  From initiation of ketogenic therapy to the end of treatment (up to 16 weeks)

• HOMA - IR Metabolic Indicator

  The investigators hypothesize that youth with high compliance with the keto diet will show significant pre- to post-treatment improvement in Homeostatic model assessment for insulin resistance (HOMA - IR). HOMA - IR is calculated based on fasting glucose and insulin measurements and a value greater than 2 indicates insulin resistance (worse outcome) while a value less than 1 indicates normal range insulin sensitivity (better outcome).

  From initiation of ketogenic therapy to the end of treatment (up to 16 weeks)

Secondary Outcomes (2)

• Youth Functional Improvement

  From initiation of ketogenic therapy to the end of treatment (up to 16 weeks)

• Serum Inflammatory Biomarkers (CRP)

  From initiation of ketogenic therapy to the end of treatment (up to 16 weeks)

Study Arms (1)

Ketogenic Therapy for Bipolar Spectrum Disorders

EXPERIMENTAL

This is a pilot trial with one intervention arm. All youth meeting eligibility for the ketogenic therapy phase of this pilot trial will be invited to participate in the intervention and progress tracking.

Other: Ketogenic Therapy

Interventions

Ketogenic Therapy OTHER

During the keto therapy (16 weeks), the youth will participate in a strict ketogenic diet, with adjustments made as necessary from weekly dietitian coaching sessions.

Ketogenic Therapy for Bipolar Spectrum Disorders

Eligibility Criteria

• Age: 12 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Los Angeles: lead
• University of Cincinnati: collaborator
• University of Pittsburgh: collaborator
• University of Colorado, Denver: collaborator
• Advanced Ketogenic Therapies: collaborator
• Baszucki Family Foundation: collaborator

Study Sites (4)

UCLA Semel Institute Max Gray Child and Adolescent Mood Disorders Program (CHAMP)

Los Angeles, California, 90024, United States

RECRUITING

University of Colorado Denver, Anschutz Medical Campus

Aurora, Colorado, 80045, United States

NOT YET RECRUITING

University of Cincinnati College of Medicine

Cincinnati, Ohio, 45267, United States

RECRUITING

University of Pittsburgh School of Medicine

Pittsburgh, Pennsylvania, 15213, United States

NOT YET RECRUITING

Related Publications (14)

• Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Bond DJ, Frey BN, Sharma V, Goldstein BI, Rej S, Beaulieu S, Alda M, MacQueen G, Milev RV, Ravindran A, O'Donovan C, McIntosh D, Lam RW, Vazquez G, Kapczinski F, McIntyre RS, Kozicky J, Kanba S, Lafer B, Suppes T, Calabrese JR, Vieta E, Malhi G, Post RM, Berk M. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018 Mar;20(2):97-170. doi: 10.1111/bdi.12609. Epub 2018 Mar 14.

  PMID: 29536616 BACKGROUND

• Wells J, Swaminathan A, Paseka J, Hanson C. Efficacy and Safety of a Ketogenic Diet in Children and Adolescents with Refractory Epilepsy-A Review. Nutrients. 2020 Jun 17;12(6):1809. doi: 10.3390/nu12061809.

  PMID: 32560503 BACKGROUND

• Van Meter AR, Burke C, Kowatch RA, Findling RL, Youngstrom EA. Ten-year updated meta-analysis of the clinical characteristics of pediatric mania and hypomania. Bipolar Disord. 2016 Feb;18(1):19-32. doi: 10.1111/bdi.12358. Epub 2016 Jan 9.

  PMID: 26748678 BACKGROUND

• Sondike SB, Copperman N, Jacobson MS. Effects of a low-carbohydrate diet on weight loss and cardiovascular risk factor in overweight adolescents. J Pediatr. 2003 Mar;142(3):253-8. doi: 10.1067/mpd.2003.4.

  PMID: 12640371 BACKGROUND

• Sondhi V, Agarwala A, Pandey RM, Chakrabarty B, Jauhari P, Lodha R, Toteja GS, Sharma S, Paul VK, Kossoff E, Gulati S. Efficacy of Ketogenic Diet, Modified Atkins Diet, and Low Glycemic Index Therapy Diet Among Children With Drug-Resistant Epilepsy: A Randomized Clinical Trial. JAMA Pediatr. 2020 Oct 1;174(10):944-951. doi: 10.1001/jamapediatrics.2020.2282.

  PMID: 32761191 BACKGROUND

• Sethi S, Wakeham D, Ketter T, Hooshmand F, Bjornstad J, Richards B, Westman E, Krauss RM, Saslow L. Ketogenic Diet Intervention on Metabolic and Psychiatric Health in Bipolar and Schizophrenia: A Pilot Trial. Psychiatry Res. 2024 May;335:115866. doi: 10.1016/j.psychres.2024.115866. Epub 2024 Mar 20.

