DepressionPhase 1KetamineDepNCT01551329
Ketamine for Depression and Alcohol Dependence
A Phase 1 study testing Ketalar (ketamine) in people with Depression and Alcohol Dependence, run by Yale University at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the efficacy of ketamine in reducing depressive symptoms in subjects with a comorbid major depressive episode and alcohol dependence. The investigators hypothesize the following for the present study: A single dose of ketamine will induce a rapid, robust and sustained reduction… Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Depression, Alcohol Dependence
- What is being tested?
- Ketalar (ketamine)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2012to Nov 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 (post-menopausal, surgically sterile or negative pregnancy test at screening and agreement to utilize a medically-approved birth control method including complete abstinence during the testing period) between the age of 21 and 65 years old.
- Able to provide written informed consent according to the WHVA and Yale HIC guidelines.
- Medically and neurologically healthy on the basis of medical history, physical examination, EKG, and screening laboratories (CBC w/ differential, basic metabolic profile including BUN/creatinine, TSH, fT4, AST, ALT, GGT, total protein, albumin, vitamin B12, folate, VDRL, HIV, hepatitis B and C, urinalysis, HCG, and urine toxicology screen). Predefined exclusion criteria are identified, e.g. LFTs > 3x upper limit of normal. Individuals with stable medical problems that do not have direct CNS effects, e.g. hypertension and diabetes mellitus, or interfere with medications administered, e.g. oral hypoglycemics, may be included if their medications have not been adjusted in the month prior to study enrollment.
- Current DSM-IV-TR major depressive episode (MDE) by structured clinical interview (SCID) and a MADRS score ¬>20.
- Current DSM-IV-TR alcohol dependence with one heavy drinking day (> 4 standard drinks/session for men and > 3 standard drinks/session for women) in the last 3 weeks.
- Abstinent from drinking for > 5 days prior to receiving ketamine.
- No current psychotropic medications (excluding benzodiazepines during alcohol detoxification if needed) in last 2 weeks (4 weeks for fluoxetine).
- Individuals who have completed a detoxification program and who are at least 5 days past their last drink.
Who cannot join
- Unstable medical condition or medical problem with known CNS effects, e.g. uncontrolled hypertension (SBP≥170 and/or DBP≥100) or confirmed history of alcohol-withdrawal seizures.
- Active suicidal ideation, intent or plan.
- Active DSM-IV-TR substance use disorder in past three months (other than an alcohol or nicotine use disorder).
- Prior diagnosis of a DSM-IV-TR psychotic spectrum disorder, e.g. schizophrenia, schizoaffective disorder, bipolar I d/o with psychotic features, MDD with psychotic features.
Trial locations and contacts
1 site in 1 country.
United States1 site
VA CT Healthcare Systems
West Haven, Connecticut, 06516
About this study
Official title: A Randomized Controlled Trial of the N-methyl-D-aspartate (NMDA) Receptor Antagonist Ketamine in Comorbid Depression and Alcohol Dependence.
The purpose of this study is to evaluate the efficacy of ketamine in reducing depressive symptoms in subjects with a comorbid major depressive episode and alcohol dependence. The investigators hypothesize the following for the present study:
A single dose of ketamine will induce a rapid, robust and sustained reduction in depressive symptoms in subjects with a comorbid major depressive episode and alcohol dependence relative to placebo as defined by change in Hamilton Depression Rating Scale total scores at 72 hours post infusion.
A single dose of ketamine can be delivered safely, with minimal adverse events or complications, in subjects with a comorbid major depressive episode and alcohol dependence.
Read the detailed description
Major depression and alcohol dependence are both within the ten disorders for highest worldwide disease burden as identified by the World Health Organization (WHO), and these disorders frequently co-occur, especially in high-service utilizing patients with severe and persistent mental illness. Currently available treatments are inadequate for both chronic conditions alone, and the inadequacy is even clearer in people meeting criteria for both disorders. Ketamine was first reported as a rapidly-acting antidepressant in 2000 via research occurring at Yale, and, since that time, in several small randomized controlled trials, a single subanesthetic dose of intravenous ketamine has demonstrated efficacy in improving mood in unipolar and bipolar depression within only hours after administration. These effects can last at least a week. Interestingly, ketamine has been demonstrated to produce a more robust effect in treatment-refractory unipolar depressed subjects with a family history of alcoholism relative to similarly difficult-to-treat subjects without a family history of alcohol problems. In addition, recently-detoxified alcoholics have been safely administered subanesthetic doses of ketamine, and, during these infusions, alcoholics (and even those with only a family history of alcoholism) displayed a differential response to ketamine, e.g. blunted psychotic-like and cognitive effects, relative to healthy controls. Therefore, ketamine may reduce depressive symptoms and alcohol consumption compared to placebo in patients with comorbid major depression and current alcohol dependence. Positive results will mark a major advance in the clinical care of those being treated for both conditions and will open the door for further scientific investigations into the clinical neuroscience of these highly comorbid and prevalent conditions.
