FMRI of Patients Receiving IV Ketamine for Treatment Resistant Bipolar Depression

November 7, 2025 updated by: Brian Barnett

Functional Magnetic Resonance Imaging of Patients Receiving Intravenous Ketamine for Treatment Resistant Bipolar Depression

This is a prospective open-label observational study of patients with treatment resistant bipolar depression referred for intravenous ketamine, with an interventional component of fMRI.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a prospective open-label observational study of patients with treatment resistant bipolar depression referred for intravenous ketamine. All participants will receive an acute series of ketamine consisting of twice weekly infusions over three weeks. Non-responders will have their End of Study visits within 5 days of the last ketamine infusion. Responders (participants who achieve a greater than or equal to 50% decrease on their QIDS-SR-16 score from Baseline) will return for three weeks of continuation treatment (weekly ketamine) and then have their End of Study visit within 5 days of the last continuation treatment. All participants will undergo fMRI the prior to their first ketamine infusion, and after completion of their acute series.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44113
        • Cleveland Clinic Lutheran Hospital
      • Ohio City, Ohio, United States, 44113
        • Cleveland Clinic Lutheran Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Written informed consent before any study related procedures are performed
  2. Males/females at least 18 years of age but no older than 75 years of age

  3. Meet DSM-5 criteria for a current Major Depressive Episode and lifetime Bipolar I disorder or Bipolar II disorder as determined by both:

    A. a clinician's diagnostic evaluation and B. confirmed with the MINI International Neuropsychiatric Interview (MINI 7.0.2)

  4. A current depressive episode that has lasted a minimum of 4 weeks as determined by both:

    A. a clinician's diagnostic evaluation and B. confirmed with the MINI International Neuropsychiatric Interview (MINI 7.0.2)

  5. Meet all the following criteria on symptom rating scales at screening:

    A. Montgomery Asberg Depression Rating Scale (MADRS) score ≥20 B. Young Mania Rating Scale (YMRS) score of ≤ 5 C. QIDS-SR-16 score of ≥ 11

  6. Have had ≥ 2 adequate trials of mood stabilizers, antipsychotics (only those FDA approved for bipolar depression), or antidepressants or augmentation strategies during their lifetime. An adequate trial is defined as 4 weeks of medication at the minimum FDA approved dose.
  7. In the opinion of the investigator, the patient is willing and able to comply with scheduled visits, treatment plan, and other trial procedures for the duration of the study.

Exclusion Criteria:

  1. Meet DSM-5 criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder, mental retardation, or pervasive developmental disorder
  2. Meets any exclusion criteria for ketamine treatment (uncontrolled arterial hypertension, uncontrolled hyperthyroidism, severe ischemic heart disease or heart failure, severe liver or kidney disease, space occupying lesion in the brain or the spinal cord, and uncontrolled glaucoma)
  3. The patient is pregnant or breast feeding
  4. The patient has a severe medical illness or severe neurological disorder
  5. The patient has a known ketamine allergy or is taking a medication that may significantly interact with ketamine (see Appendix)
  6. Diagnosis of psychotic features during the current depressive episode or within the past 6 months
  7. Was previously enrolled in the trial
  8. Active moderate or severe substance use disorder within the last 3 months (no exclusion for tobacco use disorder of any severity)
  9. Current episode of mania/hypomania or mixed episode according to MINI or study clinician

  10. MRI contraindications

    • Severe head trauma
    • Claustrophobia incompatible with scanning
    • Cardiac pacemaker
    • Implanted cardiac defibrillator
    • Aneurysm brain clip
    • Inner ear implant
    • Prior history as a metal worker and/or certain metallic objects in the body -- must complete MRI screening form and be approved by MRI technologist before each scan
    • History of clinically significant vertigo middle ear disorder, or double vision

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Open-label Ketamine TRBD
Outpatients with treatment resistant bipolar depression referred by their clinical providers for intravenous ketamine treatment
Drug: Ketamine
Open-label Ketamine
Other: Functional magnetic resonance imaging (fMRI)
Functional magnetic resonance imaging (fMRI) of the brain

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute Response Changes in Subgenual Cingulate Functional Connectivity
Time Frame: Three weeks after treatment initiation
Seed-to-whole brain functional connectivity z-maps will be calculated from the left and right subgenual cingulate on the baseline and post-acute resting-state functional MRI (rs-fMRI) from each participant. After acute treatment, participants will be categorized as "responders" (≥50% decrease from baseline score of Quick Inventory of Depressive Symptomatology 16-item self-report, QIDS-SR-16) or "non-responders". Brain regions in responders that exhibit significantly different treatment-related change in functional connectivity compared to non-responders will be identified using general linear model methods.
Three weeks after treatment initiation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute Response Baseline Structural Connectivity
Time Frame: Three weeks after treatment initiation
Baseline structural connectivity will be assessed from baseline diffusion tensor imaging for each participant. White matter tracts in responders that exhibit significantly different mean transverse diffusivity compared to non-responders will be identified.
Three weeks after treatment initiation
Sustained Response Changes in Subgenual Cingulate Functional Connectivity
Time Frame: Six weeks after treatment initiation
Acute "responders" will undergo a maintenance treatment phase (3 treatments over 3 weeks). After maintenance treatment, participants will be categorized as "sustained responders" (≥50% decrease from baseline QIDS-SR-16 score) or "relapsers" at the end of treatment. Brain regions in sustained responders that exhibit significantly different treatment-related change in subgenual cingulate brain functional connectivity maps compared to relapsers will be identified using general linear model methods.
Six weeks after treatment initiation
Suicidal Ideation Changes in Subgenual Cingulate Functional Connectivity
Time Frame: Six weeks after treatment initiation
Brain regions in participants that experience suicidal ideation during treatment that exhibit significantly different treatment-related change in subgenual cingulate brain functional connectivity maps compared to participants who do not experience suicidal ideation will be identified using general linear model methods.
Six weeks after treatment initiation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brian Barnett

Investigators

  • Principal Investigator: Brian Barnett, MD, The Cleveland Clinic

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 12, 2024

Primary Completion (Actual)

October 31, 2025

Study Completion (Actual)

October 31, 2025

Study Registration Dates

First Submitted

September 26, 2024

First Submitted That Met QC Criteria

September 26, 2024

First Posted (Actual)

October 1, 2024

Study Record Updates

Last Update Posted (Actual)

November 10, 2025

Last Update Submitted That Met QC Criteria

November 7, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 23-1345

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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