AlcoholismNCT00611767
GABA Mechanisms Underlying the Vulnerability to Alcohol Dependence
A study testing Thiopental in people with Alcoholism, run by Yale University at 1 site in United States.
Trial summary
This Project will explore the hypothesis that individuals with a family history positive for alcohol dependence (without any current Axis I disorder, except nicotine dependence), experience an alteration in the reward "valence" (balance of positive and negative effects) of the GABAA receptor agonist barbiturate… Read more about this study
- Who is it for?
- Ages 21 to 30 yearsHealthy volunteers can take part
- Conditions the study is for
- Alcoholism
- What is being tested?
- Thiopental
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 73 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2005to Apr 2012
- 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, Electrocardiogram (EKG), screening laboratories
- absence of any evidence of substance abuse (with the exception of nicotine dependence) on the basis of history and drug and ethanol-free at the time of testing based on urine toxicology and breath alcohol levels at screening and on each test day.
Who cannot join
- Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) Axis I psychiatric and substance abuse or dependence diagnosis by history on psychiatric evaluation that includes a structured diagnostic interview (SCID)
- unwillingness to remain alcohol-free for three days prior to each test day;
- for women, positive pregnancy test at screening or intention to engage in unprotected sex during the study and
- alcohol naive. For Family History Positive Subjects: 1) Biological father and another first or second-degree biological relative with history of alcoholism by Family History Assessment Module (FHAM) developed by The Collaborative Study on the Genetics of Alcoholism (COGA).
- For Family History Negative 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: Gamma-Aminobutyric Acid (GABA) Mechanisms Underlying the Vulnerability to Alcohol Dependence
This Project will explore the hypothesis that individuals with a family history positive for alcohol dependence (without any current Axis I disorder, except nicotine dependence), experience an alteration in the reward "valence" (balance of positive and negative effects) of the GABAA receptor agonist barbiturate (thiopental) compared to family history negative age-matched subjects. Further, variation in genes involved in brain GABA function may influence the risk for alcoholism by altering a component of the discriminative stimulus effects of ethanol.
Read the detailed description
This project will explore the hypothesis that individuals with a family history positive for alcohol dependence (FHP) (without any current DSM-IV Axis I disorder, except nicotine dependence), experience an alteration in the reward "valence" (balance of positive and negative effects) of the GABA-A receptor agonist barbiturate (thiopental) compared to family history negative (FHN) age-matched subjects. Further, the effect of variations in genes important in regulating brain GABA function may alter a component of the discriminative stimulus effects of ethanol. FHP individuals are defined as individuals with at least one first-degree relative and another first- or second-degree relatives. Preliminary results suggest that FHP individuals showed an attenuated response to thiopental as measured by the descending limb of the BAES during thiopental infusion relative to the FHN group. Further, preliminary results suggest that variation in genes involved in brain GABA function, glutamate decarboxylase-65 (GAD65), may influence the risk for alcoholism by altering a component of the discriminative stimulus effects of ethanol.
We plan to recruit 2 groups of healthy subjects between the ages of 21-30, one with a family history of alcoholism (family history positive=FHP) and a sex-matched control group without a family history of alcoholism (family history negative=FHN), to undergo two test days scheduled 3 days apart, in a randomized double-blind fashion. Test days will involve a 60-minute intravenous infusion of each of 2 conditions: saline or thiopental, in a randomized order under double-blind conditions. Behavioral ratings include the Biphasic Alcohol Effects Scale (BAES) and Visual Analog Scales (VAS). Exploratory measures include event-related potential recordings (ERP) and measures of eye-to-hand coordination. Blood will be collected for Deoxyribonucleic acid (DNA) extraction and genotyping.
- Conditions
- Alcoholism
- Being tested
- Thiopental, Placebo
- Keywords
- Thiopental, Alcohol, Family History, Vulnerability, GABA
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThiopentalDrug
A 2-day test design involving 2 conditions: saline (Placebo) or Thiopental 1.5mg/kg (loading) with a subsequent infusion rate of 40 mcg/kg/minute (60 minute infusion).
