Recruiting

Ketogenic Diet

Sponsor:

University of Pittsburgh

Code:

NCT06081426

Conditions

Bipolar Disorder

Eligibility Criteria

Sex: All

Age: 18 - 40

Healthy Volunteers: Accepted

Interventions

Non-ketogenic Diet

Ketogenic Diet

No diet

Study Details

Brief summary:

The investigators aim to examine the effect of the ketogenic diet on brain activity, metabolism, and emotions in adults with Bipolar Disorder (BD).

Conditions

Bipolar Disorder

Study ID

NCT06081426

Start date

Jan 12, 2024

Status verified date

Dec, 2025

Completion date

Jan, 2027

Anticipated

Primary completion date

Jan, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 40

Healthy Volunteers: Accepted

Inclusion Criteria:

All participants:

  • 18-40 years of age
  • Not following a ketogenic diet

BD hypomanic group (n=30):

  • Meeting sex proportion: 50% female
  • Meeting diagnosis proportion: 50:50% Bipolar I: Bipolar II (BDI:II) (Diagnostic and Statistical Manual of Mental Disorders 5; DSM-5)
  • Score greater than 10 on the Young Mania Rating Scale score(YMRS)
  • BD medications will be allowed as in our previous studies: any combination of atypical antipsychotics, lithium, antidepressants, anxiolytics (common in BD)

BD euthymic group (n=30):

  • Meeting sex proportion: 50% female
  • Meeting diagnosis proportion: 50:50% BDI:II (DSM-5)
  • Score less than or equal to 10 on YMRS
  • BD medications will be allowed as in our previous studies: any combination of atypical antipsychotics, lithium, antidepressants, anxiolytics (common in BD)

Healthy Control (HC) Group (n=30):

  • Sex matched with BD groups
  • No psychiatric history

Exclusion Criteria:

All participants:

  • Not between 18-40 years of age
  • History of head injury, neurological, pervasive developmental disorder (e.g. autism), systemic medical disease and treatment (medical records, participant report)
  • Mini-Mental State Examination score (cognitive state) <24
  • Premorbid National Adult Reading Test Intelligent Quotient (NAART IQ) estimate<85
  • Visual disturbance: <20/40 Snellen visual acuity
  • History of alcohol/substance use disorder (SUD; all substances, including nicotine), and/or illicit substance use (except cannabis) over the last 6 months (SCID-5). Note: lifetime/present cannabis use (at non-abuse (<3 times in the past month) and non SUD levels) will be allowed, given its common usage in BD and young adults. Cannabis SUD over the last 6 months will not be allowed. Urine tests on scan days will exclude current illicit substance use (except cannabis). Salivary alcohol tests on scan days will exclude intoxicated individuals
  • MRI exclusion: metallic objects, e.g., surgical implants; claustrophobia; positive pregnancy test for females or self-report pregnancy
  • Unable to understand English
  • Conditions related to the pancreas, liver, thyroid or gallbladder.
  • Taking anticoagulants and/or those with blood dyscrasias (illnesses) who have coagulation disorders (eg, hemophilia) because of the ketomojo finger stick blood tests
  • Scoring 3 or higher on positive symptom factor questions on the Positive and Negative Syndrome Scale (PANSS) questionnaire (indicative of psychotic symptoms)
  • Currently following a ketogenic diet
  • Head circumference larger than 24 inches (62cm) and/or chest circumference larger than 55 inches (139 cm)

BD hypomanic group:

  • Must be meeting sex proportions: not 50% female
  • Must be meeting diagnosis proportions: not 50:50% BDI:II (DSM-5)
  • Diagnosis of BD in a manic or euthymic episode
  • Score 10 or lower on the Young Mania Rating Scale score(YMRS)
  • Using psychotropic medications other than those allowed in inclusion criteria
  • Does not have a smartphone with a) iOS version 12.0 or above, or b) Android version 8 and later to use with the Keto-Mojo app

BD euthymic group:

  • Not meeting sex proportion: not 50% female
  • Not meeting diagnosis proportion: not 50:50% BDI:II
  • Diagnosis of BD in a depressive, hypomanic, or manic episode
  • Score greater than 10 on YMRS
  • Using psychotropic medications other than those allowed in inclusion criteria
  • Does not have a smartphone with a) iOS version 12.0 or above, or b) Android version 8 and later to use with the Keto-Mojo app

