Use of Ketosis in Modulating Metabolic Pathways in Bipolar Disorder

NCT ID: NCT06373016

Last Updated: 2024-04-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-26
• Study Completion Date: 2027-02-01

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.

Detailed Description

The purpose of the study is to understand the impact of glucose vs. ketones on brain metabolism and function, in individuals with bipolar. The specific aims are to examine:

1. Stability of the brain's signaling over time.

2. Regulation of the neural circuits that process risk

3. Regulation of the neural circuits that process reward

Study Procedures:

Baseline Blood Samples: Blood will be taken at Massachusetts General Hospital (Translational and Clinical Research Center) to measure baseline levels of several key variables associated with metabolic function. These variables include insulin resistance (HbA1c), thyroid function (T3, T4, TSH), the efficiency of the tricarboxylic acid (TCA) cycle (lactate/pyruvate), energy sensing (AMPK), mitochondrial regulation, and inflammation (IL-6, tumor necrosis factor (TNF)-alpha).

Scanning Procedure: The scanning procedure for magnetic resonance (MR) imaging, on each day, will include 1) functional MR (fMRI) during cognitive task (three games), 2) MR spectroscopy (MRS), and 3) resting state. Following the scan, the participant will drink either glucose or ketones and repeat 1-3 above.

Blood glucose and ketone monitoring: Using a finger-prick test, investigators will measure blood glucose and ketones three times during each scan session. This will be done immediately before starting the scan session, 10 minutes after consuming either glucose or ketones, and immediately after ending the scan session. Mild temporary pain/discomfort may occur at the site of finger-prick for blood glucose and ketone concentration measurements (pre-scan, post-drink, and post-scan), but no other side effects are expected from this test. Precision Xtra is a standard over-the-counter blood glucose and ketone monitoring system routinely self-administered by diabetic patients. Participants' fingers will be sanitized with alcohol wipes and a fresh lancet will be used to perform each finger prick test.

Conditions

Bipolar Disorder; Bipolar Disorder Type 1

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Ketone Supplement-MRI/MRS

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.

Group Type: EXPERIMENTAL

Glucose

Intervention Type: DIETARY_SUPPLEMENT

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

Ketones

Intervention Type: DIETARY_SUPPLEMENT

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

Interventions

Glucose

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

Intervention Type: DIETARY_SUPPLEMENT

Ketones

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

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Mclean Hospital

OTHER

Sponsor Role: collaborator

Stony Brook University

OTHER

Sponsor Role: lead

Responsible Party

Lilianne Strey

Professor, Department of Biomedical Engineering

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lilianne R Mujica-Parodi, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

SUNY Stony Brook University

Locations

McLean Hospital

Belmont, Massachusetts, United States

Site Status: RECRUITING

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

Charlestown, Massachusetts, United States

Site Status: RECRUITING

Laufer Center for Physical and Quantitative Biology , Stony Brook University

Stony Brook, New York, United States

Site Status: ACTIVE_NOT_RECRUITING

Countries

United States

Central Contacts

Annabel Driussi, MA

Role: CONTACT

annabel.driussi@stonybrook.edu

510-333-6732

Janaki Raghavan, PhD

Role: CONTACT

janaki.raghavan@stonybrook.edu

774-479-2660

Facility Contacts

Dost Ongur, MD PhD

Role: primary

dongur@mgb.org

617-855-3922

Virginie-Anne Chouinard, MD

Role: backup

vchouinard@mgb.org

617-855-3034

Lilianne Mujica-Parodi, PhD

Role: primary

lstrey@mgh.harvard.edu

631-428-8461

Eva-Maria Ratai, PhD

Role: backup

eratai@mgh.harvard.edu

781-521-4436

Related Links

https://www.lcneuro.org

Laboratory for Computational Neurodiagnostics

Other Identifiers

2023005

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2015P000652

Identifier Type: -

Identifier Source: org_study_id