Ketamine in Borderline Personality Disorder
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|ClinicalTrials.gov Identifier: NCT03395314|
Recruitment Status : Recruiting
First Posted : January 10, 2018
Last Update Posted : March 12, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Borderline Personality Disorder||Drug: Ketamine Drug: Midazolam||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||66 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomized Active Placebo Controlled Trial of Ketamine in Borderline Personality Disorder|
|Actual Study Start Date :||February 15, 2018|
|Estimated Primary Completion Date :||February 15, 2020|
|Estimated Study Completion Date :||February 15, 2020|
Placebo Comparator: midazolam
Midazolam IV; 0.04mg/kg over 40 minutes
1 single dose of IV midazolam
Active Comparator: Very low dose ketamine
ketamine IV; 0.25 mg/kg over 40 minutes
1 single dose of IV ketamine
Active Comparator: low dose ketamine
ketamine IV; 0.5 mg/kg over 40 minutes
1 single dose of IV ketamine
- Change in suicidal thoughts as measured by item 10 on the Montgomery-Asberg Depression Scale (MADRS) [ Time Frame: 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. Item 10 scores can range from 0 to 6 (with 0 indicating enjoying life, and 6 indicating explicit plans for suicide.)
- Change in suicidality as measured by the Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: 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) [ Time Frame: 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.)
- Change in suicidality as measured by item 9 on Beck Depression Inventory [ Time Frame: 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.
- Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion. ]The MADRS scale measures the depression level of a participant. The total score was derived by adding the scores of the following 10 items: 1, Apparent sadness; 2, Reported sadness; 3, Inner tension; 4, Reduced sleep; 5, Reduced appetite; 6, Concentration difficulties; 7, Lassitude; 8, Inability to feel; 9, Pessimistic thoughts; 10, Suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The maximum total score is 60; 0, no depression; 60, severely depressed.
- Change in Beck Depression Inventory score [ Time Frame: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion. ]
The Beck Depression Inventory (BDI) consisted of twenty-one questions about how the subject has been feeling in the last week. Each question has a set of at least four possible answer choices, ranging in intensity.
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.
- Change in Beck Anxiety Inventory score [ Time Frame: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion. ]
The Beck Anxiety Inventory (BDI) consisted of twenty-one questions about how the subject has been feeling in the last week. Each question has a set of at least four possible answer choices, ranging in intensity.
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 anxiety from 0 = no anxiety to 63 = maximally severe anxiety.
- Change in Zanarini Rating Scale for Borderline Personality Disorder [ Time Frame: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion. ]A dimensional self-report measure of BPD symptoms that consists of 9 items scored on a 4 point likert scale. Scores range of 0 = minimally symptomatic to 28 = maximally symptomatic for symptoms of Borderline Personality Disorder
- Change in preferred distance in Stop-distance paradigm (SDP) [ Time Frame: Timepoints will be at baseline and 3, 7, 14, 28 days after infusion ]The stop-distance paradigm is a measure of preferred interpersonal distance (PID). Subjects begin the task standing face-to-face and 6 feet away from a test confederate. On each of 3 trials, the confederate slowly approaches the subject. The subjects are instructed to say "stop" to indicate their 1) preferred conversational distance, then a closer distance 2) "if you start to feel uncomfortable". After each "stop", toe to toe distance is measured using a tape measure, and mean PID for the three trials is computed separately for conversational and uncomfortable distance.
- Change in behavior in the Economic trust game [ Time Frame: Timepoints will be at baseline and 3, 7, 14, 28 days after infusion ]The trust game is a multi-round economic exchange game. There are two roles in the game: investor and trustee. Study participants will play as the trustee. Each round, the investor is given a set number of points and can send any amount to the trustee. The investment triples and the trustee decides how much to repay the investor. Outcome measures are cooperation (amount returned to the investor) and coaxing (amount returned to investor on trials when poor prior returns from trustee have led investor to decrease investment).
- Change in Social Adjustment Scale Self Report (SAS-SR) short version score [ Time Frame: Timepoints will be at baseline and 3, 7, 14, 28 days after infusion ]This questionaire measures expressive and instrumental performance over the past two weeks in six role areas: (1) work, either as a paid worker, unpaid homemaker, or student, (2) social and leisure activities, (3) relationships with extended family, (4) role as a marital partner, (5) parental role, and (6) role within the family unit, including perceptions about economic functioning. The questions within each area cover four expressive and instrumental categories: performance at expected tasks; the amount of friction with people; finer aspects of interpersonal relations; and feelings and satisfactions. Each question is rated on a five-point scale from which role area means and an overall mean can be obtained, with higher scores denoting greater impairment. Role areas not relevant to the respondent can be skipped. Overall means are based on all items completed by the respondent. Scores range from 0 = no difficulties to 125 = broad difficulties in multiple domains.