Healthy Control (HC) Group

  • Not sex-matched with BD groups
  • Has psychiatric history

Study Design

Enrollment

107 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: 1st phase Non-ketogenic Diet / 2nd phase Ketogenic Diet

Participants with Bipolar Disorder will consume a non-ketogenic diet for the first phase of the study and then a ketogenic diet for the second phase of the study

experimental: 1st phase Ketogenic Diet / 2nd phase Non-ketogenic Diet

Participants with Bipolar Disorder will consume a ketogenic diet for the first phase of the study and then a non-ketogenic diet for the second phase of the study

other: No diet

Participants without Bipolar Disorder will not participate in the diet phases of the study

Interventions

Non-ketogenic Diet

Consuming a non-ketogenic diet

Ketogenic Diet

Consuming a ketogenic diet

No diet

Participants without Bipolar Disorder will not participate in the diet phases of the study

Primary outcome measure

  • Blood oxygen level-dependent (BOLD) signal at Scan 1 [ Time Frame: Baseline Scan 1 (all participants) ]
  • Blood oxygen level-dependent (BOLD) signal at Scan 2 [ Time Frame: End of first dietary phase (8-10 weeks) (participants with Bipolar Disorder) ]
  • Blood oxygen level-dependent (BOLD) signal at Scan 3 [ Time Frame: End of second dietary phase (8-10 weeks) (participants with Bipolar Disorder) ]
  • Manic symptoms at Scan 1 [ Time Frame: Baseline Scan 1 (all participants) ]
  • Manic symptoms at Scan 2 [ Time Frame: Scan 2 at end of first dietary phase (8-10 weeks) (participants with Bipolar Disorder) ]
  • Manic symptoms at Scan 3 [ Time Frame: Scan 3 at end of second dietary phase (8-10 weeks) (participants with Bipolar Disorder) ]
  • Fasting Glucose at Baseline [ Time Frame: Baseline (all participants) ]
  • Fasting lipids at Baseline [ Time Frame: Baseline (all participants) ]
  • Fasting hepatic function panel at Baseline: total protein [ Time Frame: Baseline (all participants) ]
  • Fasting hepatic function panel at Baseline: albumin [ Time Frame: Baseline (all participants) ]
  • Fasting hepatic function panel at Baseline: bilirubin [ Time Frame: Baseline (all participants) ]
  • Fasting hepatic function panel at Baseline: liver enzyme [ Time Frame: Baseline (all participants) ]
  • Fasting Glucose at halfway point through first dietary phase [ Time Frame: Halfway point through first dietary phase (4-5 weeks) (participants with Bipolar Disorder) ]
  • Fasting lipids at halfway point through first dietary phase [ Time Frame: Halfway point through first dietary phase (4-5 weeks) (participants with Bipolar Disorder) ]
  • Fasting hepatic function at halfway point through first dietary phase: total protein [ Time Frame: Halfway point through first dietary phase (4-5 weeks) (participants with Bipolar Disorder) ]
  • Fasting hepatic function at halfway point through first dietary phase: albumin [ Time Frame: Halfway point through first dietary phase (4-5 weeks) (participants with Bipolar Disorder) ]
  • Fasting hepatic function at halfway point through first dietary phase: bilirubin [ Time Frame: Halfway point through first dietary phase (4-5 weeks) (participants with Bipolar Disorder) ]
  • Fasting hepatic function at halfway point through first dietary phase: liver enzyme [ Time Frame: Halfway point through first dietary phase (4-5 weeks) (participants with Bipolar Disorder) ]
  • Fasting Glucose at end of first dietary phase [ Time Frame: End of first dietary phase (8-10 weeks) (participants with Bipolar Disorder) ]
  • Fasting lipids at end of first dietary phase [ Time Frame: End of first dietary phase (8-10 weeks) (participants with Bipolar Disorder) ]
  • Fasting hepatic function at end of first dietary phase: total protein [ Time Frame: End of first dietary phase (8-10 weeks) (participants with Bipolar Disorder) ]
  • Fasting hepatic function at end of first dietary phase: albumin [ Time Frame: End of first dietary phase (8-10 weeks) (participants with Bipolar Disorder) ]