This is a two phase, double-blind, randomized, placebo-controlled, cross-over, proof-of-concept study designed to determine the effects of a single dose of ketamine, administered IV, on mood and alcohol consumption, in psychotropic medication-free patients meeting DSM-IV-TR criteria for a major depressive episode (MDE) and current alcohol dependence. Participants will be assigned randomly to receive either intravenous ketamine (0.5mg/kg) or saline solution 2 weeks apart in a cross over design. The ketamine dose was based on previous studies in patients with depression and bipolar disorder. A team member experienced with ketamine infusions will administer the study medication over a 40-minute infusion in a blinded fashion at the Biological Studies Unit at the WHVA.
20 depressed alcohol dependent subjects between the ages of 21-65 will be recruited for this study through advertising and the West Haven VA clinics. Subjects will complete an informed consent process and will be thoroughly screened for inclusion and exclusion criteria as described below. Individuals will be given a post consent test to evaluate their understanding of the procedure. For subjects who provide incorrect answers to any of the test items, the research staff will review the correct answers with the subject and show the subject where the correct answers are found in the consent form. Those who get more than 60% of the questions wrong and are still unable to understand the procedure after reviewing it with the research staff will be excluded from the study. They will be referred to appropriate resources for outpatient treatment of their depression and alcoholism. Before start of the study all patients will be free of any psychotropic medications.
- Conditions
- Depression, Alcohol Dependence
- Being tested
- Ketalar (ketamine)
- Keywords
- depression, alcohol, comorbidity, ketamine, glutamate, NMDA
- Medical subject headings
- Depression, Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketalar (ketamine)Drug
Intravenous Ketamine 0.5mg/kg
| Study group | Role | What they receive |
|---|---|---|
| Drug: Ketamine | Experimental | Not described Receives: Drug: Ketalar (ketamine) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Depression
Measured using the Hamilton Depression Rating Scale
Measured: 29 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2012 (estimated)
- Study startMar 2012
- Primary completionNov 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- VA Connecticut Healthcare System
- Responsible party
- Principal investigator, Ismene Petrakis, Yale University
- Investigators
- Ismene Petrakis, M.D., Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01551329
- Sponsor's protocol ID
- 1111009339
- Acronym
- KetamineDep
- Status last verified
- Mar 2020
- First submitted
- 7 Mar 2012
- Last updated
- 9 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial of the N-methyl-D-aspartate (NMDA) Receptor Antagonist Ketamine in Comorbid Depression and Alcohol Dependence.
- ClinicalTrials.gov ID
- NCT01551329
- Acronym / sponsor ID
- KetamineDep / 1111009339
- Conditions
- Depression, Alcohol Dependence
- Keywords
- depression, alcohol, comorbidity, ketamine, glutamate, NMDA
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- VA Connecticut Healthcare System
- Study start
- Mar 2012
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 12 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy of ketamine in reducing depressive symptoms in subjects with a comorbid major depressive episode and alcohol dependence. The investigators hypothesize the following for the present study:
A single dose of ketamine will induce a rapid, robust and sustained reduction in depressive symptoms in subjects with a comorbid major depressive episode and alcohol dependence relative to placebo as defined by change in Hamilton Depression Rating Scale total scores at 72 hours post infusion.
A single dose of ketamine can be delivered safely, with minimal adverse events or complications, in subjects with a comorbid major depressive episode and alcohol dependence.
