Ketamine With Dialectical Behavioural Therapy (DBT) for Suicidality in Individuals With Treatment-Resistant Depression and Borderline Personality Disorder (KET-DBT)

NCT07569198 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 25-5431
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to learn if intravenous (IV) ketamine with Dialectical Behavioural Therapy (DBT) reduces suicidal ideation in individuals with suicidality who have been diagnosed with Borderline Personality Disorder and either Major Depressive Disorder or Bipolar Disorder. The main question it aims to answer is: Does IV ketamine and DBT produce more rapid and robust improvements in suicidal ideation (SI) severity between baseline and Day 35 compared to IV midazolam and DBT, as measured by changes in the Modified Scale for Suicidal Ideation (MSSI) scores ? Researchers will compare six IV ketamine infusions and DBT to an active placebo (a look-alike substance that mimics some of ketamine's effects and not others) and DBT to see if IV ketamine with DBT is more effective at reducing SI severity. Participants will:

• Complete six infusions of either IV ketamine or IV midazolam
• Take part in 6 months of DBT (includes both weekly one-on-one sessions, and group sessions, starting week 5 of the trial)
• Visit the hospital for scheduled in-person visits
• Join a call or videocall for scheduled remote visits
• Complete a variety of different mood, cognitive and behavioral assessments

Conditions

Borderline Personality Disorder (BPD); Treatment-Resistant Major Depressive Disorder; Treatment-resistant Bipolar Depression; Major Depressive Disorder (MDD); Bipolar Disorder (BD); Bipolar Disorder I or II; Suicidal Ideation

Keywords

Dialectical Behavioural Therapy (DBT); ketamine; Borderline Personality Disorder; Treatment-Resistant Depression; Bipolar Disorder (BD); Major Depressive Disorder (MDD); Suicidality

Outcome Measures

Primary Outcomes (1)

• Change in suicidal ideation severity using the Modified Scale for Suicidal Ideation (MSSI)

  The MSSI is a clinician administered scale used to assess presence or absence of suicidal ideation as well as intensity of suicidal ideation in the previous 48 hours. It consists of 18 items, with each item scored from 0 to 3. Total scores are summed and severity can be categorized as low (0-3), mild (9-20), or severe (\>21).

  From Baseline to Day 35 (Primary Endpoint)

Secondary Outcomes (11)

• Changes in suicidal ideation severity over a longer period of time using the Modified Scale for Suicidal Ideation (MSSI)

  From Baseline to Month 6 and Month 9

• Changes in suicidal behavior (SB) and self-harm (SH) using the Suicide Attempt Self-Injury Interview (SASII)

  From Baseline to Months 3, 6, and 9

• Changes in suicidal behavior (SB) and self-harm (SH) using the Lifetime Suicide Attempt Self-Injury Interview (L-SASII)

  From Baseline to Months 3, 6, and 9

• Changes in depression severity using the Montgomery Asberg Depression Rating Scale (MADRS)

  From Baseline to Day 35 (Primary Endpoint), Month 6 and Month 9

• Changes in personality psychopathology evaluated using the Borderline Symptom List-23 (BSL-23)

  From Baseline to Day 35 (Primary Endpoint), Month 6 and Month 9

Study Arms (2)

Ketamine and Dialectical Behavioural Therapy

EXPERIMENTAL

All participants in the trial will receive DBT. DBT will begin prior to ketamine infusions and will continue for 6 months of the trial. There will be individual DBT and also group DBT that will begin in Week 5 of the trial. Participants in this arm will receive six infusions of ketamine over a month. The first two infusions will be dosed at 0.5mg/kg over a period of 40 minutes. For infusions 3 and 4, patients will be flexibly dosed between 0.5 mg/kg to 0.75 mg/kg, depending on clinical response to first two infusions. For infusions 5 and 6, participants will be flexibly dosed between 0.5 mg/kg to 0.85 mg/kg.

Drug: Ketamine Hydrochloride; Behavioral: Dialectical Behavioral Therapy (DBT)

Midazolam and Dialectical Behavioural Therapy

PLACEBO COMPARATOR

All participants in the trial will receive DBT. DBT will begin prior to midazolam infusions and will continue for 6 months of the trial. There will be individual DBT and also group DBT that will begin in Week 5 of the trial. Participants in this arm will receive six infusions of midazolam over a month. The first two infusions will be dosed at 0.02 mg/kg over a period of 40 minutes. For infusions 3 and 4, patients will be flexibly dosed between 0.02 mg/kg to 0.03 mg/kg, depending on clinical response to first two infusions. For infusions 5 and 6, participants will be flexibly dosed between 0.2 mg/kg to 0.035 mg/kg.

