Ketamine for the Rapid Treatment of Major Depressive Disorder and Alcohol Use Disorder

Major Depressive Disorder Clinical Trial

Official title:

Ketamine for The Rapid Treatment of Major Depression and Alcohol Use Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02461927
• Other study ID #: MHBB-009-16F
• Secondary ID: GY 0002
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 1, 2015
• Est. completion date: October 30, 2023

Study information

• Verified date: October 2023
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: October 30, 2023
• Est. primary completion date: October 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Alcohol Drinking
• Alcohol Use Disorder
• Alcoholism
• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• Ketamine + Naltrexone
Subjects in this arm will receive (1) intravenous ketamine (0.5 mg/kg) once a week for 4 weeks (a total of 4 infusions) and (2) intramuscular naltrexone (380 mg) once a month (a total of 2 injections).
• Ketamine + Placebo
Subjects in this arm will receive (1) intravenous ketamine (0.5 mg/kg) once a week for 4 weeks (a total of 4 infusions) and (2) intramuscular placebo once a month (a total of 2 injections).
• Placebo (psychoactive placebo midazolam) + Placebo
Subjects in this arm will receive (1) intravenous psychoactive placebo midazolam (0.045 mg/kg) once a week for 4 weeks (a total of 4 infusions) and (2) intramuscular placebo once a month (a total of 2 injections).

Locations

Country	Name	City	State
United States	VA Connecticut Healthcare System West Haven Campus, West Haven, CT	West Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Montgomery-Asberg Depression Rating Scale (MADRS)	Severity of depression	Day 21 (after 4th infusion, 240 minutes)
Primary	Time Line Follow Back (TLFB)	Rate of complete abstinence from alcohol	Day 28