Clinical trial NCT02461927: Ketamine for the Rapid Treatment of Major Depressive Disorder and Alcohol Use Disorder
Official title: Ketamine for The Rapid Treatment of Major Depression and Alcohol Use Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Major Depressive Disorder
Alcohol Use Disorder
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2015-06-03
Enrollment: 65
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators will compare 3 treatment groups (ketamine plus naltrexone vs. ketamine alone vs. placebo) for treating major depressive disorder (MDD) and alcohol use disorder (AUD) in an 8-week randomized, double-blind, placebo-controlled, between-subjects trial. First, prior to the double-blind trial, the investigators will conduct an open-label trial that will include 5 patients with comorbid MDD and AUD to test safety and efficacy of repeated ketamine treatment (0.5 mg/kg; once a week for 4 weeks; a total of 4 ketamine infusions) with a follow-up of 4 weeks. Second, after reviewing the safety and efficacy of repeated ketamine treatment from the open-label trial, the investigators will conduct an 8-week, randomized, double-blind, placebo-controlled trial that will include 60 patients with comorbid MDD and AUD to test safety and efficacy of repeated ketamine treatment (0.5 mg/kg; once a week for 4 weeks; a total of 4 ketamine infusions) plus naltrexone with a follow-up of 4 weeks. The 4-month follow-up session will also occur.


Eligibility criteria: Inclusion Criteria:

* Male or female veterans and civilians, 21-65 years old
* Current major depressive disorder without psychotic features by DSM-5 (antidepressant regimens can be allowed and changed during the trial)
* Montgomery-Asberg Depression Rating Scale (MADRS) 20 or higher
* A minimum of 4 of 11 current alcohol use disorder symptoms by DSM-5
* Heavy drinking at least 4 times in the past month ('heavy drinking' defined as 5 standard drinks per day for men and 4 standard drinks per day for women
* Able to provide written informed consent

Exclusion Criteria:

* Current substance use disorder by DSM-5 in the past 3 months (except alcohol, tobacco, or cannabis)
* Current or past history of psychotic features or psychotic disorder
* Current dementia
* Current uncontrolled hypertension (systolic BP \> 170 mm Hg or diastolic BP \> 100 mm Hg)
* Unstable medical condition or allergy to ketamine, midazolam, naltrexone, or lorazepam---clinically determined by a physician
* Imminent suicidal or homicidal risk
* Pregnant or nursing women, positive pregnancy test, or inadequate birth control methods in women of childbearing potential
* Positive opioid or illicit drug screen test (except marijuana)
* Opioid use within 10 days prior to study medication (injectable naltrexone) or risks for opioid use during the study
* Liver enzymes that are three times higher than the upper limit of normal
* Current use of benzodiazepine
* Acute narrow-angle glaucoma
* Severe sleep apnea---clinically determined by a physician

Primary outcomes:
measure: Number of Participants With 50% or Greater Improvement in MADRS Scores From Baseline
timeFrame: Day 21 (after 4th infusion, 240 minutes)
measure: Rate of Complete Abstinence From Alcohol
timeFrame: Day 28
Secondary outcomes:
Other outcomes:
Locations:
city: West Haven
country: United States
facility: VA Connecticut Healthcare System West Haven Campus, West Haven, CT
state: Connecticut
Study officials:
affiliation: VA Connecticut Healthcare System West Haven Campus, West Haven, CT
name: Gihyun Yoon, MD
role: PRINCIPAL_INVESTIGATOR
References: