Trial Outcomes & Findings for Effect of Ketamine on Laboratory-induced Stress in Healthy Subjects (NCT NCT04173962)

NCT ID: NCT04173962

Last Updated: 2022-05-10

Results Overview

Change from pre- to post-TSST in The Profile of Mood States - Bipolar Version (POMS - Bi) scale measures moods and feelings primarily in clinical rather than nonclinical settings. The POMS-Bi consists of 72 adjectives that form six bipolar sub-scale scores (Composed - Anxious, Clear - Confused, Confident - Unsure, Agreeable - Hostile, Energetic - Tired, Elated - Depressed). Each of the 12 adjectives within each subscale is rated on a 4-point Likert scale with anchors of 0 = "much unlike this," 1 = "slightly unlike this," 2 = "slightly like this," and 3 = "much like this." The Composed-Anxious Subscale score is the sum of positive minus the sum of negative responses plus a constant of 18. The subscale score range is from 0 to 36. Higher score indicates higher functioning. Each subscale is separate and there is no overall score.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 24 participants
• Primary outcome timeframe: baseline and 1 week after infusion
• Results posted on: 2022-05-10

Participant Flow

Study conducted between August 2019 and March 2021 at the Icahn School of Medicine at Mount Sinai Depression and Anxiety Center for Discovery and Treatment.

Participant milestones

Measure	Ketamine Group One 0.5mg/kg intravenous dose of ketamine Ketamine: administered 1 week prior to a laboratory-induced stress	Midazolam Group One 0.045mg/kg intravenous dose of midazolam Midazolam: administered 1 week prior to a laboratory-induced stress
Overall Study STARTED	12	12
Overall Study COMPLETED	12	12
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effect of Ketamine on Laboratory-induced Stress in Healthy Subjects

Baseline characteristics by cohort

Measure	Ketamine Group n=12 Participants One 0.5mg/kg intravenous dose of ketamine Ketamine: administered 1 week prior to a laboratory-induced stress	Midazolam Group n=12 Participants One 0.045mg/kg intravenous dose of midazolam Midazolam: administered 1 week prior to a laboratory-induced stress	Total n=24 Participants Total of all reporting groups
Age, Continuous	28.4 years STANDARD_DEVIATION 7.7 • n=5 Participants	28.2 years STANDARD_DEVIATION 7.9 • n=7 Participants	28.3 years STANDARD_DEVIATION 7.6 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	9 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: baseline and 1 week after infusion

Change from pre- to post-TSST in The Profile of Mood States - Bipolar Version (POMS - Bi) scale measures moods and feelings primarily in clinical rather than nonclinical settings. The POMS-Bi consists of 72 adjectives that form six bipolar sub-scale scores (Composed - Anxious, Clear - Confused, Confident - Unsure, Agreeable - Hostile, Energetic - Tired, Elated - Depressed). Each of the 12 adjectives within each subscale is rated on a 4-point Likert scale with anchors of 0 = "much unlike this," 1 = "slightly unlike this," 2 = "slightly like this," and 3 = "much like this." The Composed-Anxious Subscale score is the sum of positive minus the sum of negative responses plus a constant of 18. The subscale score range is from 0 to 36. Higher score indicates higher functioning. Each subscale is separate and there is no overall score.

Outcome measures

Measure	Ketamine Group n=12 Participants One 0.5mg/kg intravenous dose of ketamine Ketamine: administered 1 week prior to a laboratory-induced stress	Midazolam Group n=12 Participants One 0.045mg/kg intravenous dose of midazolam Midazolam: administered 1 week prior to a laboratory-induced stress
Change in The Profile of Mood States - Bipolar Version (POMS - Bi) Composed-Anxious Subscale	-6.8 score on a scale Standard Deviation 5.8	-11.9 score on a scale Standard Deviation 8.6

SECONDARY outcome

Timeframe: baseline and 1 week after infusion

Change from pre- to post-TSST in salivary cortisol level. Salivary cortisol level to assess effect on the hypothalamic-pituitary-adrenal axis (HPA axis).

Outcome measures

Measure	Ketamine Group n=12 Participants One 0.5mg/kg intravenous dose of ketamine Ketamine: administered 1 week prior to a laboratory-induced stress	Midazolam Group n=12 Participants One 0.045mg/kg intravenous dose of midazolam Midazolam: administered 1 week prior to a laboratory-induced stress
Change in Salivary Cortisol	0.1 ug/dL Standard Deviation 0.1	0.0 ug/dL Standard Deviation 0.1

SECONDARY outcome

Timeframe: baseline and 1 week after infusion

Change from pre- to post-TSST in Cardiovascular response to stressor during assessment visit

Outcome measures

Measure	Ketamine Group n=12 Participants One 0.5mg/kg intravenous dose of ketamine Ketamine: administered 1 week prior to a laboratory-induced stress	Midazolam Group n=12 Participants One 0.045mg/kg intravenous dose of midazolam Midazolam: administered 1 week prior to a laboratory-induced stress
Change in Systolic Blood Pressure	4.3 mmHg Standard Deviation 11.32	12.9 mmHg Standard Deviation 11.88

SECONDARY outcome

Timeframe: baseline and 1 week after infusion

Change from pre- to post-TSST in Cardiovascular response to stressor during assessment visit

Outcome measures

Measure	Ketamine Group n=12 Participants One 0.5mg/kg intravenous dose of ketamine Ketamine: administered 1 week prior to a laboratory-induced stress	Midazolam Group n=12 Participants One 0.045mg/kg intravenous dose of midazolam Midazolam: administered 1 week prior to a laboratory-induced stress
Change in Diastolic Blood Pressure	4.17 mmHg Standard Deviation 7.12	6.58 mmHg Standard Deviation 6.6

SECONDARY outcome

Timeframe: baseline and 1 week after infusion

Change from pre- to post-TSST in Cardiovascular response to stressor during assessment visit

Outcome measures

Measure	Ketamine Group n=12 Participants One 0.5mg/kg intravenous dose of ketamine Ketamine: administered 1 week prior to a laboratory-induced stress	Midazolam Group n=12 Participants One 0.045mg/kg intravenous dose of midazolam Midazolam: administered 1 week prior to a laboratory-induced stress
Change in Heart Rate	-0.33 beats per minute (bpm) Standard Deviation 6.8	3.83 beats per minute (bpm) Standard Deviation 7.5

SECONDARY outcome

Timeframe: baseline and 1 week after infusion

Change from pre- to post-TSST in Salivary alpha-amylase level to assess effect on the adrenaline-noradrenaline axis (ANS axis).

Outcome measures

Measure	Ketamine Group n=12 Participants One 0.5mg/kg intravenous dose of ketamine Ketamine: administered 1 week prior to a laboratory-induced stress	Midazolam Group n=12 Participants One 0.045mg/kg intravenous dose of midazolam Midazolam: administered 1 week prior to a laboratory-induced stress
Change in Salivary Alpha-amylase Level	109.0 U/mL Standard Deviation 144.4	141.7 U/mL Standard Deviation 106.6

SECONDARY outcome

Timeframe: baseline and 1 week after infusion

Change from pre- to post-TSST in The Positive and Negative Affect Scale (PANAS) measures both positive and negative affect and is utilized within clinical and non-clinical populations. The PANAS is a 20-item instrument, each item is scored on a 5-likert scale from 1 (very slightly or not at all) to 5 (extremely). Positive Affect Score - total score from 10-50, with higher score indicating higher levels of positive affect. Negative Affect Score - total score from 10-50, with lower scores representing lower levels of negative affect.

Outcome measures

Measure	Ketamine Group n=12 Participants One 0.5mg/kg intravenous dose of ketamine Ketamine: administered 1 week prior to a laboratory-induced stress	Midazolam Group n=12 Participants One 0.045mg/kg intravenous dose of midazolam Midazolam: administered 1 week prior to a laboratory-induced stress
Change in Positive and Negative Affect Scale (PANAS) Negative Affect Score	2.2 score on a scale Standard Deviation 3.7	4.6 score on a scale Standard Deviation 4.9
Change in Positive and Negative Affect Scale (PANAS) Positive Affect Score	-2.2 score on a scale Standard Deviation 10.1	1.2 score on a scale Standard Deviation 6.5

SECONDARY outcome

Timeframe: baseline and 1 week after infusion

Change from pre- to post-TSST in The Visual Analog Scales are scored in millimeters from the left-hand side of a 100-mm line to a perpendicular mark made by the patient at a point corresponding to the apparent magnitude of the feeling state. Full range: 0 ("not at all") to 100 ("most ever"), with higher score indicating poorer health status. The VAS-Stressed prompts participants to rate their level of stress in that exact moment on the visual analog scale.

Outcome measures

Measure	Ketamine Group n=12 Participants One 0.5mg/kg intravenous dose of ketamine Ketamine: administered 1 week prior to a laboratory-induced stress	Midazolam Group n=12 Participants One 0.045mg/kg intravenous dose of midazolam Midazolam: administered 1 week prior to a laboratory-induced stress
Change in Visual Analog Scale: Stressed (VAS-Stressed)	12.8 score on a scale Standard Deviation 11.6	12.1 score on a scale Standard Deviation 22.3

SECONDARY outcome

Timeframe: baseline and 1 week after infusion

Change from pre- to post-TSST in Beck Anxiety Inventory (BAI). This is a 21-question multiple-choice self-report inventory that is used for measuring the severity of anxiety in adults. The questions used in this measure ask about common symptoms of anxiety (such as numbness and tingling, sweating not due to heat, and fear of the worst happening). It is designed for individuals who are of 17 years of age or older and takes 5 to 10 minutes to complete. Total score range of 0-63, with higher score indicating more severe anxiety symptoms.

Outcome measures

Measure	Ketamine Group n=12 Participants One 0.5mg/kg intravenous dose of ketamine Ketamine: administered 1 week prior to a laboratory-induced stress	Midazolam Group n=12 Participants One 0.045mg/kg intravenous dose of midazolam Midazolam: administered 1 week prior to a laboratory-induced stress
Change in Beck Anxiety Inventory (BAI)	0.8 score on a scale Standard Deviation 1.4	2.6 score on a scale Standard Deviation 4.1

Adverse Events

Ketamine Group

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Midazolam Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Ketamine Group n=12 participants at risk One 0.5mg/kg intravenous dose of ketamine Ketamine: administered 1 week prior to a laboratory-induced stress	Midazolam Group n=12 participants at risk One 0.045mg/kg intravenous dose of midazolam Midazolam: administered 1 week prior to a laboratory-induced stress
Nervous system disorders Dizziness	16.7% 2/12 • 1 week	0.00% 0/12 • 1 week
Nervous system disorders Headache	16.7% 2/12 • 1 week	0.00% 0/12 • 1 week
Musculoskeletal and connective tissue disorders Muscle Weakness	8.3% 1/12 • 1 week	0.00% 0/12 • 1 week

Additional Information

Dr. James Murrough

Icahn School of Medicine at Mount Sinai

Phone: 212-585-4640

Email: james.murrough@mssm.edu

Results disclosure agreements

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