Nicotinic Receptor Genetic Variation and Alcohol Reward

NCT03294460 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 17017117-AA-0171
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alcohol Drinking

Keywords

Functional Magnetic Resonance Imaging (fMRI); Alcohol Use; Polymorphism, Genetic; Magnetic Resonance Imaging (MRI); Smoking

Outcome Measures

Primary Outcomes (2)

• 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.

  3 hours

• 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.

  3 hours

Secondary Outcomes (3)

• 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.

  3 hours

• 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.

  3 hours

• 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...

  3 hours

Study Arms (1)

1

EXPERIMENTAL

Alcohol self-administration (IV ethanol for sessions 1 and oral for session 2)

Drug: Alcohol (Oral); Drug: Alcohol (IV); Drug: Alcohol (Ethanol)

Interventions

Alcohol (Ethanol) DRUG

IV and Oral Self-administration

1

Alcohol (Oral) DRUG

Oral Self-administration

1

Alcohol (IV) DRUG

IV Self-administration

1

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• Male and female participants between 21-60 years of age. \[assessment: identification provided to Clinical Center Admissions office\]
• Smoking status:
• 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.\[assessment: smoking history questionnaire, Additional medical history\]
• Non-English speaking individuals. Justification: The study materials, MRI tasks and
• assessments (including the outcome measures) are validated only in English language.
• Current or prior history of major medical illness, including CNS, cardiovascular, respiratory, gastrointestinal, hepatic, renal, endocrine, or reproductive disorders. Justification: Many illnesses may alter the neuropsychological effects of alcohol as well as MRI measures. \[assessment: clinically significant findings on medical history and physical exam, ECG, laboratory tests\]
• Positive hepatitis \[A, B antigen, or C\], or HIV test at screening. Justification: Hepatitis can alter liver function and alcohol pharmacokinetics. HIV infection can alter brain function. \[assessment: laboratory tests\]
• Current \[past 12 months\] history of psychiatric disorders, including depressive disorder, bipolar disorder, or anxiety disorders. Justification: Concurrent psychopathology can alter brain function and alcohol response. \[assessment: SCID interview\]
• Lifetime history of psychotic disorders, obsessive compulsive disorder \[OCD\], post-traumatic stress disorder \[PTSD\], or eating disorder. Justification: These disorders can have long-term effects on brain function and alcohol response. \[assessment: SCID interview\]
• Currently seeking treatment for alcohol use disorders. Justification: It would be unethical to administer alcohol to individuals seeking treatment for alcohol problems. Also, this study does not provide treatment for individuals with alcohol use disorder. \[assessment: medical history\]
• Non-drinkers \[alcohol-naive individuals or current abstainers\] or individuals with no experience drinking 5 or more drinks on one occasion in their lifetime. Justification: It would be unethical to administer alcohol to individuals that do not drink alcohol. \[assessment: Timeline Follow Back, Lifetime Drinking History, Additional History Form and medical history\]
• Positive result on urine drug screen or positive breathalyzer during screening visit. Positive urine drug screen or breathalyzer reading during more than 1 study visit will result in participant withdrawal from the study. Justification: Current or recent exposure to alcohol or drugs of abuse could impact brain function and alcohol response. \[assessment: laboratory tests and breathalyzer test.
• Current or prior history of alcohol-induced flushing reactions, including rapid reddening of the face, rapid heart rate and breathing, and nausea after 1 or 2 drinks. Justification: It would not be safe to administer alcohol to individuals with the highly aversive flushing response to alcohol. \[assessment: alcohol flushing questionnaire\]
• Use of prescription or OTC medications known to interact with alcohol 2 weeks prior to screening or screening update visit. 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 famotidine, cimetidine and ranitidine; muscle relaxants; anti-epileptics including phenytoin and phenobarbital; codeine and opioid analgesics including Darvocet, Percocet and hydrocodone;

Sponsors & Collaborators

• National Institute on Alcohol Abuse and Alcoholism (NIAAA): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Alcohol Drinking; Smoking

Interventions

Ethanol

Condition Hierarchy (Ancestors)

Drinking Behavior; Behavior

Intervention Hierarchy (Ancestors)

Alcohols; Organic Chemicals

Study Officials

• Vijay A Ramchandani, Ph.D.

  National Institute on Alcohol Abuse and Alcoholism (NIAAA)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vijay A Ramchandani, Ph.D.

CONTACT

(301) 402-8527; vijayr@mail.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2017
• First Posted: September 27, 2017
• Study Start: June 10, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 15, 2026

Record last verified: 2026-04-09

Locations

US (1)