Borderline Personality Disorder
Conditions
Keywords
Borderline Personality Disorder, Ketamine, Suicide, Social Cognition
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.
Interventions
DRUGKetamine
1 single dose of IV ketamine
DRUGMidazolam
1 single dose of IV midazolam
Sponsors
Nathan Kline Institute for Psychiatric Research
American Foundation for Suicide Prevention
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Suicidality as Measured by Item-12 on the Quick Inventory of Depressive Symptomatology (QIDS SR-16) | 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 | 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 Suicidality as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS) | 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 Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Zanarini Rating Scale for Borderline Personality Disorder | Timepoints will be baseline 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. Originally, 1hr post-infusion was included as a time frame but this was not collected at this time frame. |
| Change in Preferred Distance in Stop-distance Paradigm (SDP) | 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. A computerized version of the task may also be implemented for remote visits and administered in place of the in-person task. |
| Change in Behavior in the Economic Trust Game - Cooperation | 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). Cooperation was used as part of the evaluation in this study- coaxing was not. Outcome measure description was updated at the time of results entry. |
| 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 | 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.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. An overall adjustment |
| Change in Brief Pain Inventory Score - Interference | 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 | 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 | Timepoints: Continuous monitoring throughout infusion; post-infusion days 1, 3, 7, 14, 28. | Adverse events were tracked in a log of treatment emergent adverse events, EKG, pulse oximetry, vital signs. A count of any treatment emergent adverse events is presented through Day 28. The outcome measure description as updated when results were entered. |
| Change in 'Reading the Mind in the Eyes' Test (RMET) Score | 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. This is a score from 0-36 where higher score indicates better performance. |
| Change in Brief Psychiatric Rating Scale (BPRS) Total Scores | 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 | 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 (0-2) for each of 21 items, so possible totals range from 0-42. Higher scores indicate higher suicidality. The description was updated when results were entered. |
| Change in Brief Pain Inventory Score - Intensity | 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 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. | 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 | 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 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Bias Scores on the Implicit Association Tests (IAT) of Death, Escape and Self Harm Imagery. | 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. |
| Change in Electroencephalography (EEG) Signal During Behavioral Neuroplasticity Task | Timepoints: at baseline and 1 and/or 7 days after infusion. | measurement of electrical patterns in the brain while subject is performing behavioral task to measure basic neuroplasticity |
| Change in Resting State Electroencephalography (EEG) | Timepoints: at baseline and 1 and/or 7 days after infusion. | measurement of electrical patterns in the brain while subject is at rest with eyes open looking at fixation cross |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Midazolam Midazolam IV; 0.04mg/kg over 40 minutes
Midazolam: 1 single dose of IV midazolam | 12 |
| Low Dose Ketamine ketamine IV; 0.5 mg/kg over 40 minutes
Ketamine: 1 single dose of IV ketamine | 10 |
| Total | 22 |
Baseline characteristics
| Characteristic | Low Dose Ketamine | Total | Midazolam |
|---|---|---|---|
| Age, Continuous | 32.1 years STANDARD_DEVIATION 10.4 | 33.7 years STANDARD_DEVIATION 10.8 | 35.1 years STANDARD_DEVIATION 11.4 |
| Baseline Comorbidities Anxiety Disorders | 7 Participants | 16 Participants | 9 Participants |
| Baseline Comorbidities Bipolar Disorder | 1 Participants | 3 Participants | 2 Participants |
| Baseline Comorbidities Major Depressive Disorder | 5 Participants | 10 Participants | 5 Participants |
| Baseline Comorbidities Mild Substance Use Disorder | 3 Participants | 6 Participants | 3 Participants |
| Baseline Comorbidities Post-Traumatic Stress Disorder | 3 Participants | 7 Participants | 4 Participants |
| Education (years) | 15.0 years STANDARD_DEVIATION 2.7 | 15.7 years STANDARD_DEVIATION 2.7 | 16.3 years STANDARD_DEVIATION 2.7 |
| Race/Ethnicity, Customized Arabic | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 9 Participants | 19 Participants | 10 Participants |
| Region of Enrollment United States | 10 participants | 22 participants | 12 participants |
| Sex: Female, Male Female | 8 Participants | 18 Participants | 10 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 10 |
| other Total, other adverse events | 7 / 12 | 6 / 10 |
| serious Total, serious adverse events | 0 / 12 | 0 / 10 |
Outcome results
Primary
Change in Suicidality as Measured by Item-12 on the Quick Inventory of Depressive Symptomatology (QIDS SR-16)
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.
Time frame: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.
