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

Primary Purpose

Major Depressive Disorder, Alcohol Use Disorder

Status

Active

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Ketamine + Naltrexone

Ketamine + Placebo

Placebo (psychoactive placebo midazolam) + Placebo

About this trial

This is an interventional treatment trial for Major Depressive Disorder

Eligibility Criteria

21 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Sites / Locations

VA Connecticut Healthcare System West Haven Campus, West Haven, CT

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Ketamine + Naltrexone

Ketamine + Placebo

Placebo (psychoactive placebo midazolam) + Placebo

Arm Description

Subjects in this arm will receive (1) intravenous ketamine treatment once a week for 4 weeks (a total of 4 infusions) with a follow-up of 4 weeks and (2) intramuscular naltrexone once a month (a total of 2 injections).

Subjects in this arm will receive (1) intravenous ketamine treatment once a week for 4 weeks (a total of 4 infusions) with a follow-up of 4 weeks and (2) intramuscular placebo once a month (a total of 2 injections).

Subjects in this arm will receive (1) intravenous placebo treatment (psychoactive placebo midazolam) once a week for 4 weeks (a total of 4 infusions) with a follow-up of 4 weeks and (2) intramuscular placebo once a month (a total of 2 injections).

Outcomes

Primary Outcome Measures

Montgomery-Asberg Depression Rating Scale (MADRS)

Severity of depression

Time Line Follow Back (TLFB)

Rate of complete abstinence from alcohol

Secondary Outcome Measures

Full Information

NCT ID

NCT02461927

First Posted

June 1, 2015

Last Updated

August 2, 2023

Sponsor

VA Office of Research and Development

1. Study Identification

Unique Protocol Identification Number

NCT02461927

Brief Title

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

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

January 1, 2015 (Actual)

Primary Completion Date

October 31, 2023 (Anticipated)

Study Completion Date

October 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

VA Office of Research and Development

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Major Depressive Disorder, Alcohol Use Disorder

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

65 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ketamine + Naltrexone

Arm Type

Experimental

Arm Description

Arm Title

Ketamine + Placebo

Arm Type

Experimental

Arm Description

Arm Title

Placebo (psychoactive placebo midazolam) + Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Ketamine + Naltrexone

Intervention Description

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).

Intervention Type

Drug

Intervention Name(s)

Ketamine + Placebo

Intervention Description

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).

Intervention Type

Drug

Intervention Name(s)

Placebo (psychoactive placebo midazolam) + Placebo

Intervention Description

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).

Primary Outcome Measure Information:

Title

Montgomery-Asberg Depression Rating Scale (MADRS)

Description

Severity of depression

Time Frame

Day 21 (after 4th infusion, 240 minutes)

Title

Time Line Follow Back (TLFB)

Description

Rate of complete abstinence from alcohol

Time Frame

Day 28

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gihyun Yoon, MD

Organizational Affiliation

VA Connecticut Healthcare System West Haven Campus, West Haven, CT

Official's Role

Principal Investigator

Facility Information:

Facility Name

VA Connecticut Healthcare System West Haven Campus, West Haven, CT

City

West Haven

State/Province

Connecticut

ZIP/Postal Code

06516-2770

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

Learn more about this trial

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

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