AlcoholismNCT00588952
Ketamine/Placebo Family History Positive Study
A study of Alcoholism, run by Yale University at 1 site in United States.
Trial summary
The proposed study is the first to explore the contribution of brain glutamate systems, a major target of ethanol in the brain, to the vulnerability to develop alcoholism. This study may lead to an enhanced understanding of the underlying neurobiological mechanism in high-risk individuals that may lead to the… Read more about this study
- Who is it for?
- Ages 21 to 30 yearsHealthy volunteers can take part
- Conditions the study is for
- Alcoholism
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 99 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2001to Jun 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 30 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male and female between the ages of 21 and 30 years
- Medically and neurologically healthy on the basis of history, physical examination, EKG, screening laboratories, absence of current and/or past substance abuse
- For Family History Positive (FHP) Subjects: Biological father and another first or second-degree biological relative with history of alcoholism
Who cannot join
- Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) psychiatric and substance abuse diagnosis by history on psychiatric evaluation that includes a structured diagnostic interview (The Semi-Structured Assessment for the Genetics of alcoholism: SSAGA) and the Wisconsin Scales of Psychosis Proneness
- History of counseling or psychotherapy; except family therapy centered around another family member
- Extended unwillingness to remain alcohol-free for three days prior to testing and for the duration of the testing period
- For women: positive pregnancy test at screening or intention to engage in unprotected sex during the study
- Alcohol naïve
- Previous bad experience with ketamine
- Adoptee and no contact with family members
- For Family History Negative (FHN) Subjects: NO family history of alcoholism in any first or second-degree relatives (subjects must reliably report on three first-degree relatives)
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Connecticut Healthcare System
West Haven, Connecticut, 06516
About this study
Official title: NMDA Dysregulation in Individuals With a Family Vulnerability to Alcoholism
The proposed study is the first to explore the contribution of brain glutamate systems, a major target of ethanol in the brain, to the vulnerability to develop alcoholism. This study may lead to an enhanced understanding of the underlying neurobiological mechanism in high-risk individuals that may lead to the transition from moderate to excessive use of alcohol.
Read the detailed description
Males and females with a paternal family history of alcoholism have a high risk for developing alcoholism. These individuals have been shown to decrease dysphoric responses to alcohol self-administration that may promote the excessive use of alcohol. Ethanol has been shown to be an antagonist at the N-methyl-D-aspartate (NMDA) glutamate receptor. We have recently shown that sober alcoholics have decreased dysphoric response to the NMDA antagonist, ketamine. We propose to test the hypothesis that this characteristic exists as a vulnerability factor in those individuals susceptible to develop alcoholism. Specifically, the objective is to determine whether individuals with a family history positive (FHP) for alcoholism will experience less dysphoric, anxiogenic, and psychotogenic effects to ketamine infusion when compared to family history negative (FHN) control subjects.
Male and female subjects, FHP (biological father and one other first degree relative) between the ages of 21-30, and matched controls (FHN) will complete 2 test days in a randomized balanced order under double-blind conditions. Test days will involve the 60-minute intravenous infusion of placebo and ketamine. Outcome measures include the Biphasic Alcohol Scale and visual analog scales for mood states. Secondary measures include visual analog scales for high, similarity to ethanol, the Sensation Scale (a validated measure of ethanol-like sensations) and aspects of craving for alcohol.
- Conditions
- Alcoholism
- Being tested
- Ketamine and Placebo
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketamine and PlaceboDrug
Also called intravenous
Two test days will involve administration of placebo and Ketamine (0.23 mg/kg, loading dose and infusion rate 0.58 mg/kg/minute) intravenously for 60 minutes
| Study group | Role | What they receive |
|---|---|---|
| Family History Positive | Experimental | Subjects with a positive family history of alcoholism Receives: Drug: Ketamine and Placebo |
| Family History Negative | Experimental | Subjects with a negative family history of alcoholism Receives: Drug: Ketamine and Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation
Self-reporting rating scale to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
Measured: Baseline
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation
Self-reporting rating scale to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
Measured: 15 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation
Self-reporting rating scale to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
Measured: 45 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation
Self-reporting rating scale to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
Measured: 80 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulation
Self-reporting rating scale to measure the stimulation effects (0 not at all stimulated - 70 extremely stimulated) of alcohol effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
Measured: Baseline
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulation
Self-reporting rating scale to measure the stimulation effects (0 not at all stimulated - 70 extremely stimulated) of alcohol effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
Measured: 15 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulation
Self-reporting rating scale to measure the stimulation effects (0 not at all stimulated - 70 extremely stimulated) of alcohol effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
Measured: 45 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulation
Self-reporting rating scale to measure the stimulation effects (0 not at all stimulated - 70 extremely stimulated) of alcohol effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
Measured: 80 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2008 (estimated)
- Study startMar 2001
- Primary completionJun 2015
- Study completionJun 2015
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 AlcoholismStudies 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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 99 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- VA Connecticut Healthcare System, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Sponsor
- Investigators
- Ismene L. Petrakis, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00588952
- Sponsor's protocol ID
- 0103012310
- Other IDs
- VA Alcohol Research Center, P50AA012870
- Status last verified
- Sep 2021
- First submitted
- 27 Dec 2007
- Last updated
- 6 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Yoon G, Pittman B, Limoncelli D, Krystal JH, Petrakis IL. Familial Alcoholism Risk and the Ratio of Stimulant to Sedative Effects of Ketamine. Biol Psychiatry. 2016 May 1;79(9):e69-e70. doi: 10.1016/j.biopsych.2015.09.006. Epub 2015 Sep 25. No abstract available.
