Genetics of the Acute Response to Alcohol in Social Drinkers
| Status: | Terminated |
|---|---|
| Conditions: | Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 21 - 30 |
| Updated: | 4/6/2019 |
| Start Date: | May 26, 2011 |
| End Date: | January 20, 2016 |
Genetics of the Acute Response to Alcohol in Humans
Background:
- Previous research has shown that a person s genes can influence how they respond to
alcohol. But researchers do not yet know all the genes that might be involved.
Objectives:
- To identify genes that are related to how non-alcoholic individuals respond to alcohol.
Eligibility:
- Healthy people between 21 and 30 years of age who have no history of alcohol or drug
dependence.
Design:
- The study requires one or two 9-hour visits to the National Institutes of Health
Clinical Center.
- Participants must not take any medicines (except birth-control pills for women) for at
least 3 days before the visit. They must not drink alcohol for at least 2 days before
the visit.
- Screening includes a medical history, physical exam, and a urine test for drugs of
abuse.
- Participants will be given alcohol over about 2.5 hours. This will have about the same
effect as having three to four drinks. Frequent breathalyzer tests will check breath
alcohol level during the infusion.
- Before and during the infusion, participants will complete questionnaires about mood and
feelings. Other tests will study thinking, balance, judgment, and risk-taking. Blood
samples will be collected four times during the infusion.
- Participants will have breakfast at the start of the visit (around 8:00 AM). They will
have a snack before the start of the alcohol infusion (around 10:45 AM). Lunch will be
served after the alcohol infusion is complete (around 2:20 PM). After the tests, those
in the study will have to stay in the Clinical Center until their breath alcohol level
falls below 0.02%. This can take up to 2.5 hours. A final blood sample will be drawn at
that time. Participants will not be able to drive themselves home after the study
visits. Also, they should not take any medicines or operate any machinery for at least 2
hours after leaving NIH.
- Previous research has shown that a person s genes can influence how they respond to
alcohol. But researchers do not yet know all the genes that might be involved.
Objectives:
- To identify genes that are related to how non-alcoholic individuals respond to alcohol.
Eligibility:
- Healthy people between 21 and 30 years of age who have no history of alcohol or drug
dependence.
Design:
- The study requires one or two 9-hour visits to the National Institutes of Health
Clinical Center.
- Participants must not take any medicines (except birth-control pills for women) for at
least 3 days before the visit. They must not drink alcohol for at least 2 days before
the visit.
- Screening includes a medical history, physical exam, and a urine test for drugs of
abuse.
- Participants will be given alcohol over about 2.5 hours. This will have about the same
effect as having three to four drinks. Frequent breathalyzer tests will check breath
alcohol level during the infusion.
- Before and during the infusion, participants will complete questionnaires about mood and
feelings. Other tests will study thinking, balance, judgment, and risk-taking. Blood
samples will be collected four times during the infusion.
- Participants will have breakfast at the start of the visit (around 8:00 AM). They will
have a snack before the start of the alcohol infusion (around 10:45 AM). Lunch will be
served after the alcohol infusion is complete (around 2:20 PM). After the tests, those
in the study will have to stay in the Clinical Center until their breath alcohol level
falls below 0.02%. This can take up to 2.5 hours. A final blood sample will be drawn at
that time. Participants will not be able to drive themselves home after the study
visits. Also, they should not take any medicines or operate any machinery for at least 2
hours after leaving NIH.
Previous research, including our prior studies using the alcohol clamp, has shown substantial
genetic influences on alcohol pharmacokinetics and pharmacodynamics. While the influence of
several individual genes on alcohol pharmacokinetics and pharmacodynamics has been examined,
there has not been a comprehensive evaluation of genetic influences on the pharmacokinetics
and pharmacodynamics of alcohol in humans.
Objectives: To evaluate the genetic underpinnings of the pharmacodynamics of alcohol using
candidate gene analysis of measures of the initial and adaptive acute response to alcohol in
humans.
Study Population: Subjects will be 21-30 year-old non-smoking, male and female non-dependent
drinkers in good health, as determined by medical history, physical exam, and ECG and lab
tests. Subjects with Axis-I psychiatric diagnoses, including alcohol or substance dependence,
will be excluded.
Design: The study will be conducted in two phases. In phase I, 40 subjects (20 with positive
family history of alcoholism (FHP) and 20 with no family history of alcoholism (FHN)) will
undergo two ethanol infusion sessions to compare different breath alcohol concentration
exposures. In one session (Clamp session), participants will be infused with 6% ethanol in
saline using an individualized infusion profile to achieve and clamp breath alcohol
concentrations (BrAC) at 60 mg% for 2 hours. In the other session (Oral-mimic session),
participants will be infused with 6% ethanol and saline using another individualized infusion
profile to achieve a BrAC-time profile that would be typically obtained after oral
administration (ascending limb to peak BrAC followed by descending limb). During each
session, serial BrACs will be obtained, and heart-rate and skin blood flow will be
continuously recorded. A battery of subjective (self-rating questionnaires) and objective
measures (psychomotor performance, behavioral disinhibition tasks) will be obtained at
baseline and two points during the infusion to assess the initial response and adaptive
response to alcohol. The measures of initial response and adaptive response will be compared
between sessions to determine which provides greater sensitivity (higher effect size) for
detecting family history differences.
