Nicotinic Receptor Genetic Variation and Alcohol Reward
ConditionAlcohol Drinking
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age21-60
SponsorNational Institute on Alcohol Abuse and Alcoholism (NIAAA)
About this trial
Background:
People with the brain disease AUD (alcohol use disorder) have a serious problem with drinking. Researchers want to study how different people react to alcohol, and how genes affect this. They will focus on a nicotine receptor gene that may increase a person s AUD risk.
Objectives:
To see if people with variations of a nicotine receptor gene take alcohol differently and have different brain responses to alcohol cues.
Eligibility:
Healthy adults ages 21 - 60. This study includes smokers and non-smokers.
Design:
Participation will be based on evaluation under the NIAAA natural history protocol (14-AA-0181) or a screening visit under this protocol.
Participants will have two 9-hour visits. They must have no alcohol or non-prescription drugs before all visits and no food or drink before the first visit.
At every visit, participants will:
* Get a light meal * Have breath and urine tests * Get taxi rides there and back
At visits 1, participants will:
* Have a thin plastic tube inserted in an arm and connected to a pump for alcohol infusion. * Have sensors on their chest to monitor heart rate. * Sit in a chair for 2.5 hours and get alcohol by pushing a button. Their breath alcohol level will be monitored. * Answer questions about mood and effects of alcohol * Give blood samples * Relax at the clinic while their breath alcohol level drops
At visit 2, participants will:
* Answer questions and do computer tests * Have an alcoholic drink and a snack * Have a magnetic resonance imaging (MRI) scan. They will lie in a machine that takes pictures of the brain. They will do computer tasks. * Have another drink and snack * Relax until their alcohol level drops
Participants will have a follow-up call after each visit.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
This study will include healthy male and female participants from the general population prospectively genotyped to obtain balanced samples of four groups of participants based on their smoking status (smokers and non-smokers) and CHRNA5 rs16969968 genotype: 1). A-allele carriers (AA or AG genotype), and 2). G-allele homozygotes (GG genotype). The study will be open to all racial and ethnic groups, as long as the individual meets the genotype criteria.
Disqualifiers
Male and female participants between 21-60 years of age. [assessment: identification provided to Clinical Center Admissions office]
Smokers will have a history of at least 1 year of daily smoking, defined as individuals who smoke more than 20 uses of nicotinic products/week on average, and a cotinine level, measured by the NarcoCheck PreDosage Nicotine Test [PNT] test, of >= 2. [assessment: Smoking history questionnaire, Additional medical history, PreDosage Nicotine test]
Non-smokers with no history of smoking in the past year and less than 20 uses of nicotinic products lifetime.[assessment: smoking history questionnaire, Additional medical history]
Inclusion criteria for women: Use of adequate method of birth control during the study, if female is sexually active and is not surgically sterilized. Adequate methods of contraception include: use of oral contraceptives; use of barrier method of contraceptive; use of an approved IUD or other long-acting reversible contraceptive [LARC]; have a male sexual partner who is surgically sterilized; or have exclusively female sexual partner[s]. Justification: To minimize the risk of administering alcohol to pregnant women, given the known effects of alcohol exposure on fetuses. [assessment: medical history]
Trial design
Design model
Single group
Treatments tested in this trial
Alcohol (Oral)
DrugOral Self-administration
Alcohol (IV)
DrugIV Self-administration
Alcohol (Ethanol)
DrugIV and Oral Self-administration
Treatment groups
128 Participants
are divided into 1 treatment groupGroup A: 1Experimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
To examine the effect of CHRNA5 (rs16969968) genetic variation on neural correlates of incentive salience for alcohol, as measured by BOLD response during the Alcohol-Food Incentive Delay (AFID) task using fMRI.
The following measures will be examined as a function of smoking status (smokers and non-smokers) and CHRNA5 genotype. The influence of sex, age, and recent drinking history will be examined as covariates. Primary outcome measures include: (1a) BrAC exposure (peak BrAC, number of infusions, time to binge-level BrAC) during the free-access IV-ASA; (1b) BOLD response during the AFID task in neural regions associated with alcohol reward processing, including ventral striatum, amygdala, and insula. Secondary outcome measures include: (2a) resting state functional connectivity (rsFC) between the regions associated with the salience network, including dorsal anterior cingulate cortex, ventral striatum, and extended amygdala; (2b) preferred rate of self-infusion during the second IV-ASA session.
Time frame
3 hours2
To examine the effect of CHRNA5 (rs16969968) genetic variation on IV alcohol self-administration, as measured by BrAC exposure (peak BrAC, number of infusions, time to binge-level) in non-smoking, non-dependent drinkers.
The following measures will be examined as a function of smoking status (smokers and non-smokers) and CHRNA5 genotype. The influence of sex, age, and recent drinking history will be examined as covariates. Primary outcome measures include: (1a) BrAC exposure (peak BrAC, number of infusions, time to binge-level BrAC) during the free-access IV-ASA; (1b) BOLD response during the AFID task in neural regions associated with alcohol reward processing, including ventral striatum, amygdala, and insula. Secondary outcome measures include: (2a) resting state functional connectivity (rsFC) between the regions associated with the salience network, including dorsal anterior cingulate cortex, ventral striatum, and extended amygdala; (2b) preferred rate of self-infusion during the second IV-ASA session.
Time frame
3 hoursSecondary outcomes
1
To examine the relationship between fMRI measures (BOLD response during AFID and rsFC measures) and IV alcohol self-administration, and any differences in the degree of association among these measures by CHRNA5 genotype.
Time frame
3 hours2
To examine the effect of CHRNA5 (rs16969968) genetic variation on the rate of IV alcohol self-administration, as measured by the preferred rate during the second IV-ASA session in non-smoking, non-dependent drinkers.
Time frame
3 hours3
To examine the effect of CHRNA5 (rs16969968) genetic variation on resting-state functional connectivity (rsFC) among brain regions associated with the salience network, including dorsal anterior cingulate cortex, ventral striatum and extended am...
Time frame
3 hoursSponsors and contacts
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Source ClinicalTrials.gov