Use of Ketosis in Modulating Metabolic Pathways in Bipolar Disorder

NCT06373016 | Recruiting

• 2 other identifiers: 2015P0006522023005
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this clinical trial is to test how specific components of diet affect brain function and behavior for individuals with bipolar. The main question it aims to answer is how glucose and ketones each affect the brain's response to risk and reward. Participants will be asked to provide blood (to assess baseline measures of how the body uses energy), and then to receive two MRI scan sessions, on separate days. During each MRI scan session, participants will play three games, from which they can win money, before and after drinking glucose (on one day) or ketones (on the other day). Investigators will compare individuals with and without bipolar to test whether the two groups differ in how their brains use energy, and to test how the brain's use of energy affects behavior.

Conditions

Bipolar Disorder; Bipolar Disorder Type 1

Outcome Measures

Primary Outcomes (5)

• Stabilization of brain networks (general brain functioning)

  Baseline network stability will be measured using resting-state fMRI. Brain network stability (unitless metric) is a biomarker derived from fMRI scan activity that quantifies the degree to which regions that are active together at one time point continue to remain active together throughout the scan. It has been shown by prior work to be a biomarker sensitive to both aging and metabolic effects and is thus a primary measure as this study examines its validity in the context of bipolar disorder. Given this prior work, it is anticipated that relative to comparison subjects, individuals with bipolar disorder will show greater network instability (increased instability score - unitless) consistent with metabolic dysregulation.

  Within a month of enrollment completion

• Relative stabilization or destabilization of brain networks in response to metabolic bolus

  Using the resting-state fMRI acquired after either the glucose or ketone bolus, brain network stability will be quantified as described above and compared to the baseline outcome. Based on prior work using this metric, it is anticipated that in both healthy individuals and individuals with bipolar disorder will exhibit network stabilization in the presence of ketones (decreased instability score - unitless) and network destabilization in the presence of glucose (increased instability score - unitless), consistent with the effects seen in metabolic regulation in an aging population.

  Within a month of enrollment completion

• Prefrontal-limbic circuit regulation

  Using task fMRI data for learning and matching tasks, the BOLD signal will be measured for the pre-frontal limbic circuit (composed of the ventromedial prefrontal cortex, orbitofrontal cortex, hippocampus, amygdala, and thalamus). The relative signal correlations between these regions will be used to determine signal lag (measured in seconds) as a metric of circuit regulation. Prior work has shown this metric to be sensitive to changes in emotional regulation (specifically in generalized anxiety disorder), and thus it is hypothesized to provide a sensitive marker in comparing individuals with bipolar disorder to healthy individuals as well.

  Within a month of enrollment completion

• Cortico-striatal circuit regulation

  Using task fMRI data for learning and matching tasks, the BOLD signal will be measured for the cortico-striatal circuit (composed of the prefrontal cortex, striatum, thalamus, globus pallidus, subthalamic nucleus, and substantia nigra). The relative signal correlations between these regions will be used to determine signal lag (measured in seconds) as a metric of circuit regulation. Prior work has shown this circuit to be important in learning tasks like the ones used in this study, and thus provides an excellent control circuit for comparison to the pre-frontal limbic metrics above.

  Within a month of enrollment completion

• Concentration of neurometabolites measured by Magnetic Resonance Spectroscopy (MRS)

  Using 7T MRS allows us to sensitively measure the concentrations of several neurometabolites sensitively and simultaneously. The following metabolite concentrations (in mmol) will be quantified both before and after the energy bolus consumption: Neural glucose and D-βHB (ketone), Taurine, Lactate, Ascorbate, Phosphocreatine, Aspartate, Phosphoethanolamine, Gamma-Aminobutyric Acid (GABA), Scyllo-Inositol, Myo-Inositol, Phosphocholine and Glycerophosphocholine, Glutathione, N-Acetylaspartate, Creatine and Phosphocreatine, N-Acetylaspartate and N-Acetylaspartylglutamate, Glutamate, Glutamine, N-Acetylaspartylglutamate

  Within a month of enrollment completion

Study Arms (1)

Ketone Supplement-MRI/MRS

EXPERIMENTAL

Participants (both the Bipolar Cohort and Healthy Comparison Cohort) will be tested twice, both times in an overnight fasting condition (8 hours no food, unrestricted water). Halfway through each of the two scan sessions, participants will be asked to drink either glucose (on one day) or ketones (on the other day). This within-subjects comparison will allow investigators to observe the effects of metabolism on brain function. Participants' glucose and ketone levels will also be measured, using a finger-prick blood measurement at three different times: 1) immediately before the scan session 2) 10 minutes after drinking the glucose or supplement 3) immediately following the scan session.

Dietary Supplement: Glucose; Dietary Supplement: Ketones

Interventions

Glucose DIETARY_SUPPLEMENT

A glucose drink is administered midway through one of the scan sessions.

Ketone Supplement-MRI/MRS

Ketones DIETARY_SUPPLEMENT

A ketone drink is administered midway through one of the scan sessions.

Ketone Supplement-MRI/MRS

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• Bipolar disorder diagnosis: Patients must have a Diagnostic Statistical Manual (DSM)-V diagnosis of bipolar disorder on the Structured Clinical Interview for DSM (SCID)
• Bipolar disorder symptoms: Patients must be stable and euthymic at time of consent and testing, documented by no hospitalizations in the prior 4 weeks
• Age: between 18-45 yrs for patients with bipolar disorder and age-matched controls
• Weight does not exceed 350lbs.
• Diameter does not exceed 60 cm when supine
• HbA1C \< 7%
• No non-MRI-compatible metal in the body (e.g., pacemaker, shrapnel, joint pins)
• No claustrophobia
• No history of significant head injury
• No history of electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) within the last 3 months
• No history of previous treatment with following procedures: vagus nerve stimulation, or deep brain stimulation
• Are not deemed a serious suicide or homicide risk
• No unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease
• No seizure disorders
• Have the capacity to sign informed consent

Sponsors & Collaborators

• Stony Brook University: lead
• Massachusetts General Hospital: collaborator
• Mclean Hospital: collaborator

Study Sites (3)

McLean Hospital

Belmont, Massachusetts, 02478, United States

RECRUITING

Martinos Center for Biomedical Research, Building 149, 13th Street

Charlestown, Massachusetts, 02129, United States

RECRUITING

Laufer Center for Physical and Quantitative Biology , Stony Brook University

Stony Brook, New York, 11794, United States

ACTIVE NOT RECRUITING

Related Links

• Laboratory for Computational Neurodiagnostics

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Glucose; Ketones

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates; Organic Chemicals

Study Officials

• Lilianne R Mujica-Parodi, Ph.D.

  SUNY Stony Brook University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephen Burke, BS

CONTACT

914-325-0868; stephen.j.burke@stonybrook.edu

Sadia Jumana, BS

CONTACT

339-241-2515; sadiaanjum.jumana@stonybrook.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Biomedical Engineering

Study Record Dates

• First Submitted: February 7, 2024
• First Posted: April 18, 2024
• Study Start: January 26, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (3)