Detailed description
Major depression and alcohol dependence are both within the ten disorders for highest worldwide disease burden as identified by the World Health Organization (WHO), and these disorders frequently co-occur, especially in high-service utilizing patients with severe and persistent mental illness. Currently available treatments are inadequate for both chronic conditions alone, and the inadequacy is even clearer in people meeting criteria for both disorders. Ketamine was first reported as a rapidly-acting antidepressant in 2000 via research occurring at Yale, and, since that time, in several small randomized controlled trials, a single subanesthetic dose of intravenous ketamine has demonstrated efficacy in improving mood in unipolar and bipolar depression within only hours after administration. These effects can last at least a week. Interestingly, ketamine has been demonstrated to produce a more robust effect in treatment-refractory unipolar depressed subjects with a family history of alcoholism relative to similarly difficult-to-treat subjects without a family history of alcohol problems. In addition, recently-detoxified alcoholics have been safely administered subanesthetic doses of ketamine, and, during these infusions, alcoholics (and even those with only a family history of alcoholism) displayed a differential response to ketamine, e.g. blunted psychotic-like and cognitive effects, relative to healthy controls. Therefore, ketamine may reduce depressive symptoms and alcohol consumption compared to placebo in patients with comorbid major depression and current alcohol dependence. Positive results will mark a major advance in the clinical care of those being treated for both conditions and will open the door for further scientific investigations into the clinical neuroscience of these highly comorbid and prevalent conditions.
This is a two phase, double-blind, randomized, placebo-controlled, cross-over, proof-of-concept study designed to determine the effects of a single dose of ketamine, administered IV, on mood and alcohol consumption, in psychotropic medication-free patients meeting DSM-IV-TR criteria for a major depressive episode (MDE) and current alcohol dependence. Participants will be assigned randomly to receive either intravenous ketamine (0.5mg/kg) or saline solution 2 weeks apart in a cross over design. The ketamine dose was based on previous studies in patients with depression and bipolar disorder. A team member experienced with ketamine infusions will administer the study medication over a 40-minute infusion in a blinded fashion at the Biological Studies Unit at the WHVA.
20 depressed alcohol dependent subjects between the ages of 21-65 will be recruited for this study through advertising and the West Haven VA clinics. Subjects will complete an informed consent process and will be thoroughly screened for inclusion and exclusion criteria as described below. Individuals will be given a post consent test to evaluate their understanding of the procedure. For subjects who provide incorrect answers to any of the test items, the research staff will review the correct answers with the subject and show the subject where the correct answers are found in the consent form. Those who get more than 60% of the questions wrong and are still unable to understand the procedure after reviewing it with the research staff will be excluded from the study. They will be referred to appropriate resources for outpatient treatment of their depression and alcoholism. Before start of the study all patients will be free of any psychotropic medications.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Drug: Ketamine | Experimental | Drug: Ketalar (ketamine) |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female (post-menopausal, surgically sterile or negative pregnancy test at screening and agreement to utilize a medically-approved birth control method including complete abstinence during the testing period) between the age of 21 and 65 years old.
- Able to provide written informed consent according to the WHVA and Yale HIC guidelines.
- Medically and neurologically healthy on the basis of medical history, physical examination, EKG, and screening laboratories (CBC w/ differential, basic metabolic profile including BUN/creatinine, TSH, fT4, AST, ALT, GGT, total protein, albumin, vitamin B12, folate, VDRL, HIV, hepatitis B and C, urinalysis, HCG, and urine toxicology screen). Predefined exclusion criteria are identified, e.g. LFTs > 3x upper limit of normal. Individuals with stable medical problems that do not have direct CNS effects, e.g. hypertension and diabetes mellitus, or interfere with medications administered, e.g. oral hypoglycemics, may be included if their medications have not been adjusted in the month prior to study enrollment.
- Current DSM-IV-TR major depressive episode (MDE) by structured clinical interview (SCID) and a MADRS score ¬>20.
- Current DSM-IV-TR alcohol dependence with one heavy drinking day (> 4 standard drinks/session for men and > 3 standard drinks/session for women) in the last 3 weeks.
Key exclusion criteria (4 listed)
- Unstable medical condition or medical problem with known CNS effects, e.g. uncontrolled hypertension (SBP≥170 and/or DBP≥100) or confirmed history of alcohol-withdrawal seizures.
- Active suicidal ideation, intent or plan.
- Active DSM-IV-TR substance use disorder in past three months (other than an alcohol or nicotine use disorder).
- Prior diagnosis of a DSM-IV-TR psychotic spectrum disorder, e.g. schizophrenia, schizoaffective disorder, bipolar I d/o with psychotic features, MDD with psychotic features.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketalar (ketamine)Intravenous Ketamine 0.5mg/kg | Drug | Drug: Ketamine |
Primary outcome
Depression
Time frame: 29 Days
Measured using the Hamilton Depression Rating Scale
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ismene Petrakis, M.D. principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ketalar (ketamine) in people with Depression and Alcohol Dependence, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Depression (time frame: 29 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2020.