Population: Intention to treat.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Midazolam | Change in Suicidality as Measured by Item-12 on the Quick Inventory of Depressive Symptomatology (QIDS SR-16) | Day 14 post-infusion | 0.71 score on a scale | Standard Error 0.21 |
| Midazolam | Change in Suicidality as Measured by Item-12 on the Quick Inventory of Depressive Symptomatology (QIDS SR-16) | Day 3 post-infusion | 0.33 score on a scale | Standard Error 0.21 |
| Midazolam | Change in Suicidality as Measured by Item-12 on the Quick Inventory of Depressive Symptomatology (QIDS SR-16) | Day 28 post-infusion | 0.55 score on a scale | Standard Error 0.22 |
| Midazolam | Change in Suicidality as Measured by Item-12 on the Quick Inventory of Depressive Symptomatology (QIDS SR-16) | Day 7 post-infusion | 0.34 score on a scale | Standard Error 0.21 |
| Midazolam | Change in Suicidality as Measured by Item-12 on the Quick Inventory of Depressive Symptomatology (QIDS SR-16) | baseline | 1.25 score on a scale | Standard Error 0.21 |
| Midazolam | Change in Suicidality as Measured by Item-12 on the Quick Inventory of Depressive Symptomatology (QIDS SR-16) | Day 1 post-infusion | 0.34 score on a scale | Standard Error 0.21 |
| Midazolam | Change in Suicidality as Measured by Item-12 on the Quick Inventory of Depressive Symptomatology (QIDS SR-16) | 1hr post-infusion | 0.08 score on a scale | Standard Error 0.21 |
| Low Dose Ketamine | Change in Suicidality as Measured by Item-12 on the Quick Inventory of Depressive Symptomatology (QIDS SR-16) | Day 3 post-infusion | 0.3 score on a scale | Standard Error 0.23 |
| Low Dose Ketamine | Change in Suicidality as Measured by Item-12 on the Quick Inventory of Depressive Symptomatology (QIDS SR-16) | 1hr post-infusion | 0.2 score on a scale | Standard Error 0.23 |
| Low Dose Ketamine | Change in Suicidality as Measured by Item-12 on the Quick Inventory of Depressive Symptomatology (QIDS SR-16) | Day 1 post-infusion | 0.1 score on a scale | Standard Error 0.23 |
| Low Dose Ketamine | Change in Suicidality as Measured by Item-12 on the Quick Inventory of Depressive Symptomatology (QIDS SR-16) | Day 7 post-infusion | 0.5 score on a scale | Standard Error 0.23 |
| Low Dose Ketamine | Change in Suicidality as Measured by Item-12 on the Quick Inventory of Depressive Symptomatology (QIDS SR-16) | Day 14 post-infusion | 0.7 score on a scale | Standard Error 0.23 |
| Low Dose Ketamine | Change in Suicidality as Measured by Item-12 on the Quick Inventory of Depressive Symptomatology (QIDS SR-16) | Day 28 post-infusion | 1.21 score on a scale | Standard Error 0.23 |
| Low Dose Ketamine | Change in Suicidality as Measured by Item-12 on the Quick Inventory of Depressive Symptomatology (QIDS SR-16) | baseline | 1.5 score on a scale | Standard Error 0.23 |
Primary
Change in Suicidality as Measured by Item 9 on Beck Depression Inventory
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.
Time frame: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.
Population: Intention to treat.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Midazolam | Change in Suicidality as Measured by Item 9 on Beck Depression Inventory | Day 1 post-infusion | 0.36 units on a scale | Standard Error 0.19 |
| Midazolam | Change in Suicidality as Measured by Item 9 on Beck Depression Inventory | Day 7 post-infusion | 0.41 units on a scale | Standard Error 0.19 |
| Midazolam | Change in Suicidality as Measured by Item 9 on Beck Depression Inventory | 1hr post-infusion | 0.08 units on a scale | Standard Error 0.19 |
| Midazolam | Change in Suicidality as Measured by Item 9 on Beck Depression Inventory | Day 14 post-infusion | 0.5 units on a scale | Standard Error 0.19 |
| Midazolam | Change in Suicidality as Measured by Item 9 on Beck Depression Inventory | Day 3 post-infusion | 0.24 units on a scale | Standard Error 0.19 |
| Midazolam | Change in Suicidality as Measured by Item 9 on Beck Depression Inventory | Day 28 post-infusion | 0.70 units on a scale | Standard Error 0.19 |
| Midazolam | Change in Suicidality as Measured by Item 9 on Beck Depression Inventory | baseline | 1.16 units on a scale | Standard Error 0.19 |
| Low Dose Ketamine | Change in Suicidality as Measured by Item 9 on Beck Depression Inventory | Day 28 post-infusion | 0.56 units on a scale | Standard Error 0.21 |
| Low Dose Ketamine | Change in Suicidality as Measured by Item 9 on Beck Depression Inventory | baseline | 1.2 units on a scale | Standard Error 0.21 |
| Low Dose Ketamine | Change in Suicidality as Measured by Item 9 on Beck Depression Inventory | 1hr post-infusion | 0.1 units on a scale | Standard Error 0.21 |
| Low Dose Ketamine | Change in Suicidality as Measured by Item 9 on Beck Depression Inventory | Day 1 post-infusion | 0.3 units on a scale | Standard Error 0.21 |
| Low Dose Ketamine | Change in Suicidality as Measured by Item 9 on Beck Depression Inventory | Day 3 post-infusion | 0.3 units on a scale | Standard Error 0.21 |
| Low Dose Ketamine | Change in Suicidality as Measured by Item 9 on Beck Depression Inventory | Day 7 post-infusion | 0.3 units on a scale | Standard Error 0.21 |
| Low Dose Ketamine | Change in Suicidality as Measured by Item 9 on Beck Depression Inventory | Day 14 post-infusion | 0.3 units on a scale | Standard Error 0.21 |
Primary
Change in Suicidality as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS)
Suicide Rating Scale from 1-5; higher numbers indicate increased suicidal thinking.
Time frame: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.
Population: Intention to treat.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Midazolam | Change in Suicidality as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS) | baseline | 1.58 score on a scale | Standard Error 0.31 |
| Midazolam | Change in Suicidality as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS) | Day 7 post-infusion | 0.83 score on a scale | Standard Error 0.31 |
| Midazolam | Change in Suicidality as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS) | 1hr post-infusion | 0 score on a scale | Standard Error 0.31 |
| Midazolam | Change in Suicidality as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS) | Day 14 post-infusion | 0.91 score on a scale | Standard Error 0.31 |
| Midazolam | Change in Suicidality as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS) | Day 3 post-infusion | 0.75 score on a scale | Standard Error 0.31 |
| Midazolam | Change in Suicidality as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS) | Day 28 post-infusion | 1.16 score on a scale | Standard Error 0.31 |
| Midazolam | Change in Suicidality as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS) | Day 1 post-infusion | 0 score on a scale | Standard Error 0.31 |
| Low Dose Ketamine | Change in Suicidality as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS) | Day 28 post-infusion | 1.6 score on a scale | Standard Error 0.34 |
| Low Dose Ketamine | Change in Suicidality as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS) | 1hr post-infusion | 0.0 score on a scale | Standard Error 0.34 |
| Low Dose Ketamine | Change in Suicidality as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS) | Day 1 post-infusion | 0.0 score on a scale | Standard Error 0.34 |
| Low Dose Ketamine | Change in Suicidality as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS) | Day 3 post-infusion | 0.5 score on a scale | Standard Error 0.34 |
| Low Dose Ketamine | Change in Suicidality as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS) | Day 7 post-infusion | 0.3 score on a scale | Standard Error 0.34 |
| Low Dose Ketamine | Change in Suicidality as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS) | Day 14 post-infusion | 0.8 score on a scale | Standard Error 0.34 |
| Low Dose Ketamine | Change in Suicidality as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS) | baseline | 1.9 score on a scale | Standard Error 0.34 |
Primary
Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS)
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.
Time frame: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.
Population: Intention to treat.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Midazolam | Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS) | Day 3 post-infusion | 0.89 units on a scale | Standard Error 0.38 |
| Midazolam | Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS) | Day 1 post-infusion | 0.59 units on a scale | Standard Error 0.38 |
| Midazolam | Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS) | Day 28 post-infusion | 1.29 units on a scale | Standard Error 0.4 |
| Midazolam | Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS) | baseline | 2.66 units on a scale | Standard Error 0.37 |
| Midazolam | Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS) | Day 7 post-infusion | 0.83 units on a scale | Standard Error 0.37 |
| Midazolam | Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS) | Day 14 post-infusion | 1.66 units on a scale | Standard Error 0.37 |
| Midazolam | Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS) | 1hr post-infusion | 0.0 units on a scale | Standard Error 0.37 |
| Low Dose Ketamine | Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS) | Day 28 post-infusion | 2.6 units on a scale | Standard Error 0.42 |
| Low Dose Ketamine | Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS) | 1hr post-infusion | 0.1 units on a scale | Standard Error 0.41 |
| Low Dose Ketamine | Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS) | Day 1 post-infusion | 0.5 units on a scale | Standard Error 0.41 |
| Low Dose Ketamine | Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS) | Day 3 post-infusion | 0.7 units on a scale | Standard Error 0.41 |
| Low Dose Ketamine | Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS) | Day 7 post-infusion | 0.8 units on a scale | Standard Error 0.41 |
| Low Dose Ketamine | Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS) | Day 14 post-infusion | 1.3 units on a scale | Standard Error 0.41 |
| Low Dose Ketamine | Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS) | baseline | 2.7 units on a scale | Standard Error 0.41 |
Secondary
Change in Adverse Events
Adverse events were tracked in a log of treatment emergent adverse events, EKG, pulse oximetry, vital signs. A count of any treatment emergent adverse events is presented through Day 28. The outcome measure description as updated when results were entered.
Time frame: Timepoints: Continuous monitoring throughout infusion; post-infusion days 1, 3, 7, 14, 28.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Midazolam | Change in Adverse Events | 0 Participants |
| Low Dose Ketamine | Change in Adverse Events | 0 Participants |
Secondary
Change in Beck Anxiety Inventory Score
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.
Time frame: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.
Population: Intention to treat.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Midazolam | Change in Beck Anxiety Inventory Score | Day 1 | 7.43 score on a scale | Standard Error 2.57 |
| Midazolam | Change in Beck Anxiety Inventory Score | Day 7 | 7.43 score on a scale | Standard Error 2.57 |
| Midazolam | Change in Beck Anxiety Inventory Score | 1hr post-infusion | 4.0 score on a scale | Standard Error 2.51 |
| Midazolam | Change in Beck Anxiety Inventory Score | Day 14 | 8.88 score on a scale | Standard Error 2.57 |
| Midazolam | Change in Beck Anxiety Inventory Score | Baseline | 21.75 score on a scale | Standard Error 2.51 |
| Midazolam | Change in Beck Anxiety Inventory Score | Day 28 | 6.34 score on a scale | Standard Error 2.65 |
| Midazolam | Change in Beck Anxiety Inventory Score | Day 3 | 5.71 score on a scale | Standard Error 2.71 |
| Low Dose Ketamine | Change in Beck Anxiety Inventory Score | Day 28 | 18.23 score on a scale | Standard Error 2.91 |
| Low Dose Ketamine | Change in Beck Anxiety Inventory Score | Baseline | 21.7 score on a scale | Standard Error 2.75 |
| Low Dose Ketamine | Change in Beck Anxiety Inventory Score | Day 1 | 8.3 score on a scale | Standard Error 2.75 |
| Low Dose Ketamine | Change in Beck Anxiety Inventory Score | Day 3 | 5.5 score on a scale | Standard Error 2.75 |
| Low Dose Ketamine | Change in Beck Anxiety Inventory Score | Day 7 | 8.2 score on a scale | Standard Error 2.75 |
| Low Dose Ketamine | Change in Beck Anxiety Inventory Score | Day 14 | 11.0 score on a scale | Standard Error 2.75 |
| Low Dose Ketamine | Change in Beck Anxiety Inventory Score | 1hr post-infusion | 7.3 score on a scale | Standard Error 2.75 |
Secondary
Change in Beck Depression Inventory Score
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.
Time frame: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.
Population: Intention to treat.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Midazolam | Change in Beck Depression Inventory Score | Day 3 | 10.94 score on a scale | Standard Error 4.04 |
| Midazolam | Change in Beck Depression Inventory Score | Baseline | 30.75 score on a scale | Standard Error 3.96 |
| Midazolam | Change in Beck Depression Inventory Score | Day 1 | 12.41 score on a scale | Standard Error 4.04 |
| Midazolam | Change in Beck Depression Inventory Score | Day 14 | 17.41 score on a scale | Standard Error 3.96 |
| Midazolam | Change in Beck Depression Inventory Score | Day 7 | 11.33 score on a scale | Standard Error 3.96 |
| Midazolam | Change in Beck Depression Inventory Score | Day 28 | 17.57 score on a scale | Standard Error 4.04 |
| Midazolam | Change in Beck Depression Inventory Score | 1hr post-infusion | 11.16 score on a scale | Standard Error 3.96 |
| Low Dose Ketamine | Change in Beck Depression Inventory Score | Day 28 | 18.73 score on a scale | Standard Error 4.44 |
| Low Dose Ketamine | Change in Beck Depression Inventory Score | 1hr post-infusion | 13.3 score on a scale | Standard Error 4.34 |
| Low Dose Ketamine | Change in Beck Depression Inventory Score | Day 1 | 12.2 score on a scale | Standard Error 4.34 |
| Low Dose Ketamine | Change in Beck Depression Inventory Score | Day 3 | 8.9 score on a scale | Standard Error 4.34 |
| Low Dose Ketamine | Change in Beck Depression Inventory Score | Day 7 | 12.6 score on a scale | Standard Error 4.34 |
| Low Dose Ketamine | Change in Beck Depression Inventory Score | Baseline | 34.9 score on a scale | Standard Error 4.34 |
| Low Dose Ketamine | Change in Beck Depression Inventory Score | Day 14 | 14.5 score on a scale | Standard Error 4.34 |
Secondary
Change in Beck Suicide Scale Total Score
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 (0-2) for each of 21 items, so possible totals range from 0-42. Higher scores indicate higher suicidality. The description was updated when results were entered.
Time frame: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.
Population: Intention to treat.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Midazolam | Change in Beck Suicide Scale Total Score | Day 1 | 3.13 score on a scale | Standard Error 1.79 |
| Midazolam | Change in Beck Suicide Scale Total Score | Baseline | 7.66 score on a scale | Standard Error 1.75 |
| Midazolam | Change in Beck Suicide Scale Total Score | Day 14 | 5.66 score on a scale | Standard Error 1.75 |
| Midazolam | Change in Beck Suicide Scale Total Score | 1hr post-infusion | 3.5 score on a scale | Standard Error 1.75 |
| Midazolam | Change in Beck Suicide Scale Total Score | Day 3 | 2.92 score on a scale | Standard Error 1.79 |
| Midazolam | Change in Beck Suicide Scale Total Score | Day 7 | 3.08 score on a scale | Standard Error 1.75 |
| Midazolam | Change in Beck Suicide Scale Total Score | Day 28 | 4.51 score on a scale | Standard Error 1.79 |
| Low Dose Ketamine | Change in Beck Suicide Scale Total Score | 1hr post-infusion | 4.1 score on a scale | Standard Error 1.91 |
| Low Dose Ketamine | Change in Beck Suicide Scale Total Score | Day 1 | 3.3 score on a scale | Standard Error 1.91 |
| Low Dose Ketamine | Change in Beck Suicide Scale Total Score | Day 7 | 4.6 score on a scale | Standard Error 1.91 |
| Low Dose Ketamine | Change in Beck Suicide Scale Total Score | Day 14 | 5.4 score on a scale | Standard Error 1.91 |
| Low Dose Ketamine | Change in Beck Suicide Scale Total Score | Day 28 | 7.12 score on a scale | Standard Error 1.97 |
| Low Dose Ketamine | Change in Beck Suicide Scale Total Score | Baseline | 11.5 score on a scale | Standard Error 1.91 |
| Low Dose Ketamine | Change in Beck Suicide Scale Total Score | Day 3 | 3.9 score on a scale | Standard Error 1.91 |
Secondary
Change in Behavior in the Economic Trust Game - Cooperation
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). Cooperation was used as part of the evaluation in this study- coaxing was not. Outcome measure description was updated at the time of results entry.
