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Bipolar DisorderPhase 2KET-BD-SustainNCT05339074

Maintenance Ketamine Infusions for Treatment-Resistant Bipolar Depression

A Phase 2 study testing Ketamine Hydrochloride in people with Bipolar Disorder and Bipolar Depression, run by Joshua Rosenblat at 3 sites in Canada.

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

Growing evidence has supported rapid and robust antidepressant effects with subanesthetic doses of intravenous (IV) ketamine for treatment resistant depression (TRD). However, no completed or ongoing RCTs have evaluated the effects of repeated doses of IV ketamine for a homogenous sample of patients with… Read more about this study

Who is it for?
Ages 21 to 65 years
What is being tested?
Ketamine Hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
3 sitesCanada
Study dates
11 Aug 2022to 28 Jan 2026
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 21 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Provide written, voluntary informed consent prior to study enrollment. Substitute decision makers will not be allowed to consent to study on a potential patient's behalf.
  • Male or female between the age of 21 to 65, inclusive.
  • Meets DSM-5 criteria for Bipolar I or II Disorder, currently experiencing a Major Depressive Episode without psychotic features. Diagnosis confirmed by study psychiatrist at the start of the parent KET-BD randomized clinical trial (RCT).
  • Patients in the KET-BD RCT 4a. Patients in the ketamine arm of the KET-BD RCT must have experienced an antidepressant response (i.e. change in MADRS score ≥ 50% at day 14 compared to baseline or Clinical Global Impression-Improvement (CGI-I) = 2 'much improved' or 1 'very much improved') or experienced clinical remission of symptoms (i.e., MADRS score < 12 on day 14) 4b. Patients in the midazolam arm of the KET-BD RCT must present as moderately to severely depressed (MADRS >21) on days 14 and 28 of the parent RCT and must be responders or remitters following four flexibly dosed infusions over 2 weeks.
  • Current depressive episode has inadequate response to two or more adequate first-line treatment trials for bipolar depression, as per the 2018 CANMAT Bipolar Disorder Guidelines. First line treatment trials include the use of lithium, valproate, carbamazepine, lamotrigine and/or any antipsychotic medication. Adequate medications confirmed at the start of the parent KET-BD RCT.
  • Patient must be receiving guideline-concordant pharmacotherapy without changes in the last month, including a therapeutic dose of a mood stabilizer.

Who cannot join

  • Currently exhibiting symptoms of mania, hypomania, or mixed state bipolar, as determined by the Young Mania Rating Scale (YMRS) score greater than 12.
  • Current symptoms of psychosis or a substance use disorder within the past 3 months. History of psychotic features during a mood episode will not be excluded.
  • History of neurological disorders (including, but not limited to, uncontrolled seizure disorder, history of stroke within past 12 months, major head injuries, aneurysmal vascular disease [including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels], arteriovenous malformation, or intracerebral hemorrhage)
  • Lifetime history of a primary psychotic disorder (including, but not limited to, schizophrenia or schizoaffective disorder)
  • Lifetime history of ketamine use disorder
  • Presence of active suicidality, requiring involuntary inpatient treatment or recent suicide attempts within the past 3 months.
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  • Presence of a contraindication to ketamine, including a drug allergy, uncontrolled hypertension (baseline systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg), low or labile blood pressure, myocardial infarction within past 12 months, cardiac arrhythmia, moderate to severe hepatic impairment (i.e., Child-Pugh score of B or C), moderate or severe renal impairment (glomerular filtration rate (GFR) < 45 milliliters/min), heart failure, or coronary artery disease
  • Pregnant or breastfeeding women or women who intend to get pregnant. Patients who are sexually active must agree to use a highly effective contraceptive method (as outlined in section 5.9).
  • Use of prohibited concomitant medications, including other forms of ketamine or esketamine, benzodiazepines, monoamine oxidase inhibitors, stimulants, medical or recreational cannabis of any form.
  • Patients in the ketamine-arm of the parent RCT, that did not reasonably tolerate 4 infusions of flexibly-dosed ketamine, as determined by the investigator and/or patient

Trial locations and contacts

3 sites in 1 country.