- Change in Brief Pain Inventory score [ Time Frame: Timepoints will be at baseline, and post-infusion 1hr, and days 1, 3, 7, 14, & 28. ]
Self report inventory that assesses intensity of pain and its interference with everyday life.
Intensity: pain severity as measured by a 0 to 10 visual analogue scale. 0 = no pain, 10 = worst pain imaginable.
Interference score: Interference as measured by a 0 to 10 numerical rating scale. 0 = does not interfere, 10 = completely interferes
- Change in Clinician-Administered Dissociative States Scale (CADSS) score [ Time Frame: Timepoints: pre- infusion, during infusion +20, +40 minutes, and post-infusion 40 minutes. ]This scale captures the range of possible subjective side effects of ketamine or Midazolam. This consists of 23 questions and scores for each question range from 0-4. The maximum score is 92 with higher scores indicating more dissociative symptoms.
- Change in Adverse Events [ Time Frame: Timepoints: Continuous monitoring throughout infusion; post-infusion days 1, 3, 7, 14, 28. ]log of treatment emergent adverse events, EKG, pulse oximetry, vital signs.
- Change in 'Reading the Mind in the Eyes' test (RMET) score [ Time Frame: Timepoints: at baseline and 3, 7, 14, 28 days after infusion. ]The RMET is an advanced test of theory of mind. It is widely used to assess individual differences in social cognition and emotion recognition across different groups and cultures.
- Change in self-reported social activity [ Time Frame: Timepoints: at baseline and 3, 7, 14, 28 days after infusion. ]Social network analysis scale (adapted from Clifton et al. 2007) measures specific aspects of social activity including number of people and time spent interacting with others, nature of activity and subjective experience. Analysis will be mixed qualitative and quantitative methods.
- Change in Brief Psychiatric Rating Scale (BPRS) Total Scores [ Time Frame: Timepoints: pre-infusion, during infusion +20, +40 minutes, post-infusion +40 minutes ]BPRS is an 18-item clinician rated scale with 11 general symptom items, 5 positive-symptom items, and 2 negative symptom items scored on a 7-point scale (1=not present and 7=extremely severe), with higher score indicating greater severity of symptom. Total possible score range=18 to 126.
- Change in Beck Suicide Scale total score [ Time Frame: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion. ]The Beck Suicide Scale is a 23 item self report scale with items to specifically assess the presence and intensity of thoughts and actions related to suicidality. Each item response is on a 3 point likert, so total possible score on the scale is 3 x 21 = 63.
- Change in bias scores on the Implicit Association Tests (IAT) of death, escape and self harm imagery. [ Time Frame: Timepoints: at baseline and 1, 3, 7, 28 days after infusion. ]The Implicit Association Test measures implicit automatic associations by tracking the speed at which participants associate different groups of words. The scale is delivered electronically using an open-source software. Three distinct IATs will be administered to assess participant's implicit associations with death, escape, and self harm imagery respectively.
- Resting state electroecephalography (EEG) [ Time Frame: Change from baseline to one day after infusion. ]measurement of electrical patterns in the brain while subject is at rest with eyes open looking at fixation cross
- Electroecephalography (EEG) signal during behavioral neuroplasticity task [ Time Frame: Change from baseline to one day after infusion. ]measurement of electrical patterns in the brain while subject is performing behavioral task to measure basic neuroplasticity
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03395314
|Contact: Sarah Fineberg, MD/PhDfirstname.lastname@example.org|
|Contact: Eli Neustadter, Bs/Mscemail@example.com|
|United States, Connecticut|
|Connecticut Mental Health Center||Recruiting|
|New Haven, Connecticut, United States, 06519|
|Contact: Sarah K Fineberg, MD/PhD 203-974-7265 firstname.lastname@example.org|
|Yale New Haven Hospital||Recruiting|
|New Haven, Connecticut, United States, 06519|
|Contact: Sarah K Fineberg, MD/PhD 203-974-7265 email@example.com|
|Principal Investigator:||Sarah Fineberg, MD/PhD||Yale University|