Integrated Internet-Based Cognitive Behavioural Therapy (i-CBT) and Intravenous Ketamine for Suicidality in Treatment-Resistant Depression: A Randomized, Midazolam-Controlled Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Suicidality severity using the Columbia-Suicide Severity Rating Scale (C-SSRS)
研究概览
简要总结
Approximately four thousand Canadians die by suicide every year, and suicide is the second leading cause of death in youth and young adults (15-34 years). Most people with depression experience thoughts of suicide and many will also plan and/or attempt suicide at some time in their life. There is an urgent need for new scalable treatments that can effectively reduce suicidality in people with depression.
Cognitive behavioural therapy (CBT) reduces suicidal thoughts and behaviours, and can be delivered through the internet (i-CBT) making it more accessible and scalable. However, i-CBT has not been shown to rapidly reduce suicidal thoughts and behaviours (suicidality), such as within 24 hours. IV ketamine on the other hand has been shown to rapidly reduce thoughts of suicide, but not suicidal behaviours.
Therefore, combining i-CBT with IV ketamine may be more effective reducing suicidality than i-CBT treatment with a control treatment.
The investigators propose a 13-week, multi-site, study that looks at how combining i-CBT and IV ketamine treatment will affect suicidality in individuals with depression who have recently experienced suicidal thoughts and/or behaviours, but have not responded to previous treatment. All 110 participants will receive a weekly session of i-CBT for 13 weeks, but half will be randomly assigned to also receive six IV ketamine treatments or six IV midazolam treatments (control treatment) over the first initial 30 days. The investigators will measure changes in suicidal thoughts and behaviours before drug treatment and at the primary endpoint (i.e.,day 30), and after 3 months (i.e. Day 91) of the starting treatment.
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
- 21 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 Major Depressive Disorder, currently experiencing a Major Depressive Episode (MDE) without psychotic features. Diagnosis will be confirmed using the Mini-International Neuropsychiatric Interview (MINI) conducted by a delegated physician or trained research study staff.
- •Must present with a moderate to severe depressive episode, as determined by the MADRS score greater than
- •Must be at risk for suicide, operationalized as a response of 'yes' to items 1 or 2 on the Suicidal Ideation subscale or 'yes to any item of the Suicidal Behaviour subscale on the C-SSRS.
- •Current MDE has inadequate response to two or more adequate first-line treatment trials for MDD, as per the 2016 CANMAT Depression Guidelines.
- •Access to reliable internet for the entire study period and an internet-based device (i.e., a smartphone, laptop, desktop or tablet).
- •Must have the ability to speak and read English. This is due to the i-CBT modules only being offered in English presently.
排除标准
- •Currently has symptoms of mania or hypomania or mixed state bipolar, as determined by the Young Mania Rating Scale (YMRS) score greater than
- •Current symptoms of psychosis or a substance use disorder within the past 3 months. Past history of psychotic features during a mood episode will not be excluded. Other secondary psychiatric comorbidities (e.g. anxiety disorders, trauma related disorders, etc.) will not be excluded.
- •Lifetime history of a primary psychotic disorder (including, but not limited to, schizophrenia or schizoaffective disorder).
- •Lifetime history of ketamine use disorder.
- •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).
- •Presence a relative or absolute contraindication to ketamine or midazolam, including a drug allergy, stroke history, uncontrolled hypertension, low or labile blood pressure (as defined by a baseline systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg), recent myocardial infarction within past 12 months, cardiac arrhythmia, severe coronary artery disease, heart failure or moderate to severe hepatic impairment (defined as a Child-Pugh score of B or C) or severe renal impairment (glomerular filtration rate (GFR) < 45 milliliters/min).
- •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.
- •Use of prohibited concomitant medications, which includes other forms of ketamine including racemic ketamine and esketamine, benzodiazepines, monoamine oxidase inhibitors, stimulants or medical cannabis of any form. All other medications will be permitted.
- •Currently receiving CBT or CBT-related interventions (e.g., Dialectical Behavioural Therapy).
- •Changes in medication or non-CBT psychotherapy one month prior to study enrollment.
研究组 & 干预措施
i-CBT and IV ketamine
Participants will receive internet-based cognitive therapy (i-CBT) for 13 weeks. During the first 4 weeks of i-CBT, participants will also be administered 6 infusions of ketamine intravenously. The first two infusions will be dosed at 0.5 mg/kg over a period of 40 mins. 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, patients will be flexibly-dosed between 0.5-0.85 mg/kg, depending on the clinical response to the first 4 infusions.
干预措施: Ketamine hydrochloride (Drug)
i-CBT and IV ketamine
Participants will receive internet-based cognitive therapy (i-CBT) for 13 weeks. During the first 4 weeks of i-CBT, participants will also be administered 6 infusions of ketamine intravenously. The first two infusions will be dosed at 0.5 mg/kg over a period of 40 mins. 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, patients will be flexibly-dosed between 0.5-0.85 mg/kg, depending on the clinical response to the first 4 infusions.
干预措施: i-CBT (Internet-based Cognitive Behavioural Therapy) (Behavioral)
i-CBT and IV midazolam
Participants will receive internet-based cognitive therapy (i-CBT) for 13 weeks. During the first 4 weeks of i-CBT, participants will also be administered 6 infusions of midazolam intravenously. The first two infusions will be dosed at 0.02 mg/kg over a period of 40 mins. 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, patients will be flexibly-dosed between 0.02 mg/kg to 0.035 mg/kg, depending on the clinical response to the first 4 infusions.