  PMID: 38547601 BACKGROUND

• Miklowitz DJ, Schneck CD, Walshaw PD, Singh MK, Sullivan AE, Suddath RL, Forgey Borlik M, Sugar CA, Chang KD. Effects of Family-Focused Therapy vs Enhanced Usual Care for Symptomatic Youths at High Risk for Bipolar Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2020 May 1;77(5):455-463. doi: 10.1001/jamapsychiatry.2019.4520.

  PMID: 31940011 BACKGROUND

• Miklowitz DJ, Schneck CD, George EL, Taylor DO, Sugar CA, Birmaher B, Kowatch RA, DelBello MP, Axelson DA. Pharmacotherapy and family-focused treatment for adolescents with bipolar I and II disorders: a 2-year randomized trial. Am J Psychiatry. 2014 Jun;171(6):658-67. doi: 10.1176/appi.ajp.2014.13081130.

  PMID: 24626789 BACKGROUND

• Kossoff EH, Zupec-Kania BA, Auvin S, Ballaban-Gil KR, Christina Bergqvist AG, Blackford R, Buchhalter JR, Caraballo RH, Cross JH, Dahlin MG, Donner EJ, Guzel O, Jehle RS, Klepper J, Kang HC, Lambrechts DA, Liu YMC, Nathan JK, Nordli DR Jr, Pfeifer HH, Rho JM, Scheffer IE, Sharma S, Stafstrom CE, Thiele EA, Turner Z, Vaccarezza MM, van der Louw EJTM, Veggiotti P, Wheless JW, Wirrell EC; Charlie Foundation; Matthew's Friends; Practice Committee of the Child Neurology Society. Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open. 2018 May 21;3(2):175-192. doi: 10.1002/epi4.12225. eCollection 2018 Jun.

  PMID: 29881797 BACKGROUND

• Ildarabadi A, Mir Mohammad Ali SN, Rahmani F, Mosavari N, Pourbakhtyaran E, Rezaei N. Inflammation and oxidative stress in epileptic children: from molecular mechanisms to clinical application of ketogenic diet. Rev Neurosci. 2024 Feb 14;35(4):473-488. doi: 10.1515/revneuro-2023-0128. Print 2024 Jun 25.

  PMID: 38347675 BACKGROUND

• Gundogdu U, Gurer G, Eroglu M. Executive function, behavioral problems, and insulin resistance in adolescents with obesity. J Pediatr Endocrinol Metab. 2023 Apr 19;36(6):539-546. doi: 10.1515/jpem-2022-0510. Print 2023 Jun 27.

  PMID: 37071665 BACKGROUND

• Goldstein BI, Birmaher B, Carlson GA, DelBello MP, Findling RL, Fristad M, Kowatch RA, Miklowitz DJ, Nery FG, Perez-Algorta G, Van Meter A, Zeni CP, Correll CU, Kim HW, Wozniak J, Chang KD, Hillegers M, Youngstrom EA. The International Society for Bipolar Disorders Task Force report on pediatric bipolar disorder: Knowledge to date and directions for future research. Bipolar Disord. 2017 Nov;19(7):524-543. doi: 10.1111/bdi.12556. Epub 2017 Sep 25.

  PMID: 28944987 BACKGROUND

• Dsouza A, Haque S, Aggarwal R. The influence of ketogenic diets on mood stability in bipolar disorder. Asian J Psychiatr. 2019 Mar;41:86-87. doi: 10.1016/j.ajp.2017.10.024. Epub 2017 Oct 28. No abstract available.

  PMID: 29169915 BACKGROUND

• Batt, M., Miklowitz, D. J., Elliotte, E., Hafeman, D., Birmaher, B., Delbello, M. P., Stepanova, E., Findling, R., Goldstein, B, I., Post, R., & Schneck, C. D. (2024). A survey of expert psychiatrists regarding first- and second-line medication choices for pediatric bipolar disorder. Bipolar Disorders, 26, 119.

  BACKGROUND

Related Links

• UCLA Child Bipolar Network Research Studies Page
• Study info: U of Colorado Denver - Anschutz Medical Campus

MeSH Terms

Conditions

Bipolar Disorder

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Central Study Contacts

David J Miklowitz, Ph.D.

CONTACT

310-267-2659; dmiklowitz@mednet.ucla.edu

Danielle M Denenny, Ph.D.

CONTACT

310-825-8740; ddenenny@mednet.ucla.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: Distinguished Professor of Psychiatry

Study Record Dates

• First Submitted: March 26, 2025
• First Posted: April 10, 2025
• Study Start: March 19, 2025
• Primary Completion (Estimated): March 19, 2027
• Study Completion (Estimated): March 19, 2027
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: 2026-2029
• Access Criteria: Researchers may submit a proposal that describes planned analyses to the study PI. Once approved they will be able to access the relevant IPD, protocol and consent documents.

Locations

US (4)