Time frame: Timepoints will be at baseline and 3, 7, 14, 28 days after infusion
Population: Intention to treat.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Midazolam | Change in Behavior in the Economic Trust Game - Cooperation | Baseline | 0.39 proportion of amount returned | Standard Error 0.05 |
| Midazolam | Change in Behavior in the Economic Trust Game - Cooperation | Day 7 | 0.42 proportion of amount returned | Standard Error 0.05 |
| Midazolam | Change in Behavior in the Economic Trust Game - Cooperation | Day 3 | 0.36 proportion of amount returned | Standard Error 0.05 |
| Midazolam | Change in Behavior in the Economic Trust Game - Cooperation | Day 28 | 0.31 proportion of amount returned | Standard Error 0.09 |
| Midazolam | Change in Behavior in the Economic Trust Game - Cooperation | Day 14 | 0.34 proportion of amount returned | Standard Error 0.05 |
| Low Dose Ketamine | Change in Behavior in the Economic Trust Game - Cooperation | Day 28 | 0.31 proportion of amount returned | Standard Error 0.06 |
| Low Dose Ketamine | Change in Behavior in the Economic Trust Game - Cooperation | Day 14 | 0.39 proportion of amount returned | Standard Error 0.06 |
| Low Dose Ketamine | Change in Behavior in the Economic Trust Game - Cooperation | Baseline | 0.38 proportion of amount returned | Standard Error 0.06 |
| Low Dose Ketamine | Change in Behavior in the Economic Trust Game - Cooperation | Day 3 | 0.42 proportion of amount returned | Standard Error 0.06 |
| Low Dose Ketamine | Change in Behavior in the Economic Trust Game - Cooperation | Day 7 | 0.29 proportion of amount returned | Standard Error 0.06 |
Secondary
Change in Brief Pain Inventory Score - Intensity
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
Time frame: Timepoints will be at baseline, and post-infusion 1hr, and days 1, 3, 7, 14, & 28.
Population: Intention to treat.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Midazolam | Change in Brief Pain Inventory Score - Intensity | Post-infusion 1hr | 5.75 score on a scale | Standard Error 1.64 |
| Midazolam | Change in Brief Pain Inventory Score - Intensity | Day 28 | 6.28 score on a scale | Standard Error 1.62 |
| Midazolam | Change in Brief Pain Inventory Score - Intensity | Baseline | 6.19 score on a scale | Standard Error 0.93 |
| Midazolam | Change in Brief Pain Inventory Score - Intensity | Day 1 | 6.52 score on a scale | Standard Error 1.34 |
| Midazolam | Change in Brief Pain Inventory Score - Intensity | Day 3 | 6.73 score on a scale | Standard Error 1.61 |
| Midazolam | Change in Brief Pain Inventory Score - Intensity | Day 7 | 9.04 score on a scale | Standard Error 2.22 |
| Midazolam | Change in Brief Pain Inventory Score - Intensity | Day 14 | 3.2 score on a scale | Standard Error 1.33 |
| Low Dose Ketamine | Change in Brief Pain Inventory Score - Intensity | Day 28 | 5.11 score on a scale | Standard Error 1.33 |
| Low Dose Ketamine | Change in Brief Pain Inventory Score - Intensity | Day 3 | 4.46 score on a scale | Standard Error 2.28 |
| Low Dose Ketamine | Change in Brief Pain Inventory Score - Intensity | Day 14 | 4.14 score on a scale | Standard Error 1.16 |
| Low Dose Ketamine | Change in Brief Pain Inventory Score - Intensity | Baseline | 6.32 score on a scale | Standard Error 1.03 |
| Low Dose Ketamine | Change in Brief Pain Inventory Score - Intensity | Post-infusion 1hr | 2.56 score on a scale | Standard Error 2.23 |
| Low Dose Ketamine | Change in Brief Pain Inventory Score - Intensity | Day 7 | 5.92 score on a scale | Standard Error 1.16 |
| Low Dose Ketamine | Change in Brief Pain Inventory Score - Intensity | Day 1 | 4.46 score on a scale | Standard Error 2.28 |
Secondary
Change in Brief Pain Inventory Score - Interference
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
Time frame: Timepoints will be at baseline, and post-infusion 1hr, and days 1, 3, 7, 14, & 28.