PubMed 26475672
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NMDA Dysregulation in Individuals With a Family Vulnerability to Alcoholism
- ClinicalTrials.gov ID
- NCT00588952
- Acronym / sponsor ID
- 0103012310
- Conditions
- Alcoholism
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 99 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- VA Connecticut Healthcare System, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- Mar 2001
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 9 Jan 2008 (estimated)
- Results
- Posted 3 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed study is the first to explore the contribution of brain glutamate systems, a major target of ethanol in the brain, to the vulnerability to develop alcoholism. This study may lead to an enhanced understanding of the underlying neurobiological mechanism in high-risk individuals that may lead to the transition from moderate to excessive use of alcohol.
Detailed description
Males and females with a paternal family history of alcoholism have a high risk for developing alcoholism. These individuals have been shown to decrease dysphoric responses to alcohol self-administration that may promote the excessive use of alcohol. Ethanol has been shown to be an antagonist at the N-methyl-D-aspartate (NMDA) glutamate receptor. We have recently shown that sober alcoholics have decreased dysphoric response to the NMDA antagonist, ketamine. We propose to test the hypothesis that this characteristic exists as a vulnerability factor in those individuals susceptible to develop alcoholism. Specifically, the objective is to determine whether individuals with a family history positive (FHP) for alcoholism will experience less dysphoric, anxiogenic, and psychotogenic effects to ketamine infusion when compared to family history negative (FHN) control subjects.
Male and female subjects, FHP (biological father and one other first degree relative) between the ages of 21-30, and matched controls (FHN) will complete 2 test days in a randomized balanced order under double-blind conditions. Test days will involve the 60-minute intravenous infusion of placebo and ketamine. Outcome measures include the Biphasic Alcohol Scale and visual analog scales for mood states. Secondary measures include visual analog scales for high, similarity to ethanol, the Sensation Scale (a validated measure of ethanol-like sensations) and aspects of craving for alcohol.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Family History Positive | Experimental | Drug: Ketamine and PlaceboSubjects with a positive family history of alcoholism |
| Family History Negative | Experimental | Drug: Ketamine and PlaceboSubjects with a negative family history of alcoholism |
Who may qualify
- Ages
- 21 to 30 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Male and female between the ages of 21 and 30 years
- Medically and neurologically healthy on the basis of history, physical examination, EKG, screening laboratories, absence of current and/or past substance abuse
- For Family History Positive (FHP) Subjects: Biological father and another first or second-degree biological relative with history of alcoholism
Key exclusion criteria (8 listed)
- Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) psychiatric and substance abuse diagnosis by history on psychiatric evaluation that includes a structured diagnostic interview (The Semi-Structured Assessment for the Genetics of alcoholism: SSAGA) and the Wisconsin Scales of Psychosis Proneness
- History of counseling or psychotherapy; except family therapy centered around another family member
- Extended unwillingness to remain alcohol-free for three days prior to testing and for the duration of the testing period
- For women: positive pregnancy test at screening or intention to engage in unprotected sex during the study
- Alcohol naïve
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 |
|---|---|---|
| Ketamine and PlaceboAlso: intravenousTwo test days will involve administration of placebo and Ketamine (0.23 mg/kg, loading dose and infusion rate 0.58 mg/kg/minute) intravenously for 60 minutes | Drug | Family History Negative, Family History Positive |
Primary outcome
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation
Time frame: Baseline
Self-reporting rating scale to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation
Time frame: 15 minutes
Self-reporting rating scale to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation
Time frame: 45 minutes
Self-reporting rating scale to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation
Time frame: 80 minutes
Self-reporting rating scale to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulation
Time frame: Baseline
Self-reporting rating scale to measure the stimulation effects (0 not at all stimulated - 70 extremely stimulated) of alcohol effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulation
Time frame: 15 minutes
Self-reporting rating scale to measure the stimulation effects (0 not at all stimulated - 70 extremely stimulated) of alcohol effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulation
Time frame: 45 minutes
Self-reporting rating scale to measure the stimulation effects (0 not at all stimulated - 70 extremely stimulated) of alcohol effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulation
Time frame: 80 minutes
Self-reporting rating scale to measure the stimulation effects (0 not at all stimulated - 70 extremely stimulated) of alcohol effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26475672Yoon G, Pittman B, Limoncelli D, Krystal JH, Petrakis IL. Familial Alcoholism Risk and the Ratio of Stimulant to Sedative Effects of Ketamine. Biol Psychiatry. 2016 May 1;79(9):e69-e70. doi: 10.1016/j.biopsych.2015.09.006. Epub 2015 Sep 25. No abstract available.
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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 L. Petrakis, MD 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 study of Alcoholism, 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 3 inclusion and 8 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 6 Oct 2021. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation (time frame: Baseline). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00588952, which also lists 1 linked publication.
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 6 Oct 2021.