NCT06373016 · Stony Brook University
Use of Ketosis in Modulating Metabolic Pathways in Bipolar Disorder
What this study is about
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.
View original scientific description
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.
Interventions
DIETARY_SUPPLEMENT
Glucose
A glucose drink is administered midway through one of the scan sessions.
DIETARY_SUPPLEMENT
Ketones
A ketone drink is administered midway through one of the scan sessions.
Primary outcome measures
Stabilization of brain networks (general brain functioning)
Time frame: Within a month of enrollment completion
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.
Relative stabilization or destabilization of brain networks in response to metabolic bolus
Time frame: Within a month of enrollment completion
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.
Prefrontal-limbic circuit regulation
Time frame: Within a month of enrollment completion
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.
Cortico-striatal circuit regulation
Time frame: Within a month of enrollment completion
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.
Concentration of neurometabolites measured by Magnetic Resonance Spectroscopy (MRS)
Time frame: Within a month of enrollment completion
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
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Exclusion criteria
- 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
- No current diagnosis or history of an alcohol or substance use disorder in the last 6 months or positive test for an illicit drug on the screening urine analysis (positive cannabis screen is not exclusionary): confirmed using urine toxicology test during the initial screening visit and before each MRI scan visit.
- For Healthy Volunteers Only: No psychotropic medication and no history of neurological disease
- Must have vision that is 20/20 or correctable to 20/20 with contact lenses
- No Type 1 diabetes mellitus
- No regular consumption of insulin and other antidiabetics, like Metformin®, GLP1-RA's and others.
- No kidney disease, as determined by medical history and/or blood work
- No history of heart attack or stroke
- No difficulty swallowing
- No myxedema
- No Pregnancy (pre-menopausal females): confirmed during medical screening and each MRI scan visit using a urine test
- No breastfeeding
Where
- Belmont, Massachusetts
- Charlestown, Massachusetts
- Stony Brook, New York
Collaborators
Massachusetts General Hospital, Mclean Hospital
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Apr 15, 2026 · Source of record for eligibility and locations