Population: Intention to treat.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Midazolam | Change in Brief Pain Inventory Score - Interference | Day 1 | 4.79 score on a scale | Standard Error 1.34 |
| Midazolam | Change in Brief Pain Inventory Score - Interference | Day 7 | 4.06 score on a scale | Standard Error 1.95 |
| Midazolam | Change in Brief Pain Inventory Score - Interference | Baseline | 3.49 score on a scale | Standard Error 1.05 |
| Midazolam | Change in Brief Pain Inventory Score - Interference | Day 14 | 2.21 score on a scale | Standard Error 1.36 |
| Midazolam | Change in Brief Pain Inventory Score - Interference | Day 3 | 3.41 score on a scale | Standard Error 1.51 |
| Midazolam | Change in Brief Pain Inventory Score - Interference | Day 28 | 4.23 score on a scale | Standard Error 1.64 |
| Midazolam | Change in Brief Pain Inventory Score - Interference | Post-infusion 1hr | 1.22 score on a scale | Standard Error 1.58 |
| Low Dose Ketamine | Change in Brief Pain Inventory Score - Interference | Day 28 | 4.52 score on a scale | Standard Error 1.36 |
| Low Dose Ketamine | Change in Brief Pain Inventory Score - Interference | Post-infusion 1hr | 0.51 score on a scale | Standard Error 1.94 |
| Low Dose Ketamine | Change in Brief Pain Inventory Score - Interference | Baseline | 2.94 score on a scale | Standard Error 1.13 |
| Low Dose Ketamine | Change in Brief Pain Inventory Score - Interference | Day 1 | 3.1 score on a scale | Standard Error 2.03 |
| Low Dose Ketamine | Change in Brief Pain Inventory Score - Interference | Day 3 | 3.1 score on a scale | Standard Error 2.03 |
| Low Dose Ketamine | Change in Brief Pain Inventory Score - Interference | Day 7 | 4.09 score on a scale | Standard Error 1.36 |
| Low Dose Ketamine | Change in Brief Pain Inventory Score - Interference | Day 14 | 3.45 score on a scale | Standard Error 1.19 |
Secondary
Change in Brief Psychiatric Rating Scale (BPRS) Total Scores
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.
Time frame: Timepoints: pre-infusion, during infusion +20, +40 minutes, post-infusion +40 minutes
Population: Intention to treat.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Midazolam | Change in Brief Psychiatric Rating Scale (BPRS) Total Scores | Baseline (pre-infusion) | 29.36 score on a scale | Standard Error 2.34 |
| Midazolam | Change in Brief Psychiatric Rating Scale (BPRS) Total Scores | 20 Minutes (during infusion) | 28.18 score on a scale | Standard Error 1.81 |
| Midazolam | Change in Brief Psychiatric Rating Scale (BPRS) Total Scores | 40 Minutes (during infusion) | 28.0 score on a scale | Standard Error 1.81 |
| Midazolam | Change in Brief Psychiatric Rating Scale (BPRS) Total Scores | 80 Minutes (post infusion) | 25.9 score on a scale | Standard Error 1.81 |
| Low Dose Ketamine | Change in Brief Psychiatric Rating Scale (BPRS) Total Scores | 80 Minutes (post infusion) | 28.2 score on a scale | Standard Error 1.9 |
| Low Dose Ketamine | Change in Brief Psychiatric Rating Scale (BPRS) Total Scores | Baseline (pre-infusion) | 33.79 score on a scale | Standard Error 2.2 |
| Low Dose Ketamine | Change in Brief Psychiatric Rating Scale (BPRS) Total Scores | 40 Minutes (during infusion) | 36.2 score on a scale | Standard Error 1.9 |
| Low Dose Ketamine | Change in Brief Psychiatric Rating Scale (BPRS) Total Scores | 20 Minutes (during infusion) | 38.7 score on a scale | Standard Error 1.9 |
Secondary
Change in Clinician-Administered Dissociative States Scale (CADSS) Score
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.
Time frame: Timepoints: pre- infusion, during infusion +20, +40 minutes, and post-infusion 40 minutes.
Population: Intention to treat.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Midazolam | Change in Clinician-Administered Dissociative States Scale (CADSS) Score | Baseline (pre-infusion) | 5.94 score on a scale | Standard Error 4.11 |
| Midazolam | Change in Clinician-Administered Dissociative States Scale (CADSS) Score | 20 minutes (during infusion) | 5.54 score on a scale | Standard Error 3.46 |
| Midazolam | Change in Clinician-Administered Dissociative States Scale (CADSS) Score | 40 minutes (during infusion) | 9.54 score on a scale | Standard Error 3.46 |
| Midazolam | Change in Clinician-Administered Dissociative States Scale (CADSS) Score | 80 minutes (post infusion) | 1.90 score on a scale | Standard Error 3.46 |
| Low Dose Ketamine | Change in Clinician-Administered Dissociative States Scale (CADSS) Score | 80 minutes (post infusion) | 3.0 score on a scale | Standard Error 3.63 |
| Low Dose Ketamine | Change in Clinician-Administered Dissociative States Scale (CADSS) Score | Baseline (pre-infusion) | 5.92 score on a scale | Standard Error 3.99 |
| Low Dose Ketamine | Change in Clinician-Administered Dissociative States Scale (CADSS) Score | 40 minutes (during infusion) | 16.8 score on a scale | Standard Error 3.63 |
| Low Dose Ketamine | Change in Clinician-Administered Dissociative States Scale (CADSS) Score | 20 minutes (during infusion) | 25.4 score on a scale | Standard Error 3.63 |
Secondary
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
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.
