Intravenous Alcohol Administration Using BrAc Method in Healthy Subjects With and Without a Family History of Alcoholism

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00612352

Enrollment

180

Registered

2008-02-11

Start date

2001-03-31

Completion date

2015-06-30

Last updated

2021-10-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Alcoholism

Brief 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 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 have decreased 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 alcohol 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 3 test days in a randomized balanced order under double-blind conditions. Test days will involve administration of placebo or one of two ethanol doses (target BrAc=40mg%, or target BrAc=100mg%) intravenously for 20 minutes, until the target BrAc is achieved. Once BrAc is achieved (40mg% or 100mg%) it will be maintained using a clamp procedure for over 60 minutes. Outcome measures include the Positive and Negative Symptom Scale, visual analog scales of mood state, (i.e. anxiety) and the Clinician-Administered Dissociative States Scale (CADSS) to measure perceptual responses to alcohol. Secondary measures include visual analog scales for high, similarity to ethanol, Mini Mental Status Examination (MMSE), Placement of electrodes, Biphasic Alcohol Effects Scale, Hopkins Verbal Learning, and number of drinks scale, aspects of craving for alcohol and tests of cognitive impairment.

Interventions

DRUGEthanol High Dose, Ethanol Low Dose, and Placebo

Three test days will involve administration of placebo, ethanol high dose (BrAc=100mg%) or ethanol low dose (BrAc=40mg%)intravenously for approximately 20 minutes, until the target BrAc is achieved. Once BrAc is achieved (40mg% or 100mg%) it will be maintained using a clamp procedure for 60 minutes.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

OTHER

Masking

DOUBLE (Subject, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

21 Years to 30 Years

Healthy volunteers

Yes

Inclusion criteria

1. Male and female between the ages of 21 and 30 years; 2. medically and neurologically healthy on the basis of history, physical examination, EKG, Screening laboratories absence of current and/or past substance abuse on the basis of history and urine toxicology and breath alcohol levels at screening and on each test day. For Family History Positive (FHP) Subjects: 1) Biological father and another first or second-degree biological relative with history of alcoholism by Family History Assessment Module (FHAM) developed by COGA.

Exclusion criteria

1. DSM-IV psychiatric and substance abuse (excluding alcohol abuse) diagnosis by history on psychiatric evaluation that includes a structured diagnostic interview (Structured Clinical Interview for Diagnostic and Statistical Manual (DSM)-IV Axis I Disorders (SCID)) 2. Subjects who meet criteria for alcohol abuse and express an interest in stopping alcohol use and/or express an interest in treatment or are currently enrolled in treatment for alcoholism, or have sought treatment in the last 6 months. 3. history of counseling or psychotherapy; except family therapy centered around another family member 4. extended unwillingness to remain alcohol-free for 48 hours prior to test days; 5. for women: positive pregnancy test at screening or intention to engage in unprotected sex during the study 6. alcohol naïve 7. Adoptee and no contact with family members.

Design outcomes

Primary

Measure	Time frame	Description
Number of Drinks Felt Consumed at Baseline	Baseline	The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.
Number of Drinks Felt Consumed at 10 Minutes	10 minutes	The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.
Number of Drinks Felt Consumed at 30 Minutes	30 minutes	The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.
Number of Drinks Felt Consumed at 110 Minutes	110 minutes	The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.
Number of Drinks Felt Consumed at 140 Minutes	140 minutes	The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.
Number of Drinks Felt Consumed at 170 Minutes	170 minutes	The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.
Number of Drinks Felt Consumed at 230 Minutes	230 minutes	The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.
Visual Analog Scale of Similarity to Alcohol - Baseline	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 Scale of Similarity to Alcohol -10 Minutes	10 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 Scale of Similarity to Alcohol - 30 Minutes	30 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 Scale of Similarity to Alcohol - 60 Minutes	60 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 Scale of Similarity to Alcohol - 110 Minutes	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 Scale of Similarity to Alcohol - 140 Minutes	140 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 Scale of Similarity to Alcohol - 170 Minutes	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 Scale of Similarity to Alcohol - 230 Minutes	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