  • Fasting hepatic function at end of first dietary phase: bilirubin [ Time Frame: End of first dietary phase (8-10 weeks) (participants with Bipolar Disorder) ]
  • Fasting hepatic function at end of first dietary phase: liver enzyme [ Time Frame: End of first dietary phase (8-10 weeks) (participants with Bipolar Disorder) ]
  • Fasting Glucose at halfway point through second dietary phase [ Time Frame: Halfway point through second dietary phase (4-5 weeks) (participants with Bipolar Disorder) ]
  • Fasting lipids at halfway point through second dietary phase [ Time Frame: Halfway point through second dietary phase (4-5 weeks) (participants with Bipolar Disorder) ]
  • Fasting hepatic function at halfway point through second dietary phase: total protein [ Time Frame: Halfway point through second dietary phase (4-5 weeks) (participants with Bipolar Disorder) ]
  • Fasting hepatic function at halfway point through second dietary phase: albumin [ Time Frame: Halfway point through second dietary phase (4-5 weeks) (participants with Bipolar Disorder) ]
  • Fasting hepatic function at halfway point through second dietary phase: bilirubin [ Time Frame: Halfway point through second dietary phase (4-5 weeks) (participants with Bipolar Disorder) ]
  • Fasting hepatic function at halfway point through second dietary phase: liver enzyme [ Time Frame: Halfway point through second dietary phase (4-5 weeks) (participants with Bipolar Disorder) ]
  • Fasting Glucose at end of second dietary phase [ Time Frame: End of second dietary phase (8-10 weeks) (participants with Bipolar Disorder) ]
  • Fasting lipids at end of second dietary phase [ Time Frame: End of second dietary phase (8-10 weeks) (participants with Bipolar Disorder) ]
  • Fasting hepatic function at end of second dietary phase: total protein [ Time Frame: End of second dietary phase (8-10 weeks) (participants with Bipolar Disorder) ]
  • Fasting hepatic function at end of second dietary phase: albumin [ Time Frame: End of second dietary phase (8-10 weeks) (participants with Bipolar Disorder) ]
  • Fasting hepatic function at end of second dietary phase: bilirubin [ Time Frame: End of second dietary phase (8-10 weeks) (participants with Bipolar Disorder) ]
  • Fasting hepatic function at end of second dietary phase: liver enzyme [ Time Frame: End of second dietary phase (8-10 weeks) (participants with Bipolar Disorder) ]
  • Gamma-aminobutyric acid (GABA) at Baseline [ Time Frame: Baseline Scan 1 (all participants) ]
  • Glutamate at Baseline [ Time Frame: Baseline Scan 1 (all participants) ]
  • Lactate at Baseline [ Time Frame: Baseline Scan 1 (all participants) ]
  • Gamma-aminobutyric acid (GABA) at end of first dietary phase [ Time Frame: Scan 2 at end of first dietary phase (8-10 weeks) (participants with Bipolar Disorder) ]
  • Glutamate at end of first dietary phase [ Time Frame: Scan 2 at end of first dietary phase (8-10 weeks) (participants with Bipolar Disorder) ]
  • Lactate at end of first dietary phase [ Time Frame: Scan 2 at end of first dietary phase (8-10 weeks) (participants with Bipolar Disorder) ]
  • Gamma-aminobutyric acid (GABA) at end of second dietary phase [ Time Frame: Scan 3 at end of second dietary phase (8-10 weeks) (participants with Bipolar Disorder) ]
  • Glutamate at end of second dietary phase [ Time Frame: Scan 3 at end of second dietary phase (8-10 weeks) (participants with Bipolar Disorder) ]
  • Lactate at end of second dietary phase [ Time Frame: Scan 3 at end of second dietary phase (8-10 weeks) (participants with Bipolar Disorder) ]

Central Contacts and Locations

Central contacts

Jill Morris-Tillman

412-383-8206morristillmanje@upmc.edu

Locations

University of Pittsburgh Medical Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15213

Contacts

Jill Morris-Tillman

412-383-8206morristillmanje@upmc.edu

Principal Investigator:

Mary L Phillps, MD, MD

More Information

Sponsor

University of Pittsburgh

Last update posted

Dec 10, 2025

Last verified

Dec, 2025

Keywords

  • Ketogenic Diet
  • Magnetic Resonance Imaging

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Pittsburgh on 2025-12-10.