Major Depressive DisorderPhase 1/2NCT02461927
Ketamine for the Rapid Treatment of Major Depressive Disorder and Alcohol Use Disorder
A Phase 1/2 study testing Ketamine + Naltrexone in people with Major Depressive Disorder and Alcohol Use Disorder, run by VA Office of Research and Development at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Major Depressive Disorder, Alcohol Use Disorder
- What is being tested?
- Ketamine + Naltrexone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2015to 30 Oct 2023
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Connecticut Healthcare System West Haven Campus, West Haven, CT
West Haven, Connecticut, 06516-2770
About this study
Official title: Ketamine for The Rapid Treatment of Major Depression and Alcohol Use Disorder
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.
- Conditions
- Major Depressive Disorder, Alcohol Use Disorder
- Being tested
- Ketamine + Naltrexone, Ketamine + Placebo, Placebo (psychoactive placebo midazolam) + Placebo
- Medical subject headings
- Depressive Disorder, Major, Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketamine + NaltrexoneDrug
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 + PlaceboDrug
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) + PlaceboDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| Ketamine + Naltrexone | Experimental | 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). Receives: Drug: Ketamine + Naltrexone |
| Ketamine + Placebo | Experimental | 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). Receives: Drug: Ketamine + Placebo |
| Placebo (psychoactive placebo midazolam) + Placebo | Placebo comparator | 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). Receives: Drug: Placebo (psychoactive placebo midazolam) + Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With 50% or Greater Improvement in MADRS Scores From Baseline
Our primary analysis (severity of depression) was to compare the proportions of subjects with clinical response in symptoms of major depressive disorder (response defined as a 50% or greater improvement from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) scores) at the end-of-treatment time point (Day 21, after 4th infusion, T+240 minutes).
Measured: Day 21 (after 4th infusion, 240 minutes)
Rate of Complete Abstinence From Alcohol
Alcohol consumption was measured using the Time Line Follow Back (TLFB) method. The rates of complete abstinence from alcohol across visits 3 (day 0) through visit 7 (day 28) were compared among the three study groups.
Measured: Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2015 (estimated)
- Study start1 Jan 2015
- Primary completion30 Oct 2023
- Study completion30 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Gihyun Yoon, MD, Principal investigator, VA Connecticut Healthcare System West Haven Campus, West Haven, CT
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02461927
- Sponsor's protocol ID
- MHBB-009-16F
- Other IDs
- GY 0002
- Status last verified
- Apr 2025
- First submitted
- 1 Jun 2015
- Last updated
- 10 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Yoon G, Pittman B, Ralevski E, Petrakis IL, Krystal JH. Antidepressant efficacy of ketamine plus naltrexone for major depression comorbid with alcohol use disorder: a randomized controlled trial. Int J Neuropsychopharmacol. 2025 Aug 1;28(8):pyaf056. doi: 10.1093/ijnp/pyaf056.
PubMed 40795937