Examining Neurobiological Mechanisms Underlying the Therapeutic Effect of the Ketogenic Diet in Bipolar Disorder (BD)

NCT06081426 | Recruiting

• 1 other identifier: STUDY23080048
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 1

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

Keywords

Ketogenic Diet; Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (45)

• Blood oxygen level-dependent (BOLD) signal at Scan 1

  The blood oxygen level-dependent (BOLD) signal indicates brain activity and connectivity

  Baseline Scan 1 (all participants)

• Blood oxygen level-dependent (BOLD) signal at Scan 2

  The blood oxygen level-dependent (BOLD) signal indicates brain activity and connectivity

  End of first dietary phase (8-10 weeks) (participants with Bipolar Disorder)

• Blood oxygen level-dependent (BOLD) signal at Scan 3

  The blood oxygen level-dependent (BOLD) signal indicates brain activity and connectivity

  End of second dietary phase (8-10 weeks) (participants with Bipolar Disorder)

• Manic symptoms at Scan 1

  The Young Mania Rating Scale (YMRS) indicates the level of manic symptoms with a total score that varies between zero (better outcome) and 60 (worse outcome)

  Baseline Scan 1 (all participants)

• Manic symptoms at Scan 2

  The Young Mania Rating Scale (YMRS) indicates the level of manic symptoms with a total score that varies between zero (better outcome) and 60 (worse outcome)

  Scan 2 at end of first dietary phase (8-10 weeks) (participants with Bipolar Disorder)

• Manic symptoms at Scan 3

  The Young Mania Rating Scale (YMRS) indicates the level of manic symptoms with a total score that varies between zero (better outcome) and 60 (worse outcome)

  Scan 3 at end of second dietary phase (8-10 weeks) (participants with Bipolar Disorder)

• Fasting Glucose at Baseline

  Fasting glucose blood levels

  Baseline (all participants)

• Fasting lipids at Baseline

  Fasting lipid blood levels

  Baseline (all participants)

• Fasting hepatic function panel at Baseline: total protein

  Fasting levels of total protein in the blood

  Baseline (all participants)

• Fasting hepatic function panel at Baseline: albumin

  Fasting levels of albumin in the blood

  Baseline (all participants)

• Fasting hepatic function panel at Baseline: bilirubin

  Fasting levels of bilirubin in the blood

  Baseline (all participants)

• Fasting hepatic function panel at Baseline: liver enzyme

  Fasting levels of liver enzyme in the blood

  Baseline (all participants)

• Fasting Glucose at halfway point through first dietary phase

  Fasting glucose blood levels

  Halfway point through first dietary phase (4-5 weeks) (participants with Bipolar Disorder)

• Fasting lipids at halfway point through first dietary phase

  Fasting lipid blood levels

  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

  Fasting levels of total protein in the blood

  Halfway point through first dietary phase (4-5 weeks) (participants with Bipolar Disorder)

• Fasting hepatic function at halfway point through first dietary phase: albumin

  Fasting levels of albumin in the blood

  Halfway point through first dietary phase (4-5 weeks) (participants with Bipolar Disorder)

• Fasting hepatic function at halfway point through first dietary phase: bilirubin

  Fasting levels of bilirubin in the blood

  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

  Fasting levels of liver enzyme in the blood

  Halfway point through first dietary phase (4-5 weeks) (participants with Bipolar Disorder)

• Fasting Glucose at end of first dietary phase

  Fasting glucose blood levels

  End of first dietary phase (8-10 weeks) (participants with Bipolar Disorder)

• Fasting lipids at end of first dietary phase

  Fasting lipid blood levels

  End of first dietary phase (8-10 weeks) (participants with Bipolar Disorder)

• Fasting hepatic function at end of first dietary phase: total protein

  Fasting levels of total protein in the blood

  End of first dietary phase (8-10 weeks) (participants with Bipolar Disorder)

• Fasting hepatic function at end of first dietary phase: albumin

  Fasting levels of albumin in the blood

  End of first dietary phase (8-10 weeks) (participants with Bipolar Disorder)

• Fasting hepatic function at end of first dietary phase: bilirubin

  Fasting levels of bilirubin in the blood

  End of first dietary phase (8-10 weeks) (participants with Bipolar Disorder)

• Fasting hepatic function at end of first dietary phase: liver enzyme

  Fasting levels of liver enzyme in the blood

  End of first dietary phase (8-10 weeks) (participants with Bipolar Disorder)

• Fasting Glucose at halfway point through second dietary phase

  Fasting glucose blood levels

  Halfway point through second dietary phase (4-5 weeks) (participants with Bipolar Disorder)

• Fasting lipids at halfway point through second dietary phase

  Fasting lipid blood levels

  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

  Fasting levels of total protein in the blood

  Halfway point through second dietary phase (4-5 weeks) (participants with Bipolar Disorder)

• Fasting hepatic function at halfway point through second dietary phase: albumin

  Fasting levels of albumin in the blood

  Halfway point through second dietary phase (4-5 weeks) (participants with Bipolar Disorder)

• Fasting hepatic function at halfway point through second dietary phase: bilirubin

  Fasting levels of bilirubin in the blood

  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

  Fasting levels of liver enzyme in the blood

  Halfway point through second dietary phase (4-5 weeks) (participants with Bipolar Disorder)

• Fasting Glucose at end of second dietary phase

  Fasting glucose blood levels

  End of second dietary phase (8-10 weeks) (participants with Bipolar Disorder)

