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Completed

NCT Number: NCT00611767

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.

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Key information

Conditions

Alcoholism Alcohol-Related Disorders Chemically-Induced Disorders Mental Disorders Substance-Related Disorders

Age range

21 year–30 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

VA Connecticut Healthcare System

West Haven, Connecticut, 06516, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

Thiopental

Drug

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).

Placebo

Drug

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).

Primary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

Secondary outcomes

  1. Number of Drinks Felt Consumed at Baseline

    Time frame: Baseline

    The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.

  2. Number of Drinks Felt Consumed - 15 Minutes

    Time frame: 15 minutes

    The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.

  3. Number of Drinks Felt Consumed - 45 Minutes

    Time frame: 45 minutes

    The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.

  4. Number of Drinks Felt Consumed - 80 Minutes

    Time frame: 80 minutes

    The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.

  5. Number of Drinks Felt Consumed - 110 Minutes

    Time frame: 110 minutes

    The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.

  6. Number of Drinks Felt Consumed - 170 Minutes

    Time frame: 170 minutes

    The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.

  7. Number of Drinks Felt Consumed - 230 Minutes

    Time frame: 230 minutes

    The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.

  8. Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - Baseline

    Time frame: Baseline

    Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

  9. Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 15 Minutes

    Time frame: 15 minutes

    Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

  10. Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 45 Minutes

    Time frame: 45 minutes

    Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

  11. Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 80 Minutes

    Time frame: 80 minutes

    Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

  12. Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant- 110 Minutes

    Time frame: 110 minutes

    Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

  13. Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 170 Minutes

    Time frame: 170 minutes

    Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

  14. Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 230 Minutes

    Time frame: 230 minutes

    Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

  15. Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative Baseline

    Time frame: Baseline

    Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

  16. Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 15 Minutes

    Time frame: 15 minutes

    Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

  17. Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 45 Minutes

    Time frame: 45 minutes

    Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

  18. Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 80 Minutes

    Time frame: 80 minutes

    Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

  19. Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 110 Minutes

    Time frame: 110 minutes

    Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

  20. Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 170 Minutes

    Time frame: 170 minutes

    Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

  21. Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 230 Minutes

    Time frame: 230 minutes

    Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

  22. Visual Analog Scales (VAS) - High - Baseline

    Time frame: Baseline

    visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

  23. Visual Analog Scales (VAS) - High - 15 Minutes

    Time frame: 15 minutes

    visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

  24. Visual Analog Scales (VAS) - High - 45 Minutes

    Time frame: 45 minutes

    visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

  25. Visual Analog Scales (VAS) - High - 80 Minutes

    Time frame: 80 minutes

    visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

  26. Visual Analog Scales (VAS) - High - 110 Minutes

    Time frame: 110 minutes

    visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

  27. Visual Analog Scales (VAS) - High - 170 Minutes

    Time frame: 170 minutes

    visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

  28. Visual Analog Scales (VAS) - High - 230 Minutes

    Time frame: 230 minutes

    visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

  29. Visual Analog Scales (VAS) - Buzzed - Baseline

    Time frame: Baseline

    visual analog scale (VAS): self-report scale used to measure buzzed (0 not at all buzzed - 7 extremely buzzed)

  30. Visual Analog Scales (VAS) - Buzzed - 15 Minutes

    Time frame: 15 minutes

    visual analog scale (VAS): self-report scale used to measure buzzed (0 not at all buzzed - 7 extremely buzzed)

  31. Visual Analog Scales (VAS) - Buzzed - 45 Minutes

    Time frame: 45 minutes

    visual analog scale (VAS): self-report scale used to measure buzzed (0 not at all buzzed - 7 extremely buzzed)

  32. Visual Analog Scales (VAS) - Buzzed - 80 Minutes

    Time frame: 80 minutes

    visual analog scale (VAS): self-report scale used to measure buzzed (0 not at all buzzed - 7 extremely buzzed)

    .