Drug: Midazolam Hydrochloride; Behavioral: Dialectical Behavioral Therapy (DBT)

Interventions

Midazolam Hydrochloride DRUG

Participants in this arm will receive six midazolam hydrochloride infusions over a month, with doses ranging between 0.02 mg/kg to 0.035 mg/kg

Midazolam and Dialectical Behavioural Therapy

Ketamine Hydrochloride DRUG

Participants in this arm will receive six ketamine hydrochloride infusions over a month, with doses ranging between 0.5 mg/kg to 0.85 mg/kg

Ketamine and Dialectical Behavioural Therapy

Dialectical Behavioral Therapy (DBT) BEHAVIORAL

All participants in this trial will receive DBT over six months. Eligible participants will begin with weekly individual sessions, followed by the addition of weekly group sessions beginning in week 5 of the trial.

Ketamine and Dialectical Behavioural Therapy; Midazolam and Dialectical Behavioural Therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults between the age of 18 to 70, inclusive;
• Meets criteria for BPD, as determined by clinical assessment by a psychiatrist or psychologist and confirmed by the International Personality Disorder Examination (IPDE);
• Meets DSM-5 criteria for MDD or BD (I or II), currently experiencing a MDE without psychotic features, as diagnosed by a study psychiatrist or psychologist. Diagnosis will be confirmed using the Mini- International Neuropsychiatric Interview (MINI);
• Current MDE must be moderate to severe, as determined by the MADRS score \>20 with an inadequate response to two or more guideline-concordant treatment trials as defined by the Antidepressant Treatment History Form-Short Form (ATHF- SF);
• No changes in pharmacotherapy for MDD/BD in the last month or changes in psychotherapy in the past month;
• Baseline SI as shown by two consecutive MSSI scores \> 10 two weeks apart.

You may not qualify if:

• Past or current history of a psychotic disorder as determined by clinical assessment and MINI;
• Current or recent (within the past 3 months) manic or hypomanic episode as determined by clinical assessment via YMRS (score \> 12) and the MINI;
• Meeting criteria for Moderate to Severe Alcohol or substance use disorders currently or within the past 3 months;
• Lifetime history of ketamine use disorder or illicit ketamine use.
• Acute suicide risk requiring involuntary inpatient treatment under the Mental Health Act (MHA).
• Presence of a relative or absolute contraindication to ketamine or midazolam, including a drug allergy, lifetime history of stroke, uncontrolled hypertension (Systolic BP \> 160 or Diastolic BP \> 100), low or labile blood pressure (Systolic BP \< 100 or Diastolic BP \< 60), recent (within the past 6 months) myocardial infarction, severe coronary artery disease (ascertained through participant's medical history), or moderate to severe renal (GFR scores ≤ 44) or hepatic impairment (A Child-Pugh score of ≥ 7);
• Currently pregnant or breastfeeding or planning on getting pregnant within the first two months of the trial or planning on getting someone else pregnant within the first two months of trial. Participants who are sexually active must agree to use a highly effective contraceptive method (please see exhaustive list in Section 3.6.1);
• Current use of prohibited concomitant medications, including other forms of ketamine or esketamine, high dose daily benzodiazepines (greater than 4 mg lorazepam equivalent daily) or monoamine oxidase inhibitors;
• Currently engaged (or completed within the past year) in DBT treatment. NOTE: Individuals who have received only DBT skills training in the past year will be considered eligible to participate;
• Those engaged in other forms of psychotherapy must be willing to discontinue for the duration of the 6-month DBT intervention (standard for DBT). There should be no changes in psychotherapy 30 days prior to baseline (i.e., Screening Visit 2).

Sponsors & Collaborators

• Joshua Rosenblat: lead

MeSH Terms

Conditions

Borderline Personality Disorder; Depressive Disorder, Major; Bipolar Disorder; Suicidal Ideation; Depressive Disorder, Treatment-Resistant

Interventions

Ketamine; Midazolam

Condition Hierarchy (Ancestors)

Personality Disorders; Mental Disorders; Depressive Disorder; Mood Disorders; Bipolar and Related Disorders; Suicide; Self-Injurious Behavior; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Joshua D. Rosenblat, MD, MSc

  Toronto Western Hospital, Psychiatry

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Orly Lipsitz

CONTACT

437-882-9458; ket.dbt@uhn.ca

Deep Grewal

CONTACT

actu@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Doctor

Study Record Dates

• First Submitted: April 13, 2026
• First Posted: May 6, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share