Combining Ketamine With Dialectical Behavioural Therapy (DBT) for Suicidality in Individuals With Treatment-Resistant Depression and Borderline Personality Disorder: A Phase II Randomized, Midazolam-Controlled Clinical Trial (KET-DBT)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Change in suicidal ideation severity using the Modified Scale for Suicidal Ideation (MSSI)
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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).
研究组 & 干预措施
Ketamine and Dialectical Behavioural Therapy
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.
干预措施: Dialectical Behavioral Therapy (DBT) (Behavioral)
Ketamine and Dialectical Behavioural Therapy
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.
干预措施: Ketamine Hydrochloride (Drug)
Midazolam and Dialectical Behavioural Therapy
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.
干预措施: Midazolam Hydrochloride (Drug)
Midazolam and Dialectical Behavioural Therapy
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.
干预措施: Dialectical Behavioral Therapy (DBT) (Behavioral)
结局指标
主要结局
Change in suicidal ideation severity using the Modified Scale for Suicidal Ideation (MSSI)
时间窗: From Baseline to Day 35 (Primary Endpoint)
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).
次要结局
- 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)
- Changes in personality psychopathology using Level of Personality Functioning Scale (LPFS)(From Baseline to Day 35 (Primary Endpoint), Month 6 and Month 9)
- Changes in personality psychopathology using the Symptom-Checklist-90-Revised (SCL-90-R)(From Baseline to Day 35 (Primary Endpoint), Month 6 and Month 9)
- Changes in anxiety as measured by the Generalized Anxiety Disorder-7 (GAD-7)(From Baseline to Day 35 (Primary Endpoint), Month 6 and Month 9)
- Safety and tolerability evaluated by Adverse Events(Across 9 Months)
- Safety and tolerability measured by using the Clinician Administered Dissociative Symptom Scale (CADSS)(Across 9 months)
- Safety and tolerability evaluated by the Brief Psychiatric Rating Scale - Positive Symptom Subscale (BPRS-PS)(Across 9 months)
研究者
Joshua Rosenblat
Doctor
University Health Network, Toronto