  33. Visual Analog Scales (VAS) - Buzzed - 110 Minutes

    Time frame: 110 minutes

    visual analog scale (VAS): self-report scale used to measure buzzed (0 not at all buzzed - 7 extremely buzzed)

  34. Visual Analog Scales (VAS) - Buzzed - 170 Minutes

    Time frame: 170 minutes

    visual analog scale (VAS): self-report scale used to measure buzzed (0 not at all buzzed - 7 extremely buzzed)

  35. Visual Analog Scales (VAS) - Buzzed - 230 Minutes

    Time frame: 230 minutes

    visual analog scale (VAS): self-report scale used to measure buzzed (0 not at all buzzed - 7 extremely buzzed)

  36. Visual Analog Scales (VAS) - Drowsy - Baseline

    Time frame: Baseline

    visual analog scale (VAS): self-report scale used to measure drowsy (0 not at all drowsy - 7 extremely drowsy)

  37. Visual Analog Scales (VAS) - Drowsy - 15 Minutes

    Time frame: 15 minutes

    visual analog scale (VAS): self-report scale used to measure drowsy (0 not at all drowsy - 7 extremely drowsy)

  38. Visual Analog Scales (VAS) - Drowsy - 45 Minutes

    Time frame: 45 minutes

    visual analog scale (VAS): self-report scale used to measure drowsy (0 not at all drowsy - 7 extremely drowsy)

    .

  39. Visual Analog Scales (VAS) - Drowsy - 80 Minutes

    Time frame: 80 minutes

    visual analog scale (VAS): self-report scale used to measure drowsy (0 not at all drowsy - 7 extremely drowsy)

  40. Visual Analog Scales (VAS) - Drowsy - 110 Minutes

    Time frame: 110 minutes

    visual analog scale (VAS): self-report scale used to measure drowsy (0 not at all drowsy - 7 extremely drowsy)

  41. Visual Analog Scales (VAS) - Drowsy - 170 Minutes

    Time frame: 170 minutes

    visual analog scale (VAS): self-report scale used to measure drowsy (0 not at all drowsy - 7 extremely drowsy)

  42. Visual Analog Scales (VAS) - Drowsy - 230 Minutes

    Time frame: 230 minutes

    visual analog scale (VAS): self-report scale used to measure drowsy (0 not at all drowsy - 7 extremely drowsy)

  43. Visual Analog Scales (VAS) - Depressed - Baseline

    Time frame: Baseline

    visual analog scale (VAS): self-report scale used to measure depressed (0 not at all depressed - 7 extremely depressed)

  44. Visual Analog Scales (VAS) - Depressed - 15 Minutes

    Time frame: 15 minutes

    visual analog scale (VAS): self-report scale used to measure depressed (0 not at all depressed - 7 extremely depressed)

  45. Visual Analog Scales (VAS) - Depressed - 45 Minutes

    Time frame: 45 minutes

    visual analog scale (VAS): self-report scale used to measure depressed (0 not at all depressed - 7 extremely depressed)

  46. Visual Analog Scales (VAS) - Depressed - 80 Minutes

    Time frame: 80 minutes

    visual analog scale (VAS): self-report scale used to measure depressed (0 not at all depressed - 7 extremely depressed)

  47. Visual Analog Scales (VAS) - Depressed - 110 Minutes

    Time frame: 110 minutes

    visual analog scale (VAS): self-report scale used to measure depressed (0 not at all depressed - 7 extremely depressed)

  48. Visual Analog Scales (VAS) - Depressed - 170 Minutes

    Time frame: 170 minutes

    visual analog scale (VAS): self-report scale used to measure depressed (0 not at all depressed - 7 extremely depressed)

  49. Visual Analog Scales (VAS) - Depressed - 230 Minutes

    Time frame: 230 minutes

    visual analog scale (VAS): self-report scale used to measure depressed (0 not at all depressed - 7 extremely depressed)