PlaceboDrug
A 2-day test design involving 2 conditions: saline (Placebo) or Thiopental 1.5mg/kg (loading) with a subsequent infusion rate of 40 mcg/kg/minute (60 minute infusion).
| Study group | Role | What they receive |
|---|---|---|
| Family History Negative for Alcoholism | Active comparator | Family History Negative for Alcoholism subjects will receive 2 interventions Receives: Drug: Thiopental |
| Family History Positive for Alcoholism | Placebo comparator | Family History Positive for Alcoholism subjects will receive 2 interventions Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Visual Analog Scales of Similarity to Alcohol - Baseline
Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Measured: Baseline
Visual Analog Scales of Similarity to Alcohol - 15 Minutes
Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Measured: 15 minutes
Visual Analog Scales of Similarity to Alcohol - 45 Minutes
Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Measured: 45 minutes
Visual Analog Scales of Similarity to Alcohol - 80 Minutes
Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Measured: 80 minutes
Visual Analog Scales of Similarity to Alcohol - 110 Minutes
Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Measured: 110 minutes
Visual Analog Scales of Similarity to Alcohol - 170 Minutes
Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Measured: 170 minutes
Visual Analog Scales of Similarity to Alcohol - 230 Minutes
Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Measured: 230 minutes
Secondary outcomes (71)
Number of Drinks Felt Consumed at Baseline
The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.
Measured: Baseline
Number of Drinks Felt Consumed - 15 Minutes
The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.
Measured: 15 minutes
Number of Drinks Felt Consumed - 45 Minutes
The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.
Measured: 45 minutes
Number of Drinks Felt Consumed - 80 Minutes
The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.
Measured: 80 minutes
Number of Drinks Felt Consumed - 110 Minutes
The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.
Measured: 110 minutes
Number of Drinks Felt Consumed - 170 Minutes
The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.
Measured: 170 minutes
Number of Drinks Felt Consumed - 230 Minutes
The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.
Measured: 230 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - Baseline
Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)
Measured: Baseline
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 15 Minutes
Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)
Measured: 15 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 45 Minutes
Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)
Measured: 45 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 80 Minutes
Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)
Measured: 80 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant- 110 Minutes
Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)
Measured: 110 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 170 Minutes
Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)
Measured: 170 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 230 Minutes
Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)
Measured: 230 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative Baseline
Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Measured: Baseline
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 15 Minutes
Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Measured: 15 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 45 Minutes
Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Measured: 45 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 80 Minutes
Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Measured: 80 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 110 Minutes
Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Measured: 110 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 170 Minutes
Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Measured: 170 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 230 Minutes
Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Measured: 230 minutes
Visual Analog Scales (VAS) - High - Baseline
visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Measured: Baseline
Visual Analog Scales (VAS) - High - 15 Minutes
visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Measured: 15 minutes
Visual Analog Scales (VAS) - High - 45 Minutes
visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Measured: 45 minutes
Visual Analog Scales (VAS) - High - 80 Minutes
visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Measured: 80 minutes
Visual Analog Scales (VAS) - High - 110 Minutes
visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Measured: 110 minutes
Visual Analog Scales (VAS) - High - 170 Minutes
visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Measured: 170 minutes
Visual Analog Scales (VAS) - High - 230 Minutes
visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Measured: 230 minutes
Visual Analog Scales (VAS) - Buzzed - Baseline
visual analog scale (VAS): self-report scale used to measure buzzed (0 not at all buzzed - 7 extremely buzzed)
Measured: Baseline
Visual Analog Scales (VAS) - Buzzed - 15 Minutes
visual analog scale (VAS): self-report scale used to measure buzzed (0 not at all buzzed - 7 extremely buzzed)
Measured: 15 minutes
Visual Analog Scales (VAS) - Buzzed - 45 Minutes
visual analog scale (VAS): self-report scale used to measure buzzed (0 not at all buzzed - 7 extremely buzzed)
Measured: 45 minutes
Visual Analog Scales (VAS) - Buzzed - 80 Minutes
visual analog scale (VAS): self-report scale used to measure buzzed (0 not at all buzzed - 7 extremely buzzed)
.
