A Randomized Active Placebo Controlled Trial of Ketamine in Borderline Personality Disorder
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 22
- 试验地点
- 2
- 主要终点
- Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS)
研究概览
简要总结
The purpose of this study is to test the potential of the rapid-acting anti-depressant ketamine to decrease suicidality in Borderline Personality Disorder (BPD).
The rate of completed suicide in BPD is similar to that of depression or schizophrenia. There is currently no specific medication treatment for BPD.
Ketamine is an FDA-approved anesthetic agent that has been shown to rapidly decrease suicidality and improve mood in people with Major Depressive Disorder (MDD). Though symptoms overlap, effective treatments for MDD and BPD differ. This clinical trial tests if ketamine also decreases suicidality and improves mood in BPD.
This trial will also measure several other outcomes after ketamine versus placebo in BPD: adverse events, BPD symptoms, pain, social cognition, and neuroplasticity.
详细描述
This clinical trial primarily tests the impact of ketamine on suicidal thoughts in Borderline Personality Disorder (BPD). It also tests the impact of ketamine on symptom intensity (for mood, BPD, and pain symptoms), social cognition, and neuroplasticity in people with BPD.
Suicidal ideation and action are too common in BPD, occurring at rates similar to those in people with depression or schizophrenia. Intensive psychotherapy helps, but many people with BPD do not have access to that treatment, and not everyone responds to psychotherapy if they do get access. No medication is FDA-approved for BPD, and no medication has been shown to decrease suicidality in BPD.
Ketamine is a promising medication for this problem. It is an FDA-approved anesthetic medication with N-methyl D-aspartate activity. Sub-anesthetic doses of ketamine decrease suicidality and improve mood in people with Major Depressive Disorder (MDD). This effect is rapid, with symptom improvement within hours that endures approximately two weeks. People with BPD can have symptoms that overlap with those of MDD, however, the effective treatments for BPD and MDD differ. This clinical trial will test if ketamine, which is effective in MDD, is also effective in BPD.
The investigators will use semi-structured interviews and self-report questionnaires to measure suicidal ideation and clinical symptoms (adverse events, mood symptoms, BPD symptoms, and pain). Social cognition will be also be measured using both interviews/questionnaires and cognitive psychology tasks.
One proposed mechanism of ketamine's effect in MDD is increased neuroplasticity - opening a window during which new learning can occur. This mechanism has been demonstrated in rodent models of depression. In BPD, negatively-biased social interpretations impede meaningful recovery and increase suicide risk over time. A post-ketamine neuro-plastic window may provide an opportunity for revisions of rigid social attributions. The investigators will test for changes in neuroplasticity using a cognitive psychology task and electro-encephalography.
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 21-60
- •Clinical diagnosis of Borderline Personality Disorder
- •Has suicidal ideation.
- •Fluent in English
- •Has a current mental health treater, and agrees for study to communicate with treater
排除标准
- •Current suicidal intent
- •Med changes in last 4 weeks
- •Any ketamine in any context in the last one year.
- •Current prescription for topiramate, lamotrigine, or lithium.
- •Psychotic disorder in self or first-degree relative
- •Current substance dependence including alcohol dependence
- •Any history of NMDA (N-methyl-D-aspartate )-antagonist abuse
- •Any history of opiate abuse
- •History of major medical illness especially neurologic or cardiovascular condition, or any other medical contra-indication to ketamine administration at the discretion of the study MD.
- •Positive urine test for drugs of abuse screening on day of ketamine administration
- •Positive pregnancy test on day of ketamine administration
- •At the discretion of study staff
研究组 & 干预措施
midazolam
Midazolam IV; 0.04mg/kg over 40 minutes
干预措施: Midazolam (Drug)
low dose ketamine
ketamine IV; 0.5 mg/kg over 40 minutes
干预措施: Ketamine (Drug)
结局指标
主要结局
Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS)
时间窗: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.
The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. Scores are averaged across items and can range from 0 to 6 (with 0 indicating enjoying life, and 6 indicating explicit plans for suicide). Outcome description updated when results were entered.
Change in Suicidality as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS)
时间窗: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.
Suicide Rating Scale from 1-5; higher numbers indicate increased suicidal thinking.
Change in Suicidality as Measured by Item-12 on the Quick Inventory of Depressive Symptomatology (QIDS SR-16)
时间窗: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.
The Quick Inventory of Depressive Symptomatology (QIDS SR-16) is a a self-report measure of depression. Each item is scored from 0-3. Higher scores denote more severe load of depressive symptoms. Item 12 measures thoughts of death or suicide from 0 (no thoughts) to 3 (specific suicide plan or action.). Presented is the mean score across items with a range of 0 to 3 where the higher score indicates greater depressive symptoms. Outcome description was updated at the time of results entry.
Change in Suicidality as Measured by Item 9 on Beck Depression Inventory
时间窗: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.
When the test is scored, a value of 0 to 3 is assigned for each answer and then the total score is used to quantify the participant's degree of depression from 0 = no depression to 63 = maximally severe depression. Item 9 measures degree of suicidal thoughts or wishes from 0 = no thoughts to 3 = suicidal intent.
次要结局
- Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score(Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.)
- Change in Beck Depression Inventory Score(Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.)
- Change in Zanarini Rating Scale for Borderline Personality Disorder(Timepoints will be baseline and at 1, 3, 7, 14, & 28 days after infusion.)
- Change in Beck Anxiety Inventory Score(Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.)
- Change in Preferred Distance in Stop-distance Paradigm (SDP)(Timepoints will be at baseline and 3, 7, 14, 28 days after infusion)
- Change in Social Adjustment Scale Self Report (SAS-SR) Short Version Score(Timepoints will be at baseline and 3, 7, 14, 28 days after infusion)
- Change in Brief Pain Inventory Score - Interference(Timepoints will be at baseline, and post-infusion 1hr, and days 1, 3, 7, 14, & 28.)
- Change in Behavior in the Economic Trust Game - Cooperation(Timepoints will be at baseline and 3, 7, 14, 28 days after infusion)
- Change in Brief Pain Inventory Score - Intensity(Timepoints will be at baseline, and post-infusion 1hr, and days 1, 3, 7, 14, & 28.)
- Change in Clinician-Administered Dissociative States Scale (CADSS) Score(Timepoints: pre- infusion, during infusion +20, +40 minutes, and post-infusion 40 minutes.)
- Change in Adverse Events(Timepoints: Continuous monitoring throughout infusion; post-infusion days 1, 3, 7, 14, 28.)
- Change in 'Reading the Mind in the Eyes' Test (RMET) Score(Timepoints: at baseline and 3, 7, 14, 28 days after infusion.)
- Change in Brief Psychiatric Rating Scale (BPRS) Total Scores(Timepoints: pre-infusion, during infusion +20, +40 minutes, post-infusion +40 minutes)
- Change in Beck Suicide Scale Total Score(Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.)