Bipolar DepressionPhase 2NCT06620042

FMRI of Patients Receiving IV Ketamine for Treatment Resistant Bipolar Depression

A Phase 2 study testing Ketamine and Functional magnetic resonance imaging (fMRI) in people with Bipolar Depression and Treatment Resistant Bipolar Depression, run by Drew Cumming at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Bipolar Depression, Treatment Resistant Bipolar Depression
What is being tested?: Ketamine and Functional magnetic resonance imaging (fMRI)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 20 participants
Where: 2 sitesUnited States
Study dates: 12 Nov 2024to 31 Oct 2025
Phase: Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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

Who cannot join

Meet DSM-5 criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder, mental retardation, or pervasive developmental disorder
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)
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

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Was previously enrolled in the trial
Active moderate or severe substance use disorder within the last 3 months (no exclusion for tobacco use disorder of any severity)
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
History of clinically significant vertigo middle ear disorder, or double vision

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Cleveland Clinic Lutheran Hospital
Cleveland, Ohio, 44113
Cleveland Clinic Lutheran Hospital
Ohio City, Ohio, 44113

Other trials in United States

About this study

Official title: 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.

Read the 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.

Conditions: Bipolar Depression, Treatment Resistant Bipolar Depression
Being tested: Ketamine, Functional magnetic resonance imaging (fMRI)
Keywords: ketamine, bipolar depression, bipolar disorder, bipolar
Medical subject headings: Bipolar Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

KetamineDrug
Open-label Ketamine
Functional magnetic resonance imaging (fMRI)Other
Functional magnetic resonance imaging (fMRI) of the brain

Study groups in NCT06620042
Study group	Role	What they receive
Open-label Ketamine TRBD	Other	Outpatients with treatment resistant bipolar depression referred by their clinical providers for intravenous ketamine treatment Receives: Drug: Ketamine; Other: Functional magnetic resonance imaging (fMRI)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Three weeks after treatment initiation

Secondary outcomes (3)

Acute Response Baseline Structural Connectivity
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.
Measured: Three weeks after treatment initiation
Sustained Response Changes in Subgenual Cingulate Functional Connectivity
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.
Measured: Six weeks after treatment initiation
Suicidal Ideation Changes in Subgenual Cingulate Functional Connectivity
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.
Measured: Six weeks after treatment initiation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Nov 202431 Oct 2025

First posted1 Oct 2024
Study start12 Nov 2024
Primary completion31 Oct 2025
Study completion31 Oct 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Bipolar DepressionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Model description: 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.
Masking: None (open label)
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06620042
Sponsor's protocol ID: 23-1345
Status last verified: Oct 2026
First submitted: 26 Sep 2024
Last updated: 15 Oct 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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