Measured: 80 minutes
Visual Analog Scales (VAS) - Buzzed - 110 Minutes
visual analog scale (VAS): self-report scale used to measure buzzed (0 not at all buzzed - 7 extremely buzzed)
Measured: 110 minutes
Visual Analog Scales (VAS) - Buzzed - 170 Minutes
visual analog scale (VAS): self-report scale used to measure buzzed (0 not at all buzzed - 7 extremely buzzed)
Measured: 170 minutes
Visual Analog Scales (VAS) - Buzzed - 230 Minutes
visual analog scale (VAS): self-report scale used to measure buzzed (0 not at all buzzed - 7 extremely buzzed)
Measured: 230 minutes
Visual Analog Scales (VAS) - Drowsy - Baseline
visual analog scale (VAS): self-report scale used to measure drowsy (0 not at all drowsy - 7 extremely drowsy)
Measured: Baseline
Visual Analog Scales (VAS) - Drowsy - 15 Minutes
visual analog scale (VAS): self-report scale used to measure drowsy (0 not at all drowsy - 7 extremely drowsy)
Measured: 15 minutes
Visual Analog Scales (VAS) - Drowsy - 45 Minutes
visual analog scale (VAS): self-report scale used to measure drowsy (0 not at all drowsy - 7 extremely drowsy)
.
Measured: 45 minutes
Visual Analog Scales (VAS) - Drowsy - 80 Minutes
visual analog scale (VAS): self-report scale used to measure drowsy (0 not at all drowsy - 7 extremely drowsy)
Measured: 80 minutes
Visual Analog Scales (VAS) - Drowsy - 110 Minutes
visual analog scale (VAS): self-report scale used to measure drowsy (0 not at all drowsy - 7 extremely drowsy)
Measured: 110 minutes
Visual Analog Scales (VAS) - Drowsy - 170 Minutes
visual analog scale (VAS): self-report scale used to measure drowsy (0 not at all drowsy - 7 extremely drowsy)
Measured: 170 minutes
Visual Analog Scales (VAS) - Drowsy - 230 Minutes
visual analog scale (VAS): self-report scale used to measure drowsy (0 not at all drowsy - 7 extremely drowsy)
Measured: 230 minutes
Visual Analog Scales (VAS) - Depressed - Baseline
visual analog scale (VAS): self-report scale used to measure depressed (0 not at all depressed - 7 extremely depressed)
Measured: Baseline
Visual Analog Scales (VAS) - Depressed - 15 Minutes
visual analog scale (VAS): self-report scale used to measure depressed (0 not at all depressed - 7 extremely depressed)
Measured: 15 minutes
Visual Analog Scales (VAS) - Depressed - 45 Minutes
visual analog scale (VAS): self-report scale used to measure depressed (0 not at all depressed - 7 extremely depressed)
Measured: 45 minutes
Visual Analog Scales (VAS) - Depressed - 80 Minutes
visual analog scale (VAS): self-report scale used to measure depressed (0 not at all depressed - 7 extremely depressed)
Measured: 80 minutes
Visual Analog Scales (VAS) - Depressed - 110 Minutes
visual analog scale (VAS): self-report scale used to measure depressed (0 not at all depressed - 7 extremely depressed)
Measured: 110 minutes
Visual Analog Scales (VAS) - Depressed - 170 Minutes
visual analog scale (VAS): self-report scale used to measure depressed (0 not at all depressed - 7 extremely depressed)
Measured: 170 minutes
Visual Analog Scales (VAS) - Depressed - 230 Minutes
visual analog scale (VAS): self-report scale used to measure depressed (0 not at all depressed - 7 extremely depressed)
Measured: 230 minutes
Visual Analog Scales (VAS) - Anxious - Baseline
visual analog scale (VAS): self-report scale used to measure anxiety (0 not at all anxious - 7 extremely anxious)
Measured: Baseline
Visual Analog Scales (VAS) - Anxious - 15 Minutes
visual analog scale (VAS): self-report scale used to measure anxiety (0 not at all anxious - 7 extremely anxious)
Measured: 15 minutes
Visual Analog Scales (VAS) - Anxious - 45 Minutes
visual analog scale (VAS): self-report scale used to measure anxiety (0 not at all anxious - 7 extremely anxious)
Measured: 45 minutes
Visual Analog Scales (VAS) - Anxious - 80 Minutes
visual analog scale (VAS): self-report scale used to measure anxiety (0 not at all anxious - 7 extremely anxious)
Measured: 80 minutes
Visual Analog Scales (VAS) - Anxious - 110 Minutes
