Clinical trial NCT03395314: Ketamine in Borderline Personality Disorder
Official title: A Randomized Active Placebo Controlled Trial of Ketamine in Borderline Personality Disorder
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Borderline Personality Disorder
Keywords: Borderline Personality Disorder
Ketamine
Suicide
Social Cognition
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Nathan Kline Institute for Psychiatric Research
name: American Foundation for Suicide Prevention
First posted: 2018-01-10
Enrollment: 22
Sex: ALL
Minimum age (years): 21
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Baseline measures of demographics, life experiences, and symptoms may also be used to predict outcomes or as co-variates in our analyses.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS)
timeFrame: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.
measure: Change in Suicidality as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.
measure: Change in Suicidality as Measured by Item-12 on the Quick Inventory of Depressive Symptomatology (QIDS SR-16)
timeFrame: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.
measure: Change in Suicidality as Measured by Item 9 on Beck Depression Inventory
timeFrame: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.
Secondary outcomes:
measure: Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
timeFrame: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.
measure: Change in Beck Depression Inventory Score
timeFrame: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.
measure: Change in Beck Anxiety Inventory Score
timeFrame: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.
measure: Change in Zanarini Rating Scale for Borderline Personality Disorder
timeFrame: Timepoints will be baseline and at 1, 3, 7, 14, & 28 days after infusion.
measure: Change in Preferred Distance in Stop-distance Paradigm (SDP)
timeFrame: Timepoints will be at baseline and 3, 7, 14, 28 days after infusion
measure: Change in Behavior in the Economic Trust Game - Cooperation
timeFrame: Timepoints will be at baseline and 3, 7, 14, 28 days after infusion
measure: Change in Social Adjustment Scale Self Report (SAS-SR) Short Version Score
timeFrame: Timepoints will be at baseline and 3, 7, 14, 28 days after infusion
measure: Change in Brief Pain Inventory Score - Intensity
timeFrame: Timepoints will be at baseline, and post-infusion 1hr, and days 1, 3, 7, 14, & 28.
measure: Change in Brief Pain Inventory Score - Interference
timeFrame: Timepoints will be at baseline, and post-infusion 1hr, and days 1, 3, 7, 14, & 28.
measure: Change in Clinician-Administered Dissociative States Scale (CADSS) Score
timeFrame: Timepoints: pre- infusion, during infusion +20, +40 minutes, and post-infusion 40 minutes.
measure: Change in Adverse Events
timeFrame: Timepoints: Continuous monitoring throughout infusion; post-infusion days 1, 3, 7, 14, 28.
measure: Change in 'Reading the Mind in the Eyes' Test (RMET) Score
timeFrame: Timepoints: at baseline and 3, 7, 14, 28 days after infusion.
measure: Change in Brief Psychiatric Rating Scale (BPRS) Total Scores
timeFrame: Timepoints: pre-infusion, during infusion +20, +40 minutes, post-infusion +40 minutes
measure: Change in Beck Suicide Scale Total Score
timeFrame: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.
Other outcomes:
measure: Change in Bias Scores on the Implicit Association Tests (IAT) of Death, Escape and Self Harm Imagery.
timeFrame: Timepoints: at baseline and 1, 3, 7, 28 days after infusion.
measure: Change in Resting State Electroencephalography (EEG)
timeFrame: Timepoints: at baseline and 1 and/or 7 days after infusion.
measure: Change in Electroencephalography (EEG) Signal During Behavioral Neuroplasticity Task
timeFrame: Timepoints: at baseline and 1 and/or 7 days after infusion.
Locations:
city: New Haven
country: United States
facility: Connecticut Mental Health Center
state: Connecticut
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
Study officials:
affiliation: Yale University
name: Sarah Fineberg, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References: