Healthy VolunteersPhase 2NCT04173962
Effect of Ketamine on Laboratory-induced Stress in Healthy Subjects
A Phase 2 study testing Ketamine and Midazolam in people with Healthy Volunteers, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial summary
The objective of this study is to examine the effect of a single IV dose of ketamine (0.5 mg/kg) on laboratory-induced stress in healthy participants. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Ketamine and Midazolam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Aug 2019to 18 Mar 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Males and females aged 18-45 years;
- Does not meet for any current or past psychiatric diagnoses as defined by DSM-V criteria;
- Participants must have a level of understanding of the English language sufficient to agree to all tests and examinations required by the study and must be able to participate fully in the informed consent process.
Who cannot join
- Any current or lifetime psychiatric disorder as determined by the Structured Clinical Interview for DSM-V Axis Disorders (SCID-5);
- Concomitant use of any medication with central nervous system activity, including treatment with antidepressants (classified as SSRIs, SNRIs, Atypical Antidepressants, TCAs);
- Any unstable medical illnesses including hepatic, renal impairment, gastroenterologic (including gastro-esophageal reflux disease), respiratory (including obstructive sleep apnea, or history of difficulty with airway management during previous anesthetics), cardiovascular (including ischemic heart disease and uncontrolled hypertension), endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;
- Hypertension (systolic BP >160 mm Hg or diastolic BP >90 mm Hg) at screening or immediately prior to treatment with ketamine/midazolam;
- Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG; clinically significant is defined by an abnormality that suggests a disease and/or organ toxicity that is new or has worsened from screening, or if the abnormality is of a degree that requires additional active management (e.g., further diagnostic investigation).
- Patients who have a positive urine toxicology test for illicit substances at screening and on the treatment day.
- Previous recreational use of PCP or ketamine.
- Subjects who have received ketamine in the past.
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: Effect of Ketamine on Laboratory-induced Stress in Healthy Subjects: A Proof-of-Concept Translational Study
The objective of this study is to examine the effect of a single IV dose of ketamine (0.5 mg/kg) on laboratory-induced stress in healthy participants.
Read the detailed description
Stress exposure is one of the greatest risk factors for psychiatric illnesses like major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). Stress resilience is the ability to experience stress without developing psychopathology. Enhancing stress resilience in at-risk populations could potentially protect against the development of stress-induced psychiatric disorders. Despite this, no resilience-enhancing pharmaceuticals have been identified yet. Pre-clinical studies showed that the administration of the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine one week before an acute stress prevents the developing of depressive-like behavior in animals. In this project the study team proposes a pilot study to test if this stress prophylactic effect of ketamine applies also to humans. Ketamine will be compared to an active placebo control condition, the anesthetic midazolam, in a sample of healthy volunteers. The specific aims of this project are to test the effect of ketamine administered 1-week prior a laboratory-induced stress (1) on the positive and negative affect as measured with the Profile of Mood States (POMS) - Bipolar and (2) on the hypothalamic-pituitary-adrenal axis (HPA axis), adrenaline-noradrenaline axis (ANS axis), and self-reports of anxiety. The study team expects that subjects treated with ketamine, compared to midazolam, will experience reduced symptoms of negative affect and anxiety and a blunted hormonal response to an acute stress.
- Conditions
- Healthy Volunteers
- Keywords
- Ketamine, Resilience, Stress, Healthy Volunteers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
administered 1 week prior to a laboratory-induced stress
MidazolamDrug
administered 1 week prior to a laboratory-induced stress
| Study group | Role | What they receive |
|---|---|---|
| Ketamine group | Experimental | One 0.5mg/kg intravenous dose of ketamine Receives: Drug: Ketamine |
| Midazolam group | Active comparator | One 0.045mg/kg intravenous dose of midazolam Receives: Drug: Midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in The Profile of Mood States - Bipolar Version (POMS - Bi) Composed-Anxious Subscale
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.
Measured: baseline and 1 week after infusion
Secondary outcomes (8)
Change in Salivary Cortisol
Change from pre- to post-TSST in salivary cortisol level. Salivary cortisol level to assess effect on the hypothalamic-pituitary-adrenal axis (HPA axis).
Measured: baseline and 1 week after infusion
Change in Systolic Blood Pressure
Change from pre- to post-TSST in Cardiovascular response to stressor during assessment visit
Measured: baseline and 1 week after infusion
Change in Diastolic Blood Pressure
Change from pre- to post-TSST in Cardiovascular response to stressor during assessment visit
Measured: baseline and 1 week after infusion
Change in Heart Rate
Change from pre- to post-TSST in Cardiovascular response to stressor during assessment visit
Measured: baseline and 1 week after infusion
Change in Salivary Alpha-amylase Level
Change from pre- to post-TSST in Salivary alpha-amylase level to assess effect on the adrenaline-noradrenaline axis (ANS axis).
Measured: baseline and 1 week after infusion
Change in Positive and Negative Affect Scale (PANAS)
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.
Measured: baseline and 1 week after infusion
Change in Visual Analog Scale: Stressed (VAS-Stressed)
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.
Measured: baseline and 1 week after infusion
Change in Beck Anxiety Inventory (BAI)
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.
Measured: baseline and 1 week after infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2019
- Study start8 Aug 2019
- Primary completion18 Mar 2021
- Study completion18 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants are assigned to one of two groups in parallel during the duration of the study: the ketamine arm or the midazolam arm.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, James Murrough, Icahn School of Medicine at Mount Sinai
- Investigators
- James Murrough, MD, PhD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04173962
- Sponsor's protocol ID
- GCO 17-2440
- Status last verified
- Apr 2022
- First submitted
- 21 Nov 2019
- Last updated
- 10 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
O'Halloran PD, Murphy GC, Webster KE. Reliability of the bipolar form of the profile of mood states using an alternative test protocol. Psychol Rep. 2004 Oct;95(2):459-63. doi: 10.2466/pr0.95.2.459-463.
PubMed 15587208Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol. 1988 Dec;56(6):893-7. doi: 10.1037//0022-006x.56.6.893. No abstract available.
PubMed 3204199Crawford JR, Henry JD. The positive and negative affect schedule (PANAS): construct validity, measurement properties and normative data in a large non-clinical sample. Br J Clin Psychol. 2004 Sep;43(Pt 3):245-65. doi: 10.1348/0144665031752934.
PubMed 15333231
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Ketamine on Laboratory-induced Stress in Healthy Subjects: A Proof-of-Concept Translational Study
- ClinicalTrials.gov ID
- NCT04173962
- Acronym / sponsor ID
- GCO 17-2440
- Conditions
- Healthy Volunteers
- Keywords
- Ketamine, Resilience, Stress, Healthy Volunteers
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Study start
- 8 Aug 2019 (actual)
- Primary completion
- 18 Mar 2021 (actual)
- Study completion
- 18 Mar 2021 (actual)
- First posted
- 22 Nov 2019 (actual)
- Results
- Posted 10 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study is to examine the effect of a single IV dose of ketamine (0.5 mg/kg) on laboratory-induced stress in healthy participants.
Detailed description
Stress exposure is one of the greatest risk factors for psychiatric illnesses like major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). Stress resilience is the ability to experience stress without developing psychopathology. Enhancing stress resilience in at-risk populations could potentially protect against the development of stress-induced psychiatric disorders. Despite this, no resilience-enhancing pharmaceuticals have been identified yet. Pre-clinical studies showed that the administration of the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine one week before an acute stress prevents the developing of depressive-like behavior in animals. In this project the study team proposes a pilot study to test if this stress prophylactic effect of ketamine applies also to humans. Ketamine will be compared to an active placebo control condition, the anesthetic midazolam, in a sample of healthy volunteers. The specific aims of this project are to test the effect of ketamine administered 1-week prior a laboratory-induced stress (1) on the positive and negative affect as measured with the Profile of Mood States (POMS) - Bipolar and (2) on the hypothalamic-pituitary-adrenal axis (HPA axis), adrenaline-noradrenaline axis (ANS axis), and self-reports of anxiety. The study team expects that subjects treated with ketamine, compared to midazolam, will experience reduced symptoms of negative affect and anxiety and a blunted hormonal response to an acute stress.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants are assigned to one of two groups in parallel during the duration of the study: the ketamine arm or the midazolam arm.