• Fasting lipids at end of second dietary phase

  Fasting lipids blood levels

  End of second dietary phase (8-10 weeks) (participants with Bipolar Disorder)

• Fasting hepatic function at end of second dietary phase: total protein

  Fasting levels of total protein in the blood

  End of second dietary phase (8-10 weeks) (participants with Bipolar Disorder)

• Fasting hepatic function at end of second dietary phase: albumin

  Fasting levels of albumin in the blood

  End of second dietary phase (8-10 weeks) (participants with Bipolar Disorder)

• Fasting hepatic function at end of second dietary phase: bilirubin

  Fasting levels of bilirubin in the blood

  End of second dietary phase (8-10 weeks) (participants with Bipolar Disorder)

• Fasting hepatic function at end of second dietary phase: liver enzyme

  Fasting levels of liver enzyme in the blood

  End of second dietary phase (8-10 weeks) (participants with Bipolar Disorder)

• Gamma-aminobutyric acid (GABA) at Baseline

  Gamma-aminobutyric acid (GABA) concentrations in the brain

  Baseline Scan 1 (all participants)

• Glutamate at Baseline

  Glutamate concentrations in the brain

  Baseline Scan 1 (all participants)

• Lactate at Baseline

  Lactate concentrations in the brain

  Baseline Scan 1 (all participants)

• Gamma-aminobutyric acid (GABA) at end of first dietary phase

  Gamma-aminobutyric acid (GABA) concentrations in the brain

  Scan 2 at end of first dietary phase (8-10 weeks) (participants with Bipolar Disorder)

• Glutamate at end of first dietary phase

  Glutamate concentrations in the brain

  Scan 2 at end of first dietary phase (8-10 weeks) (participants with Bipolar Disorder)

• Lactate at end of first dietary phase

  Lactate concentrations in the brain

  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

  Gamma-aminobutyric acid (GABA) concentrations in the brain

  Scan 3 at end of second dietary phase (8-10 weeks) (participants with Bipolar Disorder)

• Glutamate at end of second dietary phase

  Glutamate concentrations in the brain

  Scan 3 at end of second dietary phase (8-10 weeks) (participants with Bipolar Disorder)

• Lactate at end of second dietary phase

  Lactate concentrations in the brain

  Scan 3 at end of second dietary phase (8-10 weeks) (participants with Bipolar Disorder)

Secondary Outcomes (8)

• Average total sleep time during Ketogenic vs Normal diet

  Wrist actigraphy will be collected throughout the 8-10wk ketogenic diet and normal diet study intervals

• Average rest-activity rhythm interdaily stability during Ketogenic vs Normal diet

  Wrist actigraphy will be collected throughout the 8-10 wk ketogenic diet and normal diet study intervals.

• Ecological momentary assessments (EMA) during the first dietary phase: Mood monitoring

  The first dietary phase (8-10 weeks) (participants with Bipolar Disorder)

• Ecological momentary assessments (EMA) during the first dietary phase: Energy monitoring

  The first dietary phase (8-10 weeks) (participants with Bipolar Disorder)

• Ecological momentary assessments (EMA) during the first dietary phase: Suicidality monitoring

  The first dietary phase (8-10 weeks) (participants with Bipolar Disorder)

Study Arms (3)

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

EXPERIMENTAL

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

Other: Non-ketogenic Diet; Other: Ketogenic Diet

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

EXPERIMENTAL

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: Non-ketogenic Diet; Other: Ketogenic Diet

No diet

OTHER

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

Other: No diet

Interventions

Non-ketogenic Diet OTHER

Consuming a non-ketogenic diet

1st phase Ketogenic Diet / 2nd phase Non-ketogenic Diet; 1st phase Non-ketogenic Diet / 2nd phase Ketogenic Diet

Ketogenic Diet OTHER

Consuming a ketogenic diet

1st phase Ketogenic Diet / 2nd phase Non-ketogenic Diet; 1st phase Non-ketogenic Diet / 2nd phase Ketogenic Diet

No diet OTHER

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

No diet

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• All participants:
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Pittsburgh: lead
• Baszucki Brain Research Fund: collaborator

Study Sites (1)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Diet, Ketogenic

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Mary Phillips, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jill Morris-Tillman

CONTACT

412-383-8206; morristillmanje@upmc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 22, 2023
• First Posted: October 13, 2023
• Study Start: January 12, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: December 10, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: The principal investigators (PIs) reserve the right to publish on the stated aims in a timely manner. Data will be available for addressing other research questions (i.e. which are not described in funded/pending grants) as soon as the data have been checked for accuracy (a period which will be no later than one year after the completion of each assessment). After the study has ended, the study investigators will continue to test the stated aims, but will also continue to solicit collaborations with outside researchers and to consider data requests in a timely manner.
• Access Criteria: Outside investigators must submit a 1)proposal of the study aims, hypotheses, variables/constructs, analytic approach, and estimated duration of the proposed research; 2)resume, qualifications, source of financial support, and conflict of interest statement; 3)sign a data-sharing agreement and confidentiality statement that stipulates using the data for the stated research purposes only, securing the data using appropriate computer technology, not manipulating the data in order to identify participants, acknowledging the grant that supported data collection and management in publications/presentations, and destroying or returning the data after analyses are complete; 4)obtain approval from their Institutional Review Board, and along with other staff members who have access to the data, submit certificates of the University of Pittsburgh Education and Certification Program in Research Practice Fundamentals or provide written documentation of similar human subjects protection training.

Locations

US (1)