FMRI of Patients Receiving IV Ketamine for Treatment Resistant Bipolar Depression

NCT06620042 | Completed Phase 2 FDA Drug

• 1 other identifier: 23-1345
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Bipolar Depression; Treatment Resistant Bipolar Depression

Keywords

ketamine; bipolar depression; bipolar disorder; bipolar

Outcome Measures

Primary Outcomes (1)

• Acute Response Changes in Subgenual Cingulate Functional Connectivity

  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 Outcomes (3)

• Acute Response Baseline Structural Connectivity

  Three weeks after treatment initiation

• Sustained Response Changes in Subgenual Cingulate Functional Connectivity

  Six weeks after treatment initiation

• Suicidal Ideation Changes in Subgenual Cingulate Functional Connectivity

  Six weeks after treatment initiation

Study Arms (1)

Open-label Ketamine TRBD

OTHER

Outpatients with treatment resistant bipolar depression referred by their clinical providers for intravenous ketamine treatment

Drug: Ketamine; Other: Functional magnetic resonance imaging (fMRI)

Interventions

Ketamine DRUG

Open-label Ketamine

Open-label Ketamine TRBD

Functional magnetic resonance imaging (fMRI) OTHER

Functional magnetic resonance imaging (fMRI) of the brain

Open-label Ketamine TRBD

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Meet DSM-5 criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder, mental retardation, or pervasive developmental disorder
• The patient is pregnant or breast feeding
• The patient has a severe medical illness or severe neurological disorder
• The patient has a known ketamine allergy or is taking a medication that may significantly interact with ketamine (see Appendix)
• Diagnosis of psychotic features during the current depressive episode or within the past 6 months
• Was previously enrolled in the trial
• Current episode of mania/hypomania or mixed episode according to MINI or study clinician
• 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

Sponsors & Collaborators

• Brian Barnett: lead

Study Sites (2)

Cleveland Clinic Lutheran Hospital

Cleveland, Ohio, 44113, United States

Location

Cleveland Clinic Lutheran Hospital

Ohio City, Ohio, 44113, United States

Location

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Brian Barnett, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Staff Physician

Model Details: 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. 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 ≥ 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 prior to their first ketamine infusion and after completion of their acute series.

Study Record Dates

• First Submitted: September 26, 2024
• First Posted: October 1, 2024
• Study Start: November 12, 2024
• Primary Completion: October 31, 2025
• Study Completion: October 31, 2025
• Last Updated: November 10, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)