Canada3 sites

  • Toronto General Hospital

    Toronto, Ontario, M5G 2C4

  • Toronto Western Hospital

    Toronto, Ontario, M5T 2S8

  • Ontario Shores Centre for Mental Health Sciences

    Whitby, Ontario, L1N 5S9

Other trials in Canada

About this study

Official title: Maintenance Ketamine Infusions for Treatment-Resistant Bipolar Depression: An Open-Label Extension Trial

Growing evidence has supported rapid and robust antidepressant effects with subanesthetic doses of intravenous (IV) ketamine for treatment resistant depression (TRD). However, no completed or ongoing RCTs have evaluated the effects of repeated doses of IV ketamine for a homogenous sample of patients with treatment-resistant bipolar disorder depression (TRBD). The primary research goal is to determine the acute antidepressant efficacy, safety and tolerability of repeated sub-anesthetic maintenance doses of IV ketamine in, over a period of twelve weeks. Open-label ketamine infusions will be provided on a flexible schedule (every 2-4 weeks) with flexible dosing (0.5-1.0mg/kg over 40 minutes) titrated to optimize benefits, while minimizing the dosage and frequency over a 12-week extension period. All patients participating in this open-label study will have completed an acute course of infusions in a parent two-site, phase II, double-blinded midazolam-controlled RCT trial. In addition to this acute course of four infusions, a maximum of six infusions will be provided over the 12-week period. Secondary aims include evaluating effects of IV ketamine on suicidal ideations, quality of life, function and duration of effects. Herein, a two-site (University Health Network and Ontario Shores Centre for Mental Health Sciences), single-arm, open label, 12-week extension trial evaluating the effects of flexibly-dosed adjunctive ketamine infusions for TRBD to maintain antidepressant effects in participants who achieved an antidepressant response (MADRS decrease by >50%) or remission (MADRS < 12) following an acute course of four ketamine infusions is proposed. The primary outcome will be Montgomery-Åsberg Depression Rating Scale (MADRS) scores, determining by a linear mixed model from baseline to week 12. Secondary outcomes include evaluating response and remission rates, safety, tolerability (including treatment-emergent mania), and effects on suicidality, anxiety, quality of life, function and the duration of effects.

Being tested
Ketamine Hydrochloride
Medical subject headings
Bipolar Disorder

What participants receive

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

  • Ketamine HydrochlorideDrug

    Patients will receive ketamine hydrochloride over 12 weeks, flexible dosed between 0.5 mg/kg to 1.0 mg/kg

Study groups in NCT05339074
Study groupRoleWhat they receive
KetamineExperimentalOpen-label ketamine infusions will be provided on a flexible schedule (every 2-4 weeks) with flexible dosing (0.5-1.0mg/kg over 40 minutes) titrated to optimize benefits, while minimizing the dosage and frequency over a 12-week extension period
Receives: Drug: Ketamine Hydrochloride

What is being measured

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

  1. Change in depression severity using the Montgomery-Asberg Depression Rating Scale (MADRS)

    The MADRS is a clinician-rated scale measuring depression severity. It consists of 10 items, each scored from 0 (normal) to 6 (severe), for a total possible score of 60. A higher score is indicative of greater depressive severity. Response rates are defined as > 50% decrease and Remission <12 actual score.

    Measured: 12 weeks

Secondary outcomes (5)

  1. Recruitment and Retention Rates

    The feasibility of ketamine as a treatment in bipolar disorder will be measured by recruitment and retention rates.

    Measured: 12 weeks

  2. Treatment-Emergent Adverse Events

    Treatment-emergent adverse events will be assessed using patient-reported adverse events.

    Measured: 12 weeks

  3. Suicidality

    Suicidality will be assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS) which is a clinical assessment used to assess suicidal ideation and suicidal behaviour. It measures the incidence of suicidality via "yes" or "no" questions as well as the severity of suicidal ideation if present on a scale of 1 to 5 with 5 being the most severe.

    Measured: 12 weeks

  4. Treatment-Emergent Mania

    Treatment-emergent mania will be assessed using the Young Mania Rating Scale (YMRS) which is a clinical assessment used to evaluate manic symptoms and their severity. It consists of 11 items with a maximum possible score of 60, with higher scores indicating more severe manic symptoms.

    Measured: 12 weeks

  5. Quality of Life (QOL)

    Quality of life will be assessed using the Quality of Life-BD (QOL.BD) scale, which contains 56 questions over 12 domains. It uses a 5-component scale that evaluates mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. This scale is numbered from 56 to 280, 280 indicating a high quality of life, while 56 denotes a low quality of life.

    Measured: 12 weeks

Timeline

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

  1. First posted21 Apr 2022
  2. Study start11 Aug 2022
  3. Primary completion28 Jan 2026
  4. Study completion28 Jan 2026

Resources

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
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05339074
Sponsor's protocol ID
21-5963
Acronym
KET-BD-Sustain
Status last verified
Mar 2026
First submitted
13 Apr 2022
Last updated
5 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ketamine Hydrochloride in people with Bipolar Disorder and Bipolar Depression, run by Joshua Rosenblat at 3 sites in Canada.

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 6 inclusion and 10 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 5 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Canada. 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?

Change in depression severity using the Montgomery-Asberg Depression Rating Scale (MADRS) (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05339074.

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 5 Mar 2026.

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