visual analog scale (VAS): self-report scale used to measure anxiety (0 not at all anxious - 7 extremely anxious)
Measured: 110 minutes
Visual Analog Scales (VAS) - Anxious - 170 Minutes
visual analog scale (VAS): self-report scale used to measure anxiety (0 not at all anxious - 7 extremely anxious)
Measured: 170 minutes
Visual Analog Scales (VAS) - Anxious - 230 Minutes
visual analog scale (VAS): self-report scale used to measure anxiety (0 not at all anxious - 7 extremely anxious)
Measured: 230 minutes
Clinician Administered Dissociative Symptoms Scale - Patient Rated - Baseline
Clinician Administered Dissociative Symptoms Scale (CADSS) is a patient and Clinician rated measurement of dissociative states induced by thiopental (0 not at all dissociative - 84 extreme dissociative)
Measured: Baseline
Clinician Administered Dissociative Symptoms Scale - Patient Rated - 15 Minutes
Clinician Administered Dissociative Symptoms Scale (CADSS) is a patient and Clinician rated measurement of dissociative states induced by thiopental (0 not at all dissociative - 84 extreme dissociative)
Measured: 15 minutes
Clinician Administered Dissociative Symptoms Scale - Patient Rated - 80 Minutes
Clinician Administered Dissociative Symptoms Scale (CADSS) is a patient and Clinician rated measurement of dissociative states induced by thiopental (0 not at all dissociative - 84 extreme dissociative)
Measured: 80 minutes
Clinician Administered Dissociative Symptoms Scale - Patient Rated - 110 Minutes
Clinician Administered Dissociative Symptoms Scale (CADSS) is a patient and Clinician rated measurement of dissociative states induced by thiopental (0 not at all dissociative - 84 extreme dissociative)
Measured: 110 minutes
Clinician Administered Dissociative Symptoms Scale - Clinician Rated - Baseline
Clinician Administered Dissociative Symptoms Scale (CADSS) is a patient and Clinician rated measurement of dissociative states induced by thiopental (0 not at all dissociative - 20 extreme dissociative)
Measured: Baseline
Clinician Administered Dissociative Symptoms Scale - Clinician Rated - 15 Minutes
Clinician Administered Dissociative Symptoms Scale (CADSS) is a patient and Clinician rated measurement of dissociative states induced by thiopental (0 not at all dissociative - 20 extreme dissociative)
Measured: 15 minutes
Clinician Administered Dissociative Symptoms Scale - Clinician Rated - 80 Minutes
Clinician Administered Dissociative Symptoms Scale (CADSS) is a patient and Clinician rated measurement of dissociative states induced by thiopental (0 not at all dissociative - 20 extreme dissociative)
Measured: 80 minutes
Clinician Administered Dissociative Symptoms Scale - Clinician Rated - 110 Minutes
Clinician Administered Dissociative Symptoms Scale (CADSS) is a patient and Clinician rated measurement of dissociative states induced by thiopental (0 not at all dissociative - 20 extreme dissociative)
Measured: 110 minutes
Pegboard Task - Baseline (Dominant Hand)
The pegboard task is a measure of coordination that measures reaction time; how long a subject takes to insert pegs into a pegboard puzzle, first using their dominant hand then using their non-dominant hand. A quicker time indicates greater coordination. Scores are timed in seconds
Measured: Baseline
Pegboard Task - 15 Minutes (Dominant Hand)
The pegboard task is a measure of coordination that measures reaction time; how long a subject takes to insert pegs into a pegboard puzzle, first using their dominant hand then using their non-dominant hand. A quicker time indicates greater coordination. Scores are timed in seconds
Measured: 15 minutes
Pegboard Task - Baseline (Non-Dominant Hand)
The pegboard task is a measure of coordination that measures reaction time; how long a subject takes to insert pegs into a pegboard puzzle, first using their dominant hand then using their non-dominant hand. A quicker time indicates greater coordination. Scores are timed in seconds.