  50. Visual Analog Scales (VAS) - Anxious - Baseline

    Time frame: Baseline

    visual analog scale (VAS): self-report scale used to measure anxiety (0 not at all anxious - 7 extremely anxious)

  51. Visual Analog Scales (VAS) - Anxious - 15 Minutes

    Time frame: 15 minutes

    visual analog scale (VAS): self-report scale used to measure anxiety (0 not at all anxious - 7 extremely anxious)

  52. Visual Analog Scales (VAS) - Anxious - 45 Minutes

    Time frame: 45 minutes

    visual analog scale (VAS): self-report scale used to measure anxiety (0 not at all anxious - 7 extremely anxious)

  53. Visual Analog Scales (VAS) - Anxious - 80 Minutes

    Time frame: 80 minutes

    visual analog scale (VAS): self-report scale used to measure anxiety (0 not at all anxious - 7 extremely anxious)

  54. Visual Analog Scales (VAS) - Anxious - 110 Minutes

    Time frame: 110 minutes

    visual analog scale (VAS): self-report scale used to measure anxiety (0 not at all anxious - 7 extremely anxious)

  55. Visual Analog Scales (VAS) - Anxious - 170 Minutes

    Time frame: 170 minutes

    visual analog scale (VAS): self-report scale used to measure anxiety (0 not at all anxious - 7 extremely anxious)

  56. Visual Analog Scales (VAS) - Anxious - 230 Minutes

    Time frame: 230 minutes

    visual analog scale (VAS): self-report scale used to measure anxiety (0 not at all anxious - 7 extremely anxious)

  57. Clinician Administered Dissociative Symptoms Scale - Patient Rated - Baseline

    Time frame: 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)

  58. Clinician Administered Dissociative Symptoms Scale - Patient Rated - 15 Minutes

    Time frame: 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)

  59. Clinician Administered Dissociative Symptoms Scale - Patient Rated - 80 Minutes

    Time frame: 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)

  60. Clinician Administered Dissociative Symptoms Scale - Patient Rated - 110 Minutes

    Time frame: 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)

  61. Clinician Administered Dissociative Symptoms Scale - Clinician Rated - Baseline

    Time frame: 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)

  62. Clinician Administered Dissociative Symptoms Scale - Clinician Rated - 15 Minutes

    Time frame: 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)

  63. Clinician Administered Dissociative Symptoms Scale - Clinician Rated - 80 Minutes

    Time frame: 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)

  64. Clinician Administered Dissociative Symptoms Scale - Clinician Rated - 110 Minutes

    Time frame: 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)

  65. Pegboard Task - Baseline (Dominant Hand)

    Time frame: Baseline

    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

  66. Pegboard Task - 15 Minutes (Dominant Hand)

    Time frame: 15 minutes

    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

  67. Pegboard Task - Baseline (Non-Dominant Hand)

    Time frame: Baseline

    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.

  68. Pegboard Task - 15 Minutes (Non-Dominant Hand)

    Time frame: 15 minutes

    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.

  69. Hopkins Verbal Learning Task (HVLT) - Total Recall

    Time frame: 15 minutes

    Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function based on word recall. (0 = no words recalled - 36 = all words recalled)

  70. Hopkins Verbal Learning Task (HVLT) - Delayed Recall

    Time frame: 45 minutes

    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)

  71. Verbal Fluency

    Time frame: 15 minutes

    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)

Sponsors and collaborators

Lead sponsor

Yale University

Other

Collaborators

  • VA Connecticut Healthcare System

Registry information

Official study title

Gamma-Aminobutyric Acid (GABA) Mechanisms Underlying the Vulnerability to Alcohol Dependence

Important dates

Study start
2005
Primary completion
2012
Study completion
2012
First posted
Feb 11, 2008
Registry last updated
Mar 17, 2017

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View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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