干预措施: i-CBT (Internet-based Cognitive Behavioural Therapy) (Behavioral)
i-CBT and IV midazolam
Participants will receive internet-based cognitive therapy (i-CBT) for 13 weeks. During the first 4 weeks of i-CBT, participants will also be administered 6 infusions of midazolam intravenously. The first two infusions will be dosed at 0.02 mg/kg over a period of 40 mins. 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, patients will be flexibly-dosed between 0.02 mg/kg to 0.035 mg/kg, depending on the clinical response to the first 4 infusions.
干预措施: Midazolam Hydrochloride (Drug)
结局指标
主要结局
Suicidality severity using the Columbia-Suicide Severity Rating Scale (C-SSRS)
时间窗: 30 Days, up to 91 Days.
The CSSRS evaluates suicidal ideation and behaviour. The CSSRS evaluates suicidal ideation and behaviour. The suicidal ideation score ranges from 0 (no ideation) to 5 (active suicidal ideation with specific plan and intent). Suicidal ideation intensity score ranges from 0 (no ideation) to 25 (most severe). The presence of suicidal behaviour is rated as a binary response; the lethality of actual attempts are rated on a scale of 0 (no or very minor physical damage) to 5 (death) and the potential lethality of actual attempts are rated on a scale of 0 (behaviour not likely to result in injury) to 2 (behaviour likely to result in death despite available medical care).
次要结局
- Objective Depressive Symptom Severity using the Montgomery-Asberg Depression Rating Scale (MADRS)(Day 30, Day 91)
- Dissociative Symptom Severity using the Clinician-Administered Dissociative States Scale (CADSS), 23-item(30 minutes Post-Infusion)
- Treatment-Emergent Psychiatric Symptoms using the Brief Psychiatric Rating Scale (BPRS)(30 minutes Post infusion, Day 30, Day 91)
- Treatment-Emergent Manic Symptoms using the Young Mania Rating Scale (YMRS)(30 minutes Post infusion, Day 30, Day 91)
- Subjective Cognitive Impairment using the Perceived Deficits Questionnaire - Depression - 5-Item (PDQ-5-D)(Day 30, Day 91)
- Cognitive Processing Speed using the Trail Making Test A (TMT-A)(Day 30, Day 91)
- Anxiety using the Generalized Anxiety Disorder-7 (GAD-7)(Day 30, Day 91)
- Reaction Time using the Choice Reaction Time Identification Task (CRT)(Day 30, Day 91)
- Psychomotor signs of depression using the Core Assessment of Psychomotor Change (CORE)(Day 30, Day 91)
- Verbal Memory using the California Verbal Learning Test Second Edition (CVLT-II)(Day 30, Day 91)
- Mystical Type Experiences using the Mystical Experiences Questionnaire (MEQ)(30 minutes Post Infusion, Day 30, Day 91)
- Executing Functioning using the Trail Making Test B (TMT-B)(Day 30, Day 91)
- Cognitive Function using the Digit Symbol Substitution Test (DSST)(Day 30, Day 91)
- Subjective Depressive Symptom Severity using the McIntyre and Rosenblat Rapid Response Scale (MARRRS)(Day 30, Day 91)
- Subjective Perception of pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, well-being, and shortness of breath using the Edmonton Symptom Assessment System Revised (ESAS-r)(Day 30, Day 91)
- Automatic negative self-schema using the Depression Implicit Association Test (Depression IAT)(Day 30, Day 91)
- i-CBT engagement using time spent on each i-CBT module(Weekly up to Day 91.)
- Subjective Depressive Symptom Severity using Quick Inventory for Depressive Symptomatology, Self-Report, 16-item (QIDS-SR-16)(Day 30, Day 91)
- Symptom Severity and Treatment response using the Clinical Global Impressions Scale (CGI)(Day 30, Day 91)
- Subjective Wellbeing using the World Health Organization-5 Well-Being Index (WHO-5)(Day 30, Day 91)
- Impairments in Work and Activities using the World Productivity and Impairment Questionnaire (WPAI)(Day 30, Day 91)
- Hedonic/Pleasure Capacity using the Snaith-Hamilton Pleasure Scale (SHAPS)(Day 30, Day 91)
- i-CBT engagement(Weekly up to Day 91.)
- Loneliness using the UCLA Loneliness Scale (UCLA)(Day 30, Day 91)
- Verbal Fluency using the FAS test(Day 30, Day 91)
- Borderline Personality Disorder Symptoms using the Borderline Symptom List (BSL-23)(Day 30, Day 91)
- i-CBT engagement using amount of time logged into the i-CBT platform.(Weekly up to Day 91.)
- Sleep Quality using the The Pittsburgh Sleep Quality Index (PSQI)(Day 30, Day 91)
- Depression Rumination using the The 10-item ruminative response scale (RRS-10)(Day 30, Day 91)
- Symptoms of PTSD using the PTSD Checklist for DSM-5 (PCL-5)(Day 30, Day 91)
- i-CBT engagement using number of logins per day into i-CBT platform(Weekly up to Day 91.)
- Addiction Potential Using the Drug Liking and Craving Questionnaire (DLCQ)(30 minutes Post Infusion, at Day 30, weekly after Day 30 up to Day 91.)