Trial Outcomes & Findings for Ketamine in Borderline Personality Disorder (NCT NCT03395314)

NCT ID: NCT03395314

Last Updated: 2023-06-26

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

22 participants

Primary outcome timeframe

Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

Results posted on

2023-06-26

Participant Flow

Participant milestones

Participant milestones
Measure
Midazolam
Midazolam IV; 0.04mg/kg over 40 minutes Midazolam: 1 single dose of IV midazolam
Low Dose Ketamine
ketamine IV; 0.5 mg/kg over 40 minutes Ketamine: 1 single dose of IV ketamine
Overall Study
STARTED
12
10
Overall Study
COMPLETED
12
10
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Ketamine in Borderline Personality Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Midazolam
n=12 Participants
Midazolam IV; 0.04mg/kg over 40 minutes Midazolam: 1 single dose of IV midazolam
Low Dose Ketamine
n=10 Participants
ketamine IV; 0.5 mg/kg over 40 minutes Ketamine: 1 single dose of IV ketamine
Total
n=22 Participants
Total of all reporting groups
Age, Continuous
35.1 years
STANDARD_DEVIATION 11.4 • n=5 Participants
32.1 years
STANDARD_DEVIATION 10.4 • n=7 Participants
33.7 years
STANDARD_DEVIATION 10.8 • n=5 Participants
Sex: Female, Male
Female
10 Participants
n=5 Participants
8 Participants
n=7 Participants
18 Participants
n=5 Participants
Sex: Female, Male
Male
2 Participants
n=5 Participants
2 Participants
n=7 Participants
4 Participants
n=5 Participants
Race/Ethnicity, Customized
Asian
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Race/Ethnicity, Customized
Arabic
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Race/Ethnicity, Customized
White
10 Participants
n=5 Participants
9 Participants
n=7 Participants
19 Participants
n=5 Participants
Race/Ethnicity, Customized
Hispanic
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Region of Enrollment
United States
12 participants
n=5 Participants
10 participants
n=7 Participants
22 participants
n=5 Participants
Education (years)
16.3 years
STANDARD_DEVIATION 2.7 • n=5 Participants
15.0 years
STANDARD_DEVIATION 2.7 • n=7 Participants
15.7 years
STANDARD_DEVIATION 2.7 • n=5 Participants
Baseline Comorbidities
Major Depressive Disorder
5 Participants
n=5 Participants
5 Participants
n=7 Participants
10 Participants
n=5 Participants
Baseline Comorbidities
Post-Traumatic Stress Disorder
4 Participants
n=5 Participants
3 Participants
n=7 Participants
7 Participants
n=5 Participants
Baseline Comorbidities
Anxiety Disorders
9 Participants
n=5 Participants
7 Participants
n=7 Participants
16 Participants
n=5 Participants
Baseline Comorbidities
Mild Substance Use Disorder
3 Participants
n=5 Participants
3 Participants
n=7 Participants
6 Participants
n=5 Participants
Baseline Comorbidities
Bipolar Disorder
2 Participants
n=5 Participants
1 Participants
n=7 Participants
3 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

Population: Intention to treat.

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.

Outcome measures

Outcome measures
Measure
Midazolam
n=12 Participants
Midazolam IV; 0.04mg/kg over 40 minutes Midazolam: 1 single dose of IV midazolam
Low Dose Ketamine
n=10 Participants
ketamine IV; 0.5 mg/kg over 40 minutes Ketamine: 1 single dose of IV ketamine
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
2.7 units on a scale
Standard Error 0.41
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
0.1 units on a scale
Standard Error 0.41
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
0.5 units on a scale
Standard Error 0.41
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
0.7 units on a scale
Standard Error 0.41
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
0.8 units on a scale
Standard Error 0.41
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
1.3 units on a scale
Standard Error 0.41
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
2.6 units on a scale
Standard Error 0.42

PRIMARY outcome

Timeframe: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

Population: Intention to treat.

Suicide Rating Scale from 1-5; higher numbers indicate increased suicidal thinking.

Outcome measures

Outcome measures
Measure
Midazolam
n=12 Participants
Midazolam IV; 0.04mg/kg over 40 minutes Midazolam: 1 single dose of IV midazolam
Low Dose Ketamine
n=10 Participants
ketamine IV; 0.5 mg/kg over 40 minutes Ketamine: 1 single dose of IV ketamine
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
1.9 score on a scale
Standard Error 0.34
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
0.0 score on a scale
Standard Error 0.34
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
0.0 score on a scale
Standard Error 0.34
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
0.5 score on a scale
Standard Error 0.34
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
0.3 score on a scale
Standard Error 0.34
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
0.8 score on a scale
Standard Error 0.34
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
1.6 score on a scale
Standard Error 0.34

PRIMARY outcome

Timeframe: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

Population: Intention to treat.

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.

Outcome measures

Outcome measures
Measure
Midazolam
n=12 Participants
Midazolam IV; 0.04mg/kg over 40 minutes Midazolam: 1 single dose of IV midazolam
Low Dose Ketamine
n=10 Participants
ketamine IV; 0.5 mg/kg over 40 minutes Ketamine: 1 single dose of IV ketamine
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
1.5 score on a scale
Standard Error 0.23
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
0.2 score on a scale
Standard Error 0.23
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
0.1 score on a scale
Standard Error 0.23
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
0.3 score on a scale
Standard Error 0.23
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
0.5 score on a scale
Standard Error 0.23
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
0.7 score on a scale
Standard Error 0.23
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
1.21 score on a scale
Standard Error 0.23

PRIMARY outcome

Timeframe: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

Population: Intention to treat.

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.

Outcome measures

Outcome measures
Measure
Midazolam
n=12 Participants
Midazolam IV; 0.04mg/kg over 40 minutes Midazolam: 1 single dose of IV midazolam
Low Dose Ketamine
n=10 Participants
ketamine IV; 0.5 mg/kg over 40 minutes Ketamine: 1 single dose of IV ketamine
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
0.3 units on a scale
Standard Error 0.21
Change in Suicidality as Measured by Item 9 on Beck Depression Inventory
baseline
1.16 units on a scale
Standard Error 0.19
1.2 units on a scale
Standard Error 0.21
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
0.1 units on a scale
Standard Error 0.21
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
0.3 units on a scale
Standard Error 0.21
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
0.3 units on a scale
Standard Error 0.21
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
0.3 units on a scale
Standard Error 0.21
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
0.56 units on a scale
Standard Error 0.21

SECONDARY outcome

Timeframe: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

Population: Intention to treat.

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.

Outcome measures

Outcome measures
Measure
Midazolam
n=12 Participants
Midazolam IV; 0.04mg/kg over 40 minutes Midazolam: 1 single dose of IV midazolam
Low Dose Ketamine
n=10 Participants
ketamine IV; 0.5 mg/kg over 40 minutes Ketamine: 1 single dose of IV ketamine
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Baseline
26.75 score on a scale
Standard Error 2.71
28.3 score on a scale
Standard Error 2.97
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
1hr post-infusion
3.66 score on a scale
Standard Error 2.71
6.2 score on a scale
Standard Error 2.97
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Day 1
9.27 score on a scale
Standard Error 2.78
8.2 score on a scale
Standard Error 2.97
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Day 3
11.70 score on a scale
Standard Error 2.78
12.2 score on a scale
Standard Error 2.97
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Day 7
12.5 score on a scale
Standard Error 2.71
12.3 score on a scale
Standard Error 2.97
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Day 14
19.25 score on a scale
Standard Error 2.71
12.9 score on a scale
Standard Error 2.97
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Day 28
17.39 score on a scale
Standard Error 2.85
22.67 score on a scale
Standard Error 3.06

SECONDARY outcome

Timeframe: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

Population: Intention to treat.

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.

Outcome measures

Outcome measures
Measure
Midazolam
n=12 Participants
Midazolam IV; 0.04mg/kg over 40 minutes Midazolam: 1 single dose of IV midazolam
Low Dose Ketamine
n=10 Participants
ketamine IV; 0.5 mg/kg over 40 minutes Ketamine: 1 single dose of IV ketamine
Change in Beck Depression Inventory Score
Baseline
30.75 score on a scale
Standard Error 3.96
34.9 score on a scale
Standard Error 4.34
Change in Beck Depression Inventory Score
1hr post-infusion
11.16 score on a scale
Standard Error 3.96
13.3 score on a scale
Standard Error 4.34
Change in Beck Depression Inventory Score
Day 1
12.41 score on a scale
Standard Error 4.04
12.2 score on a scale
Standard Error 4.34
Change in Beck Depression Inventory Score
Day 3
10.94 score on a scale
Standard Error 4.04
8.9 score on a scale
Standard Error 4.34
Change in Beck Depression Inventory Score
Day 7
11.33 score on a scale
Standard Error 3.96
12.6 score on a scale
Standard Error 4.34
Change in Beck Depression Inventory Score
Day 14
17.41 score on a scale
Standard Error 3.96
14.5 score on a scale
Standard Error 4.34
Change in Beck Depression Inventory Score
Day 28
17.57 score on a scale
Standard Error 4.04
18.73 score on a scale
Standard Error 4.44

SECONDARY outcome

Timeframe: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

Population: Intention to treat.

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.

Outcome measures

Outcome measures
Measure
Midazolam
n=12 Participants
Midazolam IV; 0.04mg/kg over 40 minutes Midazolam: 1 single dose of IV midazolam
Low Dose Ketamine
n=10 Participants
ketamine IV; 0.5 mg/kg over 40 minutes Ketamine: 1 single dose of IV ketamine
Change in Beck Anxiety Inventory Score
Baseline
21.75 score on a scale
Standard Error 2.51
21.7 score on a scale
Standard Error 2.75
Change in Beck Anxiety Inventory Score
1hr post-infusion
4.0 score on a scale
Standard Error 2.51
7.3 score on a scale
Standard Error 2.75
Change in Beck Anxiety Inventory Score
Day 1
7.43 score on a scale
Standard Error 2.57
8.3 score on a scale
Standard Error 2.75
Change in Beck Anxiety Inventory Score
Day 3
5.71 score on a scale
Standard Error 2.71
5.5 score on a scale
Standard Error 2.75
Change in Beck Anxiety Inventory Score
Day 7
7.43 score on a scale
Standard Error 2.57
8.2 score on a scale
Standard Error 2.75
Change in Beck Anxiety Inventory Score
Day 14
8.88 score on a scale
Standard Error 2.57
11.0 score on a scale
Standard Error 2.75
Change in Beck Anxiety Inventory Score
Day 28
6.34 score on a scale
Standard Error 2.65
18.23 score on a scale
Standard Error 2.91

SECONDARY outcome

Timeframe: Timepoints will be baseline and at 1, 3, 7, 14, & 28 days after infusion.

Population: Intention to treat.

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.

Outcome measures

Outcome measures
Measure
Midazolam
n=12 Participants
Midazolam IV; 0.04mg/kg over 40 minutes Midazolam: 1 single dose of IV midazolam
Low Dose Ketamine
n=10 Participants
ketamine IV; 0.5 mg/kg over 40 minutes Ketamine: 1 single dose of IV ketamine
Change in Zanarini Rating Scale for Borderline Personality Disorder
Baseline
14.33 score on a scale
Standard Error 1.78
15.4 score on a scale
Standard Error 1.95
Change in Zanarini Rating Scale for Borderline Personality Disorder
Day 1
3.52 score on a scale
Standard Error 1.81
5.2 score on a scale
Standard Error 1.95
Change in Zanarini Rating Scale for Borderline Personality Disorder
Day 3
5.04 score on a scale
Standard Error 1.81
5.2 score on a scale
Standard Error 1.95
Change in Zanarini Rating Scale for Borderline Personality Disorder
Day 7
5 score on a scale
Standard Error 1.78
6.8 score on a scale
Standard Error 1.95
Change in Zanarini Rating Scale for Borderline Personality Disorder
Day 14
6.75 score on a scale
Standard Error 1.78
7.2 score on a scale
Standard Error 1.95
Change in Zanarini Rating Scale for Borderline Personality Disorder
Day 28
7.16 score on a scale
Standard Error 1.81
11.42 score on a scale
Standard Error 1.99

SECONDARY outcome

Timeframe: Timepoints will be at baseline and 3, 7, 14, 28 days after infusion

Population: Intention to treat.

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.

Outcome measures

Outcome measures
Measure
Midazolam
n=12 Participants
Midazolam IV; 0.04mg/kg over 40 minutes Midazolam: 1 single dose of IV midazolam
Low Dose Ketamine
n=10 Participants
ketamine IV; 0.5 mg/kg over 40 minutes Ketamine: 1 single dose of IV ketamine
Change in Preferred Distance in Stop-distance Paradigm (SDP)
Baseline
18.6 distance in inches
Standard Error 1.97
20.6 distance in inches
Standard Error 2.5
Change in Preferred Distance in Stop-distance Paradigm (SDP)
Day 3
17.3 distance in inches
Standard Error 2.12
17.2 distance in inches
Standard Error 2.5
Change in Preferred Distance in Stop-distance Paradigm (SDP)
Day 7
14.7 distance in inches
Standard Error 2.11
15.5 distance in inches
Standard Error 2.5
Change in Preferred Distance in Stop-distance Paradigm (SDP)
Day 14
19.4 distance in inches
Standard Error 1.97
16.5 distance in inches
Standard Error 2.5
Change in Preferred Distance in Stop-distance Paradigm (SDP)
Day 28
17.2 distance in inches
Standard Error 2.11
19.5 distance in inches
Standard Error 2.63

SECONDARY outcome

Timeframe: Timepoints will be at baseline and 3, 7, 14, 28 days after infusion

Population: Intention to treat.

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.

Outcome measures

Outcome measures
Measure
Midazolam
n=12 Participants
Midazolam IV; 0.04mg/kg over 40 minutes Midazolam: 1 single dose of IV midazolam
Low Dose Ketamine
n=10 Participants
ketamine IV; 0.5 mg/kg over 40 minutes Ketamine: 1 single dose of IV ketamine
Change in Behavior in the Economic Trust Game - Cooperation
Baseline
0.39 proportion of amount returned
Standard Error 0.05
0.38 proportion of amount returned
Standard Error 0.06
Change in Behavior in the Economic Trust Game - Cooperation
Day 3
0.36 proportion of amount returned
Standard Error 0.05
0.42 proportion of amount returned
Standard Error 0.06
Change in Behavior in the Economic Trust Game - Cooperation
Day 7
0.42 proportion of amount returned
Standard Error 0.05
0.29 proportion of amount returned
Standard Error 0.06
Change in Behavior in the Economic Trust Game - Cooperation
Day 14
0.34 proportion of amount returned
Standard Error 0.05
0.39 proportion of amount returned
Standard Error 0.06
Change in Behavior in the Economic Trust Game - Cooperation
Day 28
0.31 proportion of amount returned
Standard Error 0.09
0.31 proportion of amount returned
Standard Error 0.06

SECONDARY outcome

Timeframe: Timepoints will be at baseline and 3, 7, 14, 28 days after infusion

Population: Intention to treat.

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

Outcome measures

Outcome measures
Measure
Midazolam
n=12 Participants
Midazolam IV; 0.04mg/kg over 40 minutes Midazolam: 1 single dose of IV midazolam
Low Dose Ketamine
n=10 Participants
ketamine IV; 0.5 mg/kg over 40 minutes Ketamine: 1 single dose of IV ketamine
Change in Social Adjustment Scale Self Report (SAS-SR) Short Version Score
Baseline
2.86 score on a scale
Standard Error 0.18
2.74 score on a scale
Standard Error 0.20
Change in Social Adjustment Scale Self Report (SAS-SR) Short Version Score
Day 3
2.30 score on a scale
Standard Error 0.19
1.95 score on a scale
Standard Error 0.20
Change in Social Adjustment Scale Self Report (SAS-SR) Short Version Score
Day 7
2.17 score on a scale
Standard Error 0.19
2.02 score on a scale
Standard Error 0.20
Change in Social Adjustment Scale Self Report (SAS-SR) Short Version Score
Day 14
2.58 score on a scale
Standard Error 0.18
2.07 score on a scale
Standard Error 0.20
Change in Social Adjustment Scale Self Report (SAS-SR) Short Version Score
Day 28
2.33 score on a scale
Standard Error 0.19
2.12 score on a scale
Standard Error 0.20

SECONDARY outcome

Timeframe: Timepoints will be at baseline, and post-infusion 1hr, and days 1, 3, 7, 14, & 28.

Population: Intention to treat.

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

Outcome measures

Outcome measures
Measure
Midazolam
n=12 Participants
Midazolam IV; 0.04mg/kg over 40 minutes Midazolam: 1 single dose of IV midazolam
Low Dose Ketamine
n=10 Participants
ketamine IV; 0.5 mg/kg over 40 minutes Ketamine: 1 single dose of IV ketamine
Change in Brief Pain Inventory Score - Intensity
Baseline
6.19 score on a scale
Standard Error 0.93
6.32 score on a scale
Standard Error 1.03
Change in Brief Pain Inventory Score - Intensity
Post-infusion 1hr
5.75 score on a scale
Standard Error 1.64
2.56 score on a scale
Standard Error 2.23
Change in Brief Pain Inventory Score - Intensity
Day 1
6.52 score on a scale
Standard Error 1.34
4.46 score on a scale
Standard Error 2.28
Change in Brief Pain Inventory Score - Intensity
Day 3
6.73 score on a scale
Standard Error 1.61
4.46 score on a scale
Standard Error 2.28
Change in Brief Pain Inventory Score - Intensity
Day 7
9.04 score on a scale
Standard Error 2.22
5.92 score on a scale
Standard Error 1.16
Change in Brief Pain Inventory Score - Intensity
Day 14
3.2 score on a scale
Standard Error 1.33
4.14 score on a scale
Standard Error 1.16
Change in Brief Pain Inventory Score - Intensity
Day 28
6.28 score on a scale
Standard Error 1.62
5.11 score on a scale
Standard Error 1.33

SECONDARY outcome

Timeframe: Timepoints will be at baseline, and post-infusion 1hr, and days 1, 3, 7, 14, & 28.

Population: Intention to treat.

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

Outcome measures

Outcome measures
Measure
Midazolam
n=12 Participants
Midazolam IV; 0.04mg/kg over 40 minutes Midazolam: 1 single dose of IV midazolam
Low Dose Ketamine
n=10 Participants
ketamine IV; 0.5 mg/kg over 40 minutes Ketamine: 1 single dose of IV ketamine
Change in Brief Pain Inventory Score - Interference
Baseline
3.49 score on a scale
Standard Error 1.05
2.94 score on a scale
Standard Error 1.13
Change in Brief Pain Inventory Score - Interference
Post-infusion 1hr
1.22 score on a scale
Standard Error 1.58
0.51 score on a scale
Standard Error 1.94
Change in Brief Pain Inventory Score - Interference
Day 1
4.79 score on a scale
Standard Error 1.34
3.1 score on a scale
Standard Error 2.03
Change in Brief Pain Inventory Score - Interference
Day 3
3.41 score on a scale
Standard Error 1.51
3.1 score on a scale
Standard Error 2.03
Change in Brief Pain Inventory Score - Interference
Day 7
4.06 score on a scale
Standard Error 1.95
4.09 score on a scale
Standard Error 1.36
Change in Brief Pain Inventory Score - Interference
Day 14
2.21 score on a scale
Standard Error 1.36
3.45 score on a scale
Standard Error 1.19
Change in Brief Pain Inventory Score - Interference
Day 28
4.23 score on a scale
Standard Error 1.64
4.52 score on a scale
Standard Error 1.36

SECONDARY outcome

Timeframe: Timepoints: pre- infusion, during infusion +20, +40 minutes, and post-infusion 40 minutes.

Population: Intention to treat.

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.

Outcome measures

Outcome measures
Measure
Midazolam
n=12 Participants
Midazolam IV; 0.04mg/kg over 40 minutes Midazolam: 1 single dose of IV midazolam
Low Dose Ketamine
n=10 Participants
ketamine IV; 0.5 mg/kg over 40 minutes Ketamine: 1 single dose of IV ketamine
Change in Clinician-Administered Dissociative States Scale (CADSS) Score
Baseline (pre-infusion)
5.94 score on a scale
Standard Error 4.11
5.92 score on a scale
Standard Error 3.99
Change in Clinician-Administered Dissociative States Scale (CADSS) Score
20 minutes (during infusion)
5.54 score on a scale
Standard Error 3.46
25.4 score on a scale
Standard Error 3.63
Change in Clinician-Administered Dissociative States Scale (CADSS) Score
40 minutes (during infusion)
9.54 score on a scale
Standard Error 3.46
16.8 score on a scale
Standard Error 3.63
Change in Clinician-Administered Dissociative States Scale (CADSS) Score
80 minutes (post infusion)
1.90 score on a scale
Standard Error 3.46
3.0 score on a scale
Standard Error 3.63

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Midazolam
n=12 Participants
Midazolam IV; 0.04mg/kg over 40 minutes Midazolam: 1 single dose of IV midazolam
Low Dose Ketamine
n=10 Participants
ketamine IV; 0.5 mg/kg over 40 minutes Ketamine: 1 single dose of IV ketamine
Change in Adverse Events
0 Participants
0 Participants

SECONDARY outcome

Timeframe: Timepoints: at baseline and 3, 7, 14, 28 days after infusion.

Population: Intention to treat.

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.

Outcome measures

Outcome measures
Measure
Midazolam
n=12 Participants
Midazolam IV; 0.04mg/kg over 40 minutes Midazolam: 1 single dose of IV midazolam
Low Dose Ketamine
n=10 Participants
ketamine IV; 0.5 mg/kg over 40 minutes Ketamine: 1 single dose of IV ketamine
Change in 'Reading the Mind in the Eyes' Test (RMET) Score
Day 14
29.9 score on a scale
Standard Error 1.11
25.1 score on a scale
Standard Error 1.23
Change in 'Reading the Mind in the Eyes' Test (RMET) Score
Baseline
28.2 score on a scale
Standard Error 1.11
25.6 score on a scale
Standard Error 1.23
Change in 'Reading the Mind in the Eyes' Test (RMET) Score
Day 3
27.6 score on a scale
Standard Error 1.13
27.3 score on a scale
Standard Error 1.23
Change in 'Reading the Mind in the Eyes' Test (RMET) Score
Day 7
29.2 score on a scale
Standard Error 1.11
26.6 score on a scale
Standard Error 1.23
Change in 'Reading the Mind in the Eyes' Test (RMET) Score
Day 28
29.9 score on a scale
Standard Error 1.11
25.4 score on a scale
Standard Error 1.26

SECONDARY outcome

Timeframe: Timepoints: pre-infusion, during infusion +20, +40 minutes, post-infusion +40 minutes

Population: Intention to treat.

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.

Outcome measures

Outcome measures
Measure
Midazolam
n=12 Participants
Midazolam IV; 0.04mg/kg over 40 minutes Midazolam: 1 single dose of IV midazolam
Low Dose Ketamine
n=10 Participants
ketamine IV; 0.5 mg/kg over 40 minutes Ketamine: 1 single dose of IV ketamine
Change in Brief Psychiatric Rating Scale (BPRS) Total Scores
Baseline (pre-infusion)
29.36 score on a scale
Standard Error 2.34
33.79 score on a scale
Standard Error 2.20
Change in Brief Psychiatric Rating Scale (BPRS) Total Scores
20 Minutes (during infusion)
28.18 score on a scale
Standard Error 1.81
38.7 score on a scale
Standard Error 1.90
Change in Brief Psychiatric Rating Scale (BPRS) Total Scores
40 Minutes (during infusion)
28.0 score on a scale
Standard Error 1.81
36.2 score on a scale
Standard Error 1.90
Change in Brief Psychiatric Rating Scale (BPRS) Total Scores
80 Minutes (post infusion)
25.9 score on a scale
Standard Error 1.81
28.2 score on a scale
Standard Error 1.90

SECONDARY outcome

Timeframe: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

Population: Intention to treat.

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.

Outcome measures

Outcome measures
Measure
Midazolam
n=12 Participants
Midazolam IV; 0.04mg/kg over 40 minutes Midazolam: 1 single dose of IV midazolam
Low Dose Ketamine
n=10 Participants
ketamine IV; 0.5 mg/kg over 40 minutes Ketamine: 1 single dose of IV ketamine
Change in Beck Suicide Scale Total Score
Baseline
7.66 score on a scale
Standard Error 1.75
11.5 score on a scale
Standard Error 1.91
Change in Beck Suicide Scale Total Score
1hr post-infusion
3.5 score on a scale
Standard Error 1.75
4.1 score on a scale
Standard Error 1.91
Change in Beck Suicide Scale Total Score
Day 1
3.13 score on a scale
Standard Error 1.79
3.3 score on a scale
Standard Error 1.91
Change in Beck Suicide Scale Total Score
Day 3
2.92 score on a scale
Standard Error 1.79
3.9 score on a scale
Standard Error 1.91
Change in Beck Suicide Scale Total Score
Day 7
3.08 score on a scale
Standard Error 1.75
4.6 score on a scale
Standard Error 1.91
Change in Beck Suicide Scale Total Score
Day 14
5.66 score on a scale
Standard Error 1.75
5.4 score on a scale
Standard Error 1.91
Change in Beck Suicide Scale Total Score
Day 28
4.51 score on a scale
Standard Error 1.79
7.12 score on a scale
Standard Error 1.97

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Outcome measures

Outcome data not reported

Adverse Events

Midazolam

Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths

Low Dose Ketamine

Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Midazolam
n=12 participants at risk
Midazolam IV; 0.04mg/kg over 40 minutes Midazolam: 1 single dose of IV midazolam
Low Dose Ketamine
n=10 participants at risk
ketamine IV; 0.5 mg/kg over 40 minutes Ketamine: 1 single dose of IV ketamine
Nervous system disorders
Vivid dreams
58.3%
7/12 • Number of events 13 • Uo to 28 days
60.0%
6/10 • Number of events 23 • Uo to 28 days
Nervous system disorders
Blurry/double vision
16.7%
2/12 • Number of events 3 • Uo to 28 days
30.0%
3/10 • Number of events 9 • Uo to 28 days
Musculoskeletal and connective tissue disorders
Jerky muscle movements
8.3%
1/12 • Number of events 2 • Uo to 28 days
30.0%
3/10 • Number of events 10 • Uo to 28 days
Gastrointestinal disorders
Nausea or vomiting
25.0%
3/12 • Number of events 10 • Uo to 28 days
40.0%
4/10 • Number of events 12 • Uo to 28 days
Gastrointestinal disorders
Diarrhea
16.7%
2/12 • Number of events 6 • Uo to 28 days
10.0%
1/10 • Number of events 1 • Uo to 28 days
Nervous system disorders
Hallucinations/Misperceptions
0.00%
0/12 • Uo to 28 days
10.0%
1/10 • Number of events 1 • Uo to 28 days
Nervous system disorders
Headaches
33.3%
4/12 • Number of events 8 • Uo to 28 days
10.0%
1/10 • Number of events 2 • Uo to 28 days
Nervous system disorders
Fatigue/Unsteadiness
33.3%
4/12 • Number of events 6 • Uo to 28 days
20.0%
2/10 • Number of events 2 • Uo to 28 days
Endocrine disorders
Increased thirst
0.00%
0/12 • Uo to 28 days
10.0%
1/10 • Number of events 1 • Uo to 28 days
Nervous system disorders
Body pain
0.00%
0/12 • Uo to 28 days
10.0%
1/10 • Number of events 3 • Uo to 28 days

Additional Information

Sarah Fineberg, MD, PhD

Yale School of Medicine

Phone: (203) 974-7265

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place