A Study of Ketamine Infusions to Treat Clinically-depressed ICU Patients

Study Overview
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Brief Summary
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The purpose of this research is to study the effects of intravenous ketamine infusions for the treatment of patients with depressive symptoms in intensive care unit (ICU).

Official Title
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A Phase II Randomized, Double Blind, Placebo-Controlled Study Evaluating the Effects of Ketamine Infusions in Clinically Depressed ICU Patients

Conditions
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Depression

Intervention / Treatment
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* Drug: Ketamine Hydrochloride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has been in the Mayo Clinic Florida ICU for the past 1 week. PHQ-9 score of 10 or higher. One of the following diagnoses: acute myocardial infarction; acute renal failure; chronic obstructive pulmonary disease (COPD); congestive heart failure; end-stage liver disease; patients requiring intra-aortic balloon pump (IABP) therapy or continuous renal replacement therapy (CRRT); post-bone marrow transplant; acute Hypoxemic Respiratory Failure; acute or chronic hypoxemic respiratory failure; pre- or post- lung, liver or heart transplant or surgical overflows (such as abdominal aortic aneurysm, thoracotomy or tracheostomy). Exclusion Criteria: Poor vital sign stability hypoxia: O2 < 95%, hypotension: SBP < 90 hypertension: SBP > 180. Heart rate: < 50 or > 120, or Respiratory Rate: < 10 or > 30. Altered mental status. Patient is unwilling to participate or provide informed consent. Any allergy to ketamine or diphenhydramine. Patient is female of child-bearing age and unwilling to provide urine or blood for HCG analysis. Pregnant or breastfeeding. Presence of intracranial mass or vascular lesion. Presence of a history of psychosis or hallucinations (as assessed by electronic chart review). Weight greater than 115 kg or less than 45kg. History of increased intracranial pressure/hypertensive hydrocephalus or increased intraocular pressure. Patient is acutely psychotic. Provider feels that patient currently or likely will require chemical and/or physical restraints. History of prolonged QT-interval. Current treatment includes any medication known to affect the N-methyl-D-aspartate receptor system (e.g., lamotrigine, acamprosate, memantine, riluzole, or lithium). Patient in withdrawal from substance abuse or who have used hallucinogens (including cannabis) in the last month for any indication, as determined by the clinical interview and urine drug screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine Group<br>Adult patients who have been in the Mayo Clinic Florida ICU for one week with moderate or severe depression will receive intravenous (IV) ketamine | Drug: Ketamine Hydrochloride<br>* Intravenous 0.5 mg/kg infusions of ketamine for three consecutive days, 24 hours apart, with no more than 1mg/kg or 60 mg/day regardless of body weight<br>* Other names: Ketalar;|
| Placebo Comparator: Placebo Group<br>Adult patients who have been in the Mayo Clinic Florida ICU for one week with moderate or severe depression will receive intravenous (IV) placebo | Drug: Placebo<br>* Intravenous 0.9% saline infusions for three consecutive days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in depressive symptoms | Evaluated by Patient Health Questionnaire-9 (PHQ-9) used to assess degree of depression severity rating symptoms on a scale of 0=not at all, 3=nearly everyday. Higher score indicates greater depression severity. | Baseline, 7 days after third infusion | 
| Clinically significant improvement of depressive symptoms | Number of subjects to show clinically significant improvement in depressive symptoms, defined as a reduction in the PHQ-9 of 5 points or more. | 24 hours after initial infusion | 
| Clinically significant improvement of depressive symptoms | Number of subjects to show clinically significant improvement in depressive symptoms, defined as a reduction in the PHQ-9 of 5 points or more. | 24 hours after third infusion | 
| Clinically significant improvement of depressive symptoms | Number of subjects to show clinically significant improvement in depressive symptoms, defined as a reduction in the PHQ-9 of 5 points or more. | 14 days after third infusion |