| Arm | Type | Receives |
|---|---|---|
| Ketamine group | Experimental | Drug: KetamineOne 0.5mg/kg intravenous dose of ketamine |
| Midazolam group | Active comparator | Drug: MidazolamOne 0.045mg/kg intravenous dose of midazolam |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Males and females aged 18-45 years;
- Does not meet for any current or past psychiatric diagnoses as defined by DSM-V criteria;
- Participants must have a level of understanding of the English language sufficient to agree to all tests and examinations required by the study and must be able to participate fully in the informed consent process.
Key exclusion criteria (8 listed)
- Any current or lifetime psychiatric disorder as determined by the Structured Clinical Interview for DSM-V Axis Disorders (SCID-5);
- Concomitant use of any medication with central nervous system activity, including treatment with antidepressants (classified as SSRIs, SNRIs, Atypical Antidepressants, TCAs);
- Any unstable medical illnesses including hepatic, renal impairment, gastroenterologic (including gastro-esophageal reflux disease), respiratory (including obstructive sleep apnea, or history of difficulty with airway management during previous anesthetics), cardiovascular (including ischemic heart disease and uncontrolled hypertension), endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;
- Hypertension (systolic BP >160 mm Hg or diastolic BP >90 mm Hg) at screening or immediately prior to treatment with ketamine/midazolam;
- Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG; clinically significant is defined by an abnormality that suggests a disease and/or organ toxicity that is new or has worsened from screening, or if the abnormality is of a degree that requires additional active management (e.g., further diagnostic investigation).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketamineadministered 1 week prior to a laboratory-induced stress | Drug | Ketamine group |
| Midazolamadministered 1 week prior to a laboratory-induced stress | Drug | Midazolam group |
Primary outcome
Change in The Profile of Mood States - Bipolar Version (POMS - Bi) Composed-Anxious Subscale
Time frame: 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.
8 secondary outcomes
Change in Salivary Cortisol
Time frame: baseline and 1 week after infusion
Change in Systolic Blood Pressure
Time frame: baseline and 1 week after infusion
Change in Diastolic Blood Pressure
Time frame: baseline and 1 week after infusion
Change in Heart Rate
Time frame: baseline and 1 week after infusion
Change in Salivary Alpha-amylase Level
Time frame: baseline and 1 week after infusion
Change in Positive and Negative Affect Scale (PANAS)
Time frame: baseline and 1 week after infusion
Change in Visual Analog Scale: Stressed (VAS-Stressed)
Time frame: baseline and 1 week after infusion
Change in Beck Anxiety Inventory (BAI)
Time frame: baseline and 1 week after infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15587208O'Halloran PD, Murphy GC, Webster KE. Reliability of the bipolar form of the profile of mood states using an alternative test protocol. Psychol Rep. 2004 Oct;95(2):459-63. doi: 10.2466/pr0.95.2.459-463.
- Background: PubMed 3204199Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol. 1988 Dec;56(6):893-7. doi: 10.1037//0022-006x.56.6.893. No abstract available.
- Background: PubMed 15333231Crawford JR, Henry JD. The positive and negative affect schedule (PANAS): construct validity, measurement properties and normative data in a large non-clinical sample. Br J Clin Psychol. 2004 Sep;43(Pt 3):245-65. doi: 10.1348/0144665031752934.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Murrough, MD, PhD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ketamine and Midazolam in people with Healthy Volunteers, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in The Profile of Mood States - Bipolar Version (POMS - Bi) Composed-Anxious Subscale (time frame: baseline and 1 week after infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04173962, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2022.