Time frame: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.
Population: Intention to treat.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Midazolam | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Day 1 | 9.27 score on a scale | Standard Error 2.78 |
| Midazolam | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Day 7 | 12.5 score on a scale | Standard Error 2.71 |
| Midazolam | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | 1hr post-infusion | 3.66 score on a scale | Standard Error 2.71 |
| Midazolam | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Day 14 | 19.25 score on a scale | Standard Error 2.71 |
| Midazolam | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Day 3 | 11.70 score on a scale | Standard Error 2.78 |
| Midazolam | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Day 28 | 17.39 score on a scale | Standard Error 2.85 |
| Midazolam | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Baseline | 26.75 score on a scale | Standard Error 2.71 |
| Low Dose Ketamine | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Day 28 | 22.67 score on a scale | Standard Error 3.06 |
| Low Dose Ketamine | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Baseline | 28.3 score on a scale | Standard Error 2.97 |
| Low Dose Ketamine | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | 1hr post-infusion | 6.2 score on a scale | Standard Error 2.97 |
| Low Dose Ketamine | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Day 1 | 8.2 score on a scale | Standard Error 2.97 |
| Low Dose Ketamine | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Day 3 | 12.2 score on a scale | Standard Error 2.97 |
| Low Dose Ketamine | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Day 7 | 12.3 score on a scale | Standard Error 2.97 |
| Low Dose Ketamine | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Day 14 | 12.9 score on a scale | Standard Error 2.97 |
Secondary
Change in Preferred Distance in Stop-distance Paradigm (SDP)
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. A computerized version of the task may also be implemented for remote visits and administered in place of the in-person task.
Time frame: Timepoints will be at baseline and 3, 7, 14, 28 days after infusion
Population: Intention to treat.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Midazolam | Change in Preferred Distance in Stop-distance Paradigm (SDP) | Day 7 | 14.7 distance in inches | Standard Error 2.11 |
| Midazolam | Change in Preferred Distance in Stop-distance Paradigm (SDP) | Day 14 | 19.4 distance in inches | Standard Error 1.97 |
| Midazolam | Change in Preferred Distance in Stop-distance Paradigm (SDP) | Baseline | 18.6 distance in inches | Standard Error 1.97 |
| Midazolam | Change in Preferred Distance in Stop-distance Paradigm (SDP) | Day 28 | 17.2 distance in inches | Standard Error 2.11 |
| Midazolam | Change in Preferred Distance in Stop-distance Paradigm (SDP) | Day 3 | 17.3 distance in inches | Standard Error 2.12 |
| Low Dose Ketamine | Change in Preferred Distance in Stop-distance Paradigm (SDP) | Day 28 | 19.5 distance in inches | Standard Error 2.63 |
| Low Dose Ketamine | Change in Preferred Distance in Stop-distance Paradigm (SDP) | Day 3 | 17.2 distance in inches | Standard Error 2.5 |
| Low Dose Ketamine | Change in Preferred Distance in Stop-distance Paradigm (SDP) | Day 7 | 15.5 distance in inches | Standard Error 2.5 |
| Low Dose Ketamine | Change in Preferred Distance in Stop-distance Paradigm (SDP) | Baseline | 20.6 distance in inches | Standard Error 2.5 |
| Low Dose Ketamine | Change in Preferred Distance in Stop-distance Paradigm (SDP) | Day 14 | 16.5 distance in inches | Standard Error 2.5 |
Secondary
Change in 'Reading the Mind in the Eyes' Test (RMET) Score
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. This is a score from 0-36 where higher score indicates better performance.
Time frame: Timepoints: at baseline and 3, 7, 14, 28 days after infusion.