In phase II, 160 participants will undergo a one session study. Participants will receive an
ethanol infusion to achieve the BrAC-time profile (Clamp or Oral-mimic) that provides the
greater sensitivity to family history of alcoholism in phase I of the study. The same battery
of subjective and objective measures will be obtained to assess the initial response and
adaptive response to alcohol. These response measures will be used as endophenotypes for
examination of genetic association with a set of candidate genes, based on previous clinical
and pre-clinical studies.
Outcome measures: Initial response to alcohol and adaptive response to alcohol measures will
be obtained for a battery of assessments, including subjective ratings of alcohol effects,
psychomotor performance, behavioral disinhibition tasks and autonomic measures.
genetic influences on alcohol pharmacokinetics and pharmacodynamics. While the influence of
several individual genes on alcohol pharmacokinetics and pharmacodynamics has been examined,
there has not been a comprehensive evaluation of genetic influences on the pharmacokinetics
and pharmacodynamics of alcohol in humans.
Objectives: To evaluate the genetic underpinnings of the pharmacodynamics of alcohol using
candidate gene analysis of measures of the initial and adaptive acute response to alcohol in
humans.
Study Population: Subjects will be 21-30 year-old non-smoking, male and female non-dependent
drinkers in good health, as determined by medical history, physical exam, and ECG and lab
tests. Subjects with Axis-I psychiatric diagnoses, including alcohol or substance dependence,
will be excluded.
Design: The study will be conducted in two phases. In phase I, 40 subjects (20 with positive
family history of alcoholism (FHP) and 20 with no family history of alcoholism (FHN)) will
undergo two ethanol infusion sessions to compare different breath alcohol concentration
exposures. In one session (Clamp session), participants will be infused with 6% ethanol in
saline using an individualized infusion profile to achieve and clamp breath alcohol
concentrations (BrAC) at 60 mg% for 2 hours. In the other session (Oral-mimic session),
participants will be infused with 6% ethanol and saline using another individualized infusion
profile to achieve a BrAC-time profile that would be typically obtained after oral
administration (ascending limb to peak BrAC followed by descending limb). During each
session, serial BrACs will be obtained, and heart-rate and skin blood flow will be
continuously recorded. A battery of subjective (self-rating questionnaires) and objective
measures (psychomotor performance, behavioral disinhibition tasks) will be obtained at
baseline and two points during the infusion to assess the initial response and adaptive
response to alcohol. The measures of initial response and adaptive response will be compared
between sessions to determine which provides greater sensitivity (higher effect size) for
detecting family history differences.
In phase II, 160 participants will undergo a one session study. Participants will receive an
ethanol infusion to achieve the BrAC-time profile (Clamp or Oral-mimic) that provides the
greater sensitivity to family history of alcoholism in phase I of the study. The same battery
of subjective and objective measures will be obtained to assess the initial response and
adaptive response to alcohol. These response measures will be used as endophenotypes for
examination of genetic association with a set of candidate genes, based on previous clinical
and pre-clinical studies.
Outcome measures: Initial response to alcohol and adaptive response to alcohol measures will
be obtained for a battery of assessments, including subjective ratings of alcohol effects,
psychomotor performance, behavioral disinhibition tasks and autonomic measures.
- INCLUSION CRITERIA:
Male and female participants between 21-30 years of age.
Good health as determined by medical history, physical exam, EKG and lab tests.
EXCLUSION CRITERIA:
Current or prior history of any disease, including CNS, cardiovascular, respiratory,
gastrointestinal, hepatic, renal, endocrine, or reproductive disorders.
Positive hepatitis or HIV test at screening.
Current (i.e., in the past year) diagnosis of Axis-I psychiatric illness.
Current or lifetime diagnosis of alcohol or substance dependence.
Currently (i.e., in the past year) seeking treatment for alcohol-related problems.
Non-drinkers (alcohol-na(SqrRoot) ve individuals or current abstainers), or individuals who
have never consumed more than 4 drinks on at least one occasion.
Current or prior history of alcohol-induced flushing reaction, including rapid reddening of
the face, rapid heart rate and breathing, and nausea after 1 or 2 drinks.
Regular tobacco users will be excluded from the study in order to avoid nicotine withdrawal
symptoms. Occasional use of tobacco products (up to 20 cigarettes/week, Fagerstrom Test for
Nicotine Dependence Score less than 4) is acceptable.
Positive result on urine drug screen or breathalyzer test at screening
No regular use of medications for the last 3 months. Use of prescription or OTC medications
known to interact with alcohol within 2 weeks of the study. These include, but may not be
limited to: isosorbide, nitroglycerine, benzodiazepines, warfarin, anti-depressants such as
amitriptyline, clomipramine and nefazodone, anti-diabetes medications such as glyburide,
metformin and tolbutamide, H2-antagonists for heartburn such as cimetidine and ranitidine,
muscle relaxants, anti-epileptics including phenytoin and phenobarbital codeine, and
narcotics including darvocet, percocet and hydrocodone. Drugs known to inhibit or induce
enzymes that metabolize alcohol should not be used for 4 weeks prior to the study. These
include chlorzoxazone, isoniazid, metronidazole and disulfiram. Cough-and-cold preparations
which contain anti-histamines, pain medicines and anti-inflammatories such as aspirin,
ibuprofen, acetaminophen, celecoxib and naproxen, should be withheld for at least 72 hours
prior to each study session.
Females must not be pregnant or breast-feeding. Female participants will undergo a urine
beta-hCG test to ensure they are not pregnant during screening and study visits.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Click here to add this to my saved trials
