Clinical trial NCT02378415: Subanesthetic IV Bolus Ketamine in the Treatment of Acute Depression
Official title: Subanesthetic IV Bolus Ketamine in the Treatment of Acute Depression
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Acute Depression
Keywords: Depression
Lead sponsor: United States Naval Medical Center, San Diego
Sponsor class: FED
First posted: 2015-03-04
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective of this double-blinded placebo-controlled pilot study is to determine whether a single sub-anesthetic rapid IV bolus dose of ketamine administered to acutely depressed patients with or without suicidality has a significant rapid antidepressant effect in the acutely depressed population. The study will pursue as a primary outcome measure whether a significant reduction in depressive symptoms, as assessed by the BSS and BHS, occurs shortly after administration of ketamine at 40, 80, 120, and 240 minutes. A secondary outcome measure will be assessed to determine whether this single infusion of ketamine has a sustained reduction in depressive symptoms within 2-weeks post-infusion with a reduction in BDI score. Suicidal ideation will also be assessed for determination of any reduction and sustained reduction post infusion by assessment of the Beck Suicidal Ideation Scale (BSS), Beck Hopelessness Scale (BHS) and Beck Depression Inventory (BDI) at similar intervals.

Detailed description: A determination for hospital admittance by a consulting psychiatrist will be made prior to study participation. Only those persons being admitted to the psychiatric ward will be eligible to enroll in this study. After consenting to participate in the trial and meeting inclusion criteria for this study (to include a baseline BDI, BSS, and BHS), voluntarily presenting acutely depressed patients, with or without suicidal ideation, will be randomized into two groups and administered standard of care treatment with intravenous ketamine (0.2mg/kg over 1-2 minutes) or standard of care treatment with intravenous normal saline (equal volume to ketamine dose). All prepared study solutions will be mixed and administered by ED staff and/or nursing staff as per the existing NMCSD ED protocols. All subjects will be blinded to the treatment given, either an IV bolus dose of ketamine at 0.2-mg/kg over 1-2 minutes or a placebo solution composed of an equal IV bolus dose (by overall volume) of 0.9 normal saline solution will be administered. Thereafter, all patients will be evaluated clinically with a BSS, BHS, and BDI at 40, 80, 120, and 240 minutes. All study participants will be monitored medically in the ED for at least the full 240-minute protocol and once declared medically clear, in accordance with standard of care practices by the ED providers, will be transferred to the inpatient psychiatric ward for further monitoring for at least 24-hours prior to discharge from the hospital. All enrolled patients will be administered another BSS, BHS, and BDI prior to discharge from the hospital. The length of hospital stay will also be recorded for further analysis, but will not be considered a secondary outcome measure for this study. Psychiatric determination for discharge from the hospital will be based on clinical assessment, presentation history, and hospital course and is not considered an outcome measure for this study. All patients included in this study will be re-assessed within 2 weeks with another BSS, BHS, and BDI for determination of sustainability of effects. Appropriate follow-up care with a psychiatrist will be afforded to all study participants after discharge from the hospital. Additionally, should any severe adverse side effects develop; the treatment administered to enrolled patients may be un-blinded by a third-party shift medical monitor (i.e. the Charge Nurse) on request from the emergency room provider. Additionally, given the potential psychotropic effects of ketamine and to assure that patients are sufficiently monitored and appropriately medically cleared, all participants in the study will be required to remain under clinical observation in the emergency room prior to transfer to the psychiatric ward for, at least, the full 4-hour treatment cycle or longer as clinically indicated. All participants in this study will only be allowed to enroll in this study and undergo this protocol's treatment once.

Eligibility criteria: Inclusion Criteria:

1. BSS greater than 4
2. BHS greater than 8
3. BDI greater than 19
4. Ability to give informed consent.
5. Active Duty military status.
6. Verified negative qualitative pregnancy test.
7. All participants must be accepted for psychiatric admission to the hospital PRIOR to consideration for enrollment in this study.

Exclusion Criteria:

1. Psychosis or Bipolar Disorder.
2. Pregnancy
3. Involuntary Status on presentation to the ED.
4. UDS positive for illicit drugs of abuse.
5. Blood Alcohol level greater than zero.
6. Previous enrollees in this treatment protocol will be excluded from repeat participation.
7. Any patient brought for command directed psychiatric evaluation.
8. Specific contraindications to the use of ketamine are as follows and under such circumstances or conditions, personnel with the following should be excluded from participation in this study:

   1. Patients with elevated intracranial pressure, uncontrolled hypertension, coronary artery disease, aneurysms, thyrotoxicosis, CHF, a recent history of head or eye injury, or angina.
   2. All personnel in whom a significant elevation of blood pressure would constitute a serious hazard to their overall health and well-being.
   3. Patients currently utilizing the following medications: conivaptan, Disatinib, peginterferon alfa-2b, quazepam, tocilizumab

Primary outcomes:
measure: Suicidality
timeFrame: Baseline
Secondary outcomes:
measure: Depression
timeFrame: Baseline, 40-minutes, 80-minutes, 120-minutes, 240-minutes, exit at discharge, and at follow-up within 2-weeks
measure: Hopelessness
timeFrame: Baseline, 40-minutes, 80-minutes, 120-minutes, 240-minutes, exit at discharge, and at follow-up within 2-weeks
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Naval Medical Center San Diego
state: California
Study officials:
affiliation: United States Naval Medical Center, San Diego
name: Robert E Lovern, MD
role: PRINCIPAL_INVESTIGATOR
References: