Clinical TrialParallelSuicidalityKetaminePlaceboNot yet recruiting

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

This Phase II randomised, quadruple-masked trial (n=120) will study adults aged 18 to 70 years with borderline personality disorder, treatment-resistant major depressive disorder or bipolar disorder, and suicidal ideation, evaluating whether intravenous ketamine plus dialectical behavioural therapy (DBT) reduces suicidal ideation more rapidly and robustly than midazolam plus DBT. The main purpose is to assess change in suicidal ideation severity from baseline to Day 35 using the Modified Scale for Suicidal Ideation (MSSI). All participants will receive DBT for 6 months, starting before the infusions, with weekly individual sessions and the addition of weekly group sessions from Week 5. The experimental arm will receive six intravenous ketamine infusions over 1 month: the first two at 0.5 mg/kg over 40 minutes, infusions 3 and 4 flexibly dosed at 0.5 mg/kg to 0.75 mg/kg, and infusions 5 and 6 flexibly dosed at 0.5 mg/kg to 0.85 mg/kg. The comparator arm will receive six intravenous midazolam infusions over the same period: the first two at 0.02 mg/kg over 40 minutes, infusions 3 and 4 at 0.02 mg/kg to 0.03 mg/kg, and infusions 5 and 6 at 0.2 mg/kg to 0.035 mg/kg. Participants will also complete hospital visits, remote follow-up by call or videocall, and a range of mood, cognitive and behavioural assessments.

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Target Enrollment
120 participants
Study Type
Phase II interventional
Design
Randomized, quadruple Blind

Detailed Description

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

Study Protocol

Preparation

sessions

Dosing

sessions

Integration

sessions

Therapeutic Protocol

other

Study Arms & Interventions

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.

Interventions

  • Ketamine0.5 - 0.85 mg/kg
    via IV• six infusions over a month• 6 doses total

Midazolam and Dialectical Behavioural Therapy

inactive

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.

Interventions

  • Placebo0.02 - 0.035 mg/kg
    via IV• six infusions over a month• 6 doses total

    Unmatched intervention: Midazolam Hydrochloride

Participants

Ages
18 – 70
Sexes
Male & Female

Inclusion Criteria

  • 1. Adults between the age of 18 to 70, inclusive;
  • 2. Meets criteria for BPD, as determined by clinical assessment by a psychiatrist or psychologist and confirmed by the International Personality Disorder Examination (IPDE);
  • 3. 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);
  • 4. 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);
  • 5. No changes in pharmacotherapy for MDD/BD in the last month or changes in psychotherapy in the past month;
  • 6. Baseline SI as shown by two consecutive MSSI scores \> 10 two weeks apart.

Exclusion Criteria

  • 1. Past or current history of a psychotic disorder as determined by clinical assessment and MINI;
  • 2. Current or recent (within the past 3 months) manic or hypomanic episode as determined by clinical assessment via YMRS (score \> 12) and the MINI;
  • 3. Meeting criteria for Moderate to Severe Alcohol or substance use disorders currently or within the past 3 months;
  • 4. Lifetime history of ketamine use disorder or illicit ketamine use.
  • 5. Acute suicide risk requiring involuntary inpatient treatment under the Mental Health Act (MHA).
  • 6. 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);
  • 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);
  • 8. 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;
  • 9. 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;
  • 10. 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).

Study Details

  • Status
    Not yet recruiting
  • Phase
    Phase II
  • Type
    interventional
  • Design
    Randomizedquadruple Blind
  • Target Enrollment120 participants
  • Timeline
    Start: 2026-06-01
    End: 2029-08-01
  • Compounds
    KetaminePlacebo
  • Topic
    Suicidality

Locations

Canada