Population: Intention to treat.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Midazolam | Change in 'Reading the Mind in the Eyes' Test (RMET) Score | Baseline | 28.2 score on a scale | Standard Error 1.11 |
| Midazolam | Change in 'Reading the Mind in the Eyes' Test (RMET) Score | Day 7 | 29.2 score on a scale | Standard Error 1.11 |
| Midazolam | Change in 'Reading the Mind in the Eyes' Test (RMET) Score | Day 28 | 29.9 score on a scale | Standard Error 1.11 |
| Midazolam | Change in 'Reading the Mind in the Eyes' Test (RMET) Score | Day 14 | 29.9 score on a scale | Standard Error 1.11 |
| Midazolam | Change in 'Reading the Mind in the Eyes' Test (RMET) Score | Day 3 | 27.6 score on a scale | Standard Error 1.13 |
| Low Dose Ketamine | Change in 'Reading the Mind in the Eyes' Test (RMET) Score | Day 28 | 25.4 score on a scale | Standard Error 1.26 |
| Low Dose Ketamine | Change in 'Reading the Mind in the Eyes' Test (RMET) Score | Baseline | 25.6 score on a scale | Standard Error 1.23 |
| Low Dose Ketamine | Change in 'Reading the Mind in the Eyes' Test (RMET) Score | Day 3 | 27.3 score on a scale | Standard Error 1.23 |
| Low Dose Ketamine | Change in 'Reading the Mind in the Eyes' Test (RMET) Score | Day 7 | 26.6 score on a scale | Standard Error 1.23 |
| Low Dose Ketamine | Change in 'Reading the Mind in the Eyes' Test (RMET) Score | Day 14 | 25.1 score on a scale | Standard Error 1.23 |
Secondary
Change in Social Adjustment Scale Self Report (SAS-SR) Short Version Score
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.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. An overall adjustment
Time frame: Timepoints will be at baseline and 3, 7, 14, 28 days after infusion
Population: Intention to treat.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Midazolam | Change in Social Adjustment Scale Self Report (SAS-SR) Short Version Score | Baseline | 2.86 score on a scale | Standard Error 0.18 |
| Midazolam | Change in Social Adjustment Scale Self Report (SAS-SR) Short Version Score | Day 14 | 2.58 score on a scale | Standard Error 0.18 |
| Midazolam | Change in Social Adjustment Scale Self Report (SAS-SR) Short Version Score | Day 7 | 2.17 score on a scale | Standard Error 0.19 |
| Midazolam | Change in Social Adjustment Scale Self Report (SAS-SR) Short Version Score | Day 28 | 2.33 score on a scale | Standard Error 0.19 |
| Midazolam | Change in Social Adjustment Scale Self Report (SAS-SR) Short Version Score | Day 3 | 2.30 score on a scale | Standard Error 0.19 |
| Low Dose Ketamine | Change in Social Adjustment Scale Self Report (SAS-SR) Short Version Score | Day 28 | 2.12 score on a scale | Standard Error 0.2 |
| Low Dose Ketamine | Change in Social Adjustment Scale Self Report (SAS-SR) Short Version Score | Baseline | 2.74 score on a scale | Standard Error 0.2 |
| Low Dose Ketamine | Change in Social Adjustment Scale Self Report (SAS-SR) Short Version Score | Day 3 | 1.95 score on a scale | Standard Error 0.2 |
| Low Dose Ketamine | Change in Social Adjustment Scale Self Report (SAS-SR) Short Version Score | Day 7 | 2.02 score on a scale | Standard Error 0.2 |
| Low Dose Ketamine | Change in Social Adjustment Scale Self Report (SAS-SR) Short Version Score | Day 14 | 2.07 score on a scale | Standard Error 0.2 |
Secondary
Change in Zanarini Rating Scale for Borderline Personality Disorder
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. Originally, 1hr post-infusion was included as a time frame but this was not collected at this time frame.
Time frame: Timepoints will be baseline and at 1, 3, 7, 14, & 28 days after infusion.
Population: Intention to treat.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Midazolam | Change in Zanarini Rating Scale for Borderline Personality Disorder | Baseline | 14.33 score on a scale | Standard Error 1.78 |
| Midazolam | Change in Zanarini Rating Scale for Borderline Personality Disorder | Day 1 | 3.52 score on a scale | Standard Error 1.81 |
| Midazolam | Change in Zanarini Rating Scale for Borderline Personality Disorder | Day 3 | 5.04 score on a scale | Standard Error 1.81 |
| Midazolam | Change in Zanarini Rating Scale for Borderline Personality Disorder | Day 7 | 5 score on a scale | Standard Error 1.78 |
| Midazolam | Change in Zanarini Rating Scale for Borderline Personality Disorder | Day 14 | 6.75 score on a scale | Standard Error 1.78 |
| Midazolam | Change in Zanarini Rating Scale for Borderline Personality Disorder | Day 28 | 7.16 score on a scale | Standard Error 1.81 |
| Low Dose Ketamine | Change in Zanarini Rating Scale for Borderline Personality Disorder | Day 14 | 7.2 score on a scale | Standard Error 1.95 |
| Low Dose Ketamine | Change in Zanarini Rating Scale for Borderline Personality Disorder | Baseline | 15.4 score on a scale | Standard Error 1.95 |
| Low Dose Ketamine | Change in Zanarini Rating Scale for Borderline Personality Disorder | Day 7 | 6.8 score on a scale | Standard Error 1.95 |
| Low Dose Ketamine | Change in Zanarini Rating Scale for Borderline Personality Disorder | Day 1 | 5.2 score on a scale | Standard Error 1.95 |
| Low Dose Ketamine | Change in Zanarini Rating Scale for Borderline Personality Disorder | Day 28 | 11.42 score on a scale | Standard Error 1.99 |
| Low Dose Ketamine | Change in Zanarini Rating Scale for Borderline Personality Disorder | Day 3 | 5.2 score on a scale | Standard Error 1.95 |
Other Pre-specified
Change in Bias Scores on the Implicit Association Tests (IAT) of Death, Escape and Self Harm Imagery.
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.
Time frame: Timepoints: at baseline and 1, 3, 7, 28 days after infusion.
Other Pre-specified
Change in Electroencephalography (EEG) Signal During Behavioral Neuroplasticity Task
measurement of electrical patterns in the brain while subject is performing behavioral task to measure basic neuroplasticity
Time frame: Timepoints: at baseline and 1 and/or 7 days after infusion.
Other Pre-specified
Change in Resting State Electroencephalography (EEG)
measurement of electrical patterns in the brain while subject is at rest with eyes open looking at fixation cross
Time frame: Timepoints: at baseline and 1 and/or 7 days after infusion.