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.
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
- Are there results?
- None posted in the registry
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
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.
- 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 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.
- 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)
Sponsor and investigators
- Lead sponsor
- Drew Cumming
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Drew Cumming, The Cleveland Clinic
- Investigators
- Brian Barnett, MD, Principal investigator, The Cleveland Clinic
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
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Functional Magnetic Resonance Imaging of Patients Receiving Intravenous Ketamine for Treatment Resistant Bipolar Depression
- ClinicalTrials.gov ID
- NCT06620042
- Acronym / sponsor ID
- 23-1345
- Keywords
- ketamine, bipolar depression, bipolar disorder, bipolar
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Drew CummingUniversity, hospital or other
- Study start
- 12 Nov 2024 (actual)
- Primary completion
- 31 Oct 2025 (actual)
- Study completion
- 31 Oct 2025 (actual)
- First posted
- 1 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Open-label Ketamine TRBD | Other | Drug: Ketamine, Other: Functional magnetic resonance imaging (fMRI)Outpatients with treatment resistant bipolar depression referred by their clinical providers for intravenous ketamine treatment |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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 current depressive episode that has lasted a minimum of 4 weeks as determined by both:
- Meet all the following criteria on symptom rating scales at screening:
Key exclusion criteria (18 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetamineOpen-label Ketamine | Drug | Open-label Ketamine TRBD |
| Functional magnetic resonance imaging (fMRI)Functional magnetic resonance imaging (fMRI) of the brain | Other | Open-label Ketamine TRBD |
Primary outcome
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.
3 secondary outcomes
Acute Response Baseline Structural Connectivity
Time frame: Three weeks after treatment initiation
Sustained Response Changes in Subgenual Cingulate Functional Connectivity
Time frame: Six weeks after treatment initiation
Suicidal Ideation Changes in Subgenual Cingulate Functional Connectivity
Time frame: Six weeks after treatment initiation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian Barnett, MD principal investigator
The Cleveland Clinic
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acute Response Changes in Subgenual Cingulate Functional Connectivity (time frame: Three weeks after treatment initiation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.