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| ID | Type | Description | Link |
|---|---|---|---|
| GY 0002 | Other Identifier | VA Connecticut Healthcare System |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
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| 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). |
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| 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ketamine + Naltrexone | Drug | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | 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. | Day 28 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gihyun Yoon, MD | VA Connecticut Healthcare System West Haven Campus, West Haven, CT | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VA Connecticut Healthcare System West Haven Campus, West Haven, CT | West Haven | Connecticut | 06516-2770 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40795937 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Ketamine + Naltrexone | 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). 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). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 29, 2022 |
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| Ketamine + Placebo | Drug | 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 | Drug | 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). |
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| FG001 | Ketamine + Placebo | 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). 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). |
| FG002 | Placebo (Psychoactive Placebo Midazolam) + Placebo | 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). 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). |
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| NOT COMPLETED |
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Subjects receiving at least one infusion were analyzed
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| ID | Title | Description |
|---|---|---|
| BG000 | Ketamine + Naltrexone | 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). 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). |
| BG001 | Ketamine + Placebo | 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). 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). |
| BG002 | Placebo (Psychoactive Placebo Midazolam) + Placebo | 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). 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). |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Subjects receiving at least one infusion were analyzed | Mean | Standard Deviation | years |
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| Sex: Female, Male | Subjects receiving at least one infusion treatment were analyzed. | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Subjects receiving at least one infusion treatment were analyzed. | Count of Participants | Participants |
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| Montgomery-Åsberg Depression Rating Scale (MADRS) score, mean (SD) | Montgomery-Åsberg Depression Rating Scale (MADRS): The total range: 0 - 60. Higher MADRS scores indicate a worse outcome (i.e., severe depression). | Subjects receiving at least one infusion treatment were analyzed. | Mean | Standard Deviation | units on a scale |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Subjects who completed the outcome measure on Day 21 (after 4th infusion, 240 minutes) | Posted | Count of Participants | Participants | Day 21 (after 4th infusion, 240 minutes) |
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| Primary | 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. | The total number of participants analyzed is inconsistent with the total number of participants reported in the same arm in the Participant Flow---because there is a lot of missing data in the TLFB. | Posted | Count of Participants | Participants | Day 28 |
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During the study period (8 weeks)
Adverse events were collected using the Systematic Assessment for Treatment Emergent Effects (SAFTEE) method.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ketamine + Naltrexone | 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). 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). | 0 | 20 | 0 | 20 | 14 | 20 |
| EG001 | Ketamine + Placebo | 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). 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). | 0 | 19 | 0 | 19 | 11 | 19 |
| EG002 | Placebo (Psychoactive Placebo Midazolam) + Placebo | 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). 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). | 0 | 19 | 0 | 19 | 14 | 19 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blurred or double vision | General disorders | Systematic Assessment |
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| Chest pain, tightness, or discomfort | General disorders | Systematic Assessment |
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| General confusion | General disorders | Systematic Assessment |
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| Confusion as to time, place, person | General disorders | Systematic Assessment |
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| Cough | General disorders | Systematic Assessment |
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| Difficult, troubled breath or shortness of breath | General disorders | Systematic Assessment |
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| Difficult, burning, pain, frequent urge to urinate | General disorders | Systematic Assessment |
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| Difficulty with swallowing | General disorders | Systematic Assessment |
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| General dizziness | General disorders | Systematic Assessment |
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| Dizziness, faintness, lightheadedness upon rising | General disorders | Systematic Assessment |
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| Dream-like state | General disorders | Systematic Assessment |
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| Fast, slow, irregular heartbeat | General disorders | Systematic Assessment |
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| Flushing or redness of skin | General disorders | Systematic Assessment |
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| Irregular, fast, slow, or shallow breathing | General disorders | Systematic Assessment |
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| Itching | General disorders | Systematic Assessment |
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| Loss of appetite | General disorders | Systematic Assessment |
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| Nausea | General disorders | Systematic Assessment |
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| Pain at IV site | General disorders | Systematic Assessment |
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| Pale or blue lips, fingernails, skin | General disorders | Systematic Assessment |
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| Puffiness or swelling of eyelids or eyes | General disorders | Systematic Assessment |
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| Puffiness or swelling around eyes, face, lips, tongue | General disorders | Systematic Assessment |
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| Seeing, hearing, feeling things that are not there | General disorders | Systematic Assessment |
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| Skin rash | General disorders | Systematic Assessment |
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| Sweating | General disorders | Systematic Assessment |
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| Unusually warm skin | General disorders | Systematic Assessment |
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| Unusual excitement, nervousness, restlessness | General disorders | Systematic Assessment |
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| Unusual tiredness or weakness | General disorders | Systematic Assessment |
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| Vomiting | General disorders | Systematic Assessment |
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| Weight loss | General disorders | Systematic Assessment |
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| Headache | General disorders | Systematic Assessment |
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| Drowsiness | General disorders | Systematic Assessment |
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| Anxiety | General disorders | Systematic Assessment |
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| Tiredness | General disorders | Systematic Assessment |
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| Breast Pain | General disorders | Systematic Assessment |
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| Painful menstrual periods | General disorders | Systematic Assessment |
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| Missed menstrual periods | General disorders | Systematic Assessment |
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| Excessive menstrual bleeding | General disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Gihyun Yoon | VA CT Healthcare System, Yale University | (203) 932-5711 | 7421 | gihyun.yoon@yale.edu |
| Oct 29, 2024 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D003865 | Depressive Disorder, Major |
| D000437 | Alcoholism |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
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| ID | Term |
|---|---|
| D007649 | Ketamine |
| D009271 | Naltrexone |
| ID | Term |
|---|---|
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D009270 | Naloxone |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
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| Male |
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| Black |
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| Hispanic or Latino |
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| Other |
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| OG002 | Placebo (Psychoactive Placebo Midazolam) + Placebo | 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). 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). |
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