Clinical trial NCT04173962: Effect of Ketamine on Laboratory-induced Stress in Healthy Subjects
Official title: Effect of Ketamine on Laboratory-induced Stress in Healthy Subjects: A Proof-of-Concept Translational Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Healthy Volunteers
Keywords: Ketamine
Resilience
Stress
Healthy Volunteers
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2019-11-22
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: PREVENTION

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change in The Profile of Mood States - Bipolar Version (POMS - Bi) Composed-Anxious Subscale
timeFrame: baseline and 1 week after infusion
Secondary outcomes:
measure: Change in Salivary Cortisol
timeFrame: baseline and 1 week after infusion
measure: Change in Systolic Blood Pressure
timeFrame: baseline and 1 week after infusion
measure: Change in Diastolic Blood Pressure
timeFrame: baseline and 1 week after infusion
measure: Change in Heart Rate
timeFrame: baseline and 1 week after infusion
measure: Change in Salivary Alpha-amylase Level
timeFrame: baseline and 1 week after infusion
measure: Change in Positive and Negative Affect Scale (PANAS)
timeFrame: baseline and 1 week after infusion
measure: Change in Visual Analog Scale: Stressed (VAS-Stressed)
timeFrame: baseline and 1 week after infusion
measure: Change in Beck Anxiety Inventory (BAI)
timeFrame: baseline and 1 week after infusion
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: James Murrough, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Beck 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.
citation: Crawford 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.