Measure	Time frame	Description
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 240 Minutes	240 minutes	Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)
Visual Analog Scale (VAS) HIGH - Baseline	Baseline	visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Visual Analog Scale (VAS) HIGH - 10 Minutes	10 minutes	visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Visual Analog Scale (VAS) HIGH - 30 Minutes	30 minutes	visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Visual Analog Scale (VAS) HIGH - 60 Minutes	60 minutes	visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Visual Analog Scale (VAS) HIGH - 110 Minutes	110 minutes	visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Visual Analog Scale (VAS) HIGH - 140 Minutes	140 minutes	visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Visual Analog Scale (VAS) HIGH - 170 Minutes	170 minutes	visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Visual Analog Scale (VAS) HIGH - 240 Minutes	240 minutes	visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Visual Analog Scale (VAS) Drowsy - Baseline	Baseline	visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)
Visual Analog Scale (VAS) Drowsy - 10 Minutes	10 minutes	visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)
Visual Analog Scale (VAS) Drowsy - 30 Minutes	30 minutes	visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)
Visual Analog Scale (VAS) Drowsy - 60 Minutes	60 minutes	visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)
Visual Analog Scale (VAS) Drowsy - 110 Minutes	110 minutes	visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)
Visual Analog Scale (VAS) Drowsy - 140 Minutes	140 minutes	visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)
Visual Analog Scale (VAS) Drowsy - 170 Minutes	170 minutes	visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)
Visual Analog Scale (VAS) Drowsy - 230 Minutes	230 minutes	visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)
Hopkins Verbal Learning Task - Immediate Recall - Trial 1	30 minutes - Trial 1	Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function. (Three immediate recall trials) (0 no words recalled - 12 all words recalled)
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative Baseline	Baseline	Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Hopkins Verbal Learning Task - Immediate Recall - Trial 3	30 minutes - Trial 3	Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function. (Three immediate recall trials) (0 no words recalled - 12 all words recalled)
Hopkins Verbal Learning Task - Delay Recall	60 minutes	Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function. (Delay Recall: 30 minutes after Trials 1-3 were given) (0 no words recalled - 12 all words recalled)
Pegboard Task - Baseline (Dominant Hand)	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
Pegboard Task - 30 Minutes (Dominant Hand)	30 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.
Pegboard Task - Baseline (Non-Dominant Hand)	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.
Pegboard Task - 30 Minuites (Non-Dominant Hand)	30 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.
Hopkins Verbal Learning Task - Immediate Recall - Trial 2	30 minutes - Trial 2	Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function. (Three immediate recall trials) (0 no words recalled - 12 all words recalled)
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 10 Minutes	10 minutes	Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 30 Minutes	30 minutes	Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 60 Minutes	60 minutes	Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 110 Minutes	110 minutes	Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 140 Minutes	140 minutes	Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 170 Minutes	170 minutes	Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 230 Minutes	230 minutes	Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - Baseline	Baseline	Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 10 Minutes	10 minutes	Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 30 Minutes	30 minutes	Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 60 Minutes	60 minutes	Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 110 Minutes	110 minutes	Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 140 Minutes	140 minutes	Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 170 Minutes	170 minutes	Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

Countries

United States

Participant flow

Participants by arm

Arm	Count
Family History Positive Subjects with a positive family history of alcoholism.	65
Family History Negative Subjects with no family history of alcoholism.	115
Total	180

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	0
Overall Study	didn't return calls/show up on test date	4	1
Overall Study	moved out of state	1	0
Overall Study	Withdrawal by Subject	3	5

Baseline characteristics

Characteristic	Family History Negative	Total	Family History Positive
Age, Continuous	24.1 years STANDARD_DEVIATION 2.38	24.08 years STANDARD_DEVIATION 2.6	24.06 years STANDARD_DEVIATION 2.97
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	14 Participants	24 Participants	10 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	13 Participants	17 Participants	4 Participants
Race (NIH/OMB) White	88 Participants	139 Participants	51 Participants
Sex: Female, Male Female	56 Participants	88 Participants	32 Participants
Sex: Female, Male Male	59 Participants	92 Participants	33 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	1 / 65	0 / 115
serious Total, serious adverse events	0 / 65	0 / 115

Outcome results

Primary

Number of Drinks Felt Consumed at 10 Minutes

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

Time frame: 10 minutes