Measured: Baseline
Pegboard Task - 15 Minutes (Non-Dominant Hand)
The pegboard task is a measure of coordination that measures reaction time; how long a subject takes to insert pegs into a pegboard puzzle, first using their dominant hand then using their non-dominant hand. A quicker time indicates greater coordination. Scores are timed in seconds.
Measured: 15 minutes
Hopkins Verbal Learning Task (HVLT) - Total Recall
Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function based on word recall. (0 = no words recalled - 36 = all words recalled)
Measured: 15 minutes
Hopkins Verbal Learning Task (HVLT) - Delayed Recall
Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function with word recall at 30 minutes) (0 no words recalled - 12 all words recalled)
Measured: 45 minutes
Verbal Fluency
Verbal Fluency Task: requires subjects to generate as many words as possible beginning with a single letter (e.g., "H") during a one-minute interval. (total words in one-minute interval)
Measured: 15 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2008 (estimated)
- Study startNov 2005
- Primary completionApr 2012
- Study completionApr 2012
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
- Health services research
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 73 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- VA Connecticut Healthcare System
- Responsible party
- Sponsor
- Investigators
- Ismene L Petrakis, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00611767
- Sponsor's protocol ID
- 0510000664
- Other IDs
- VA Merit Grant
- Status last verified
- Nov 2016
- First submitted
- 27 Dec 2007
- Last updated
- 17 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Petrakis IL, Kerfoot K, Pittman B, Perrino A, Koretski J, Newcomb J, Limoncelli D, Acampora G, Ralevski E. Subjective Effects of Thiopental in Young Adults with and without a Family History of Alcoholism. J Addict Res Ther. 2012 May 14;Suppl 7(2):6336. doi: 10.4172/2155-6105.S7-002.
PubMed 24273687
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gamma-Aminobutyric Acid (GABA) Mechanisms Underlying the Vulnerability to Alcohol Dependence
- ClinicalTrials.gov ID
- NCT00611767
- Acronym / sponsor ID
- 0510000664
- Conditions
- Alcoholism
- Keywords
- Thiopental, Alcohol, Family History, Vulnerability, GABA
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 73 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- VA Connecticut Healthcare System
- Study start
- Nov 2005
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 11 Feb 2008 (estimated)
- Results
- Posted 17 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Project will explore the hypothesis that individuals with a family history positive for alcohol dependence (without any current Axis I disorder, except nicotine dependence), experience an alteration in the reward "valence" (balance of positive and negative effects) of the GABAA receptor agonist barbiturate (thiopental) compared to family history negative age-matched subjects. Further, variation in genes involved in brain GABA function may influence the risk for alcoholism by altering a component of the discriminative stimulus effects of ethanol.
Detailed description
This project will explore the hypothesis that individuals with a family history positive for alcohol dependence (FHP) (without any current DSM-IV Axis I disorder, except nicotine dependence), experience an alteration in the reward "valence" (balance of positive and negative effects) of the GABA-A receptor agonist barbiturate (thiopental) compared to family history negative (FHN) age-matched subjects. Further, the effect of variations in genes important in regulating brain GABA function may alter a component of the discriminative stimulus effects of ethanol. FHP individuals are defined as individuals with at least one first-degree relative and another first- or second-degree relatives. Preliminary results suggest that FHP individuals showed an attenuated response to thiopental as measured by the descending limb of the BAES during thiopental infusion relative to the FHN group. Further, preliminary results suggest that variation in genes involved in brain GABA function, glutamate decarboxylase-65 (GAD65), may influence the risk for alcoholism by altering a component of the discriminative stimulus effects of ethanol.
We plan to recruit 2 groups of healthy subjects between the ages of 21-30, one with a family history of alcoholism (family history positive=FHP) and a sex-matched control group without a family history of alcoholism (family history negative=FHN), to undergo two test days scheduled 3 days apart, in a randomized double-blind fashion. Test days will involve a 60-minute intravenous infusion of each of 2 conditions: saline or thiopental, in a randomized order under double-blind conditions. Behavioral ratings include the Biphasic Alcohol Effects Scale (BAES) and Visual Analog Scales (VAS). Exploratory measures include event-related potential recordings (ERP) and measures of eye-to-hand coordination. Blood will be collected for Deoxyribonucleic acid (DNA) extraction and genotyping.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Family History Negative for Alcoholism | Active comparator | Drug: ThiopentalFamily History Negative for Alcoholism subjects will receive 2 interventions |
| Family History Positive for Alcoholism | Placebo comparator | Drug: PlaceboFamily History Positive for Alcoholism subjects will receive 2 interventions |
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, Electrocardiogram (EKG), screening laboratories
- absence of any evidence of substance abuse (with the exception of nicotine dependence) on the basis of history and drug and ethanol-free at the time of testing based on urine toxicology and breath alcohol levels at screening and on each test day.
Key exclusion criteria (5 listed)
- Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) Axis I psychiatric and substance abuse or dependence diagnosis by history on psychiatric evaluation that includes a structured diagnostic interview (SCID)
- unwillingness to remain alcohol-free for three days prior to each test day;
- for women, positive pregnancy test at screening or intention to engage in unprotected sex during the study and
- alcohol naive. For Family History Positive Subjects: 1) Biological father and another first or second-degree biological relative with history of alcoholism by Family History Assessment Module (FHAM) developed by The Collaborative Study on the Genetics of Alcoholism (COGA).
- For Family History Negative Subjects: NO family history of alcoholism in any first or second-degree relatives. Subjects must reliably report on three first-degree relatives.
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 |
|---|---|---|
| ThiopentalA 2-day test design involving 2 conditions: saline (Placebo) or Thiopental 1.5mg/kg (loading) with a subsequent infusion rate of 40 mcg/kg/minute (60 minute infusion). | Drug | Family History Negative for Alcoholism |
| PlaceboA 2-day test design involving 2 conditions: saline (Placebo) or Thiopental 1.5mg/kg (loading) with a subsequent infusion rate of 40 mcg/kg/minute (60 minute infusion). | Drug | Family History Positive for Alcoholism |
Primary outcome
Visual Analog Scales of Similarity to Alcohol - Baseline
Time frame: Baseline
Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Visual Analog Scales of Similarity to Alcohol - 15 Minutes
Time frame: 15 minutes
Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Visual Analog Scales of Similarity to Alcohol - 45 Minutes
Time frame: 45 minutes
Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Visual Analog Scales of Similarity to Alcohol - 80 Minutes
Time frame: 80 minutes
Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Visual Analog Scales of Similarity to Alcohol - 110 Minutes
Time frame: 110 minutes
Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Visual Analog Scales of Similarity to Alcohol - 170 Minutes
Time frame: 170 minutes
Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Visual Analog Scales of Similarity to Alcohol - 230 Minutes
Time frame: 230 minutes
Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
71 secondary outcomes
Number of Drinks Felt Consumed at Baseline
Time frame: Baseline
Number of Drinks Felt Consumed - 15 Minutes
Time frame: 15 minutes
Number of Drinks Felt Consumed - 45 Minutes
Time frame: 45 minutes
Number of Drinks Felt Consumed - 80 Minutes
Time frame: 80 minutes
Number of Drinks Felt Consumed - 110 Minutes
Time frame: 110 minutes
Number of Drinks Felt Consumed - 170 Minutes
Time frame: 170 minutes
Number of Drinks Felt Consumed - 230 Minutes
Time frame: 230 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - Baseline
Time frame: Baseline
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 15 Minutes
Time frame: 15 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 45 Minutes
Time frame: 45 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 80 Minutes
Time frame: 80 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant- 110 Minutes
Time frame: 110 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 170 Minutes
Time frame: 170 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 230 Minutes
Time frame: 230 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative Baseline
Time frame: Baseline
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 15 Minutes
Time frame: 15 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 45 Minutes
Time frame: 45 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 80 Minutes
Time frame: 80 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 110 Minutes
Time frame: 110 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 170 Minutes
Time frame: 170 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 230 Minutes
Time frame: 230 minutes
Visual Analog Scales (VAS) - High - Baseline
Time frame: Baseline
Visual Analog Scales (VAS) - High - 15 Minutes
Time frame: 15 minutes
Visual Analog Scales (VAS) - High - 45 Minutes
Time frame: 45 minutes
Visual Analog Scales (VAS) - High - 80 Minutes
Time frame: 80 minutes
Visual Analog Scales (VAS) - High - 110 Minutes
Time frame: 110 minutes
Visual Analog Scales (VAS) - High - 170 Minutes
Time frame: 170 minutes
Visual Analog Scales (VAS) - High - 230 Minutes
Time frame: 230 minutes
Visual Analog Scales (VAS) - Buzzed - Baseline
Time frame: Baseline
Visual Analog Scales (VAS) - Buzzed - 15 Minutes
Time frame: 15 minutes
Visual Analog Scales (VAS) - Buzzed - 45 Minutes
Time frame: 45 minutes
Visual Analog Scales (VAS) - Buzzed - 80 Minutes
Time frame: 80 minutes
Visual Analog Scales (VAS) - Buzzed - 110 Minutes
Time frame: 110 minutes
Visual Analog Scales (VAS) - Buzzed - 170 Minutes
Time frame: 170 minutes
Visual Analog Scales (VAS) - Buzzed - 230 Minutes
Time frame: 230 minutes
Visual Analog Scales (VAS) - Drowsy - Baseline
Time frame: Baseline
Visual Analog Scales (VAS) - Drowsy - 15 Minutes
Time frame: 15 minutes
Visual Analog Scales (VAS) - Drowsy - 45 Minutes
Time frame: 45 minutes
Visual Analog Scales (VAS) - Drowsy - 80 Minutes
Time frame: 80 minutes
Visual Analog Scales (VAS) - Drowsy - 110 Minutes
Time frame: 110 minutes
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24273687Petrakis IL, Kerfoot K, Pittman B, Perrino A, Koretski J, Newcomb J, Limoncelli D, Acampora G, Ralevski E. Subjective Effects of Thiopental in Young Adults with and without a Family History of Alcoholism. J Addict Res Ther. 2012 May 14;Suppl 7(2):6336. doi: 10.4172/2155-6105.S7-002.
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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 testing Thiopental in people with 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 5 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 17 Mar 2017. 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. Some participants in this study may receive a placebo. 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 17 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?
Visual Analog Scales of Similarity to Alcohol - Baseline (time frame: Baseline). The study lists 7 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 NCT00611767, 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 17 Mar 2017.