This study is currently recruiting participants.
Number
17-AA-0171
Sponsoring Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 21 Years Max Age: 60 Years
Referral Letter Required
No
Population Exclusion(s)
Children
Keywords
Functional Magnetic Resonance Imaging (fMRI); Alcohol Use; Polymorphism, Genetic; Magnetic Resonance Imaging (MRI); Smoking
Recruitment Keyword(s)
None
Condition(s)
Alcohol Drinking
Investigational Drug(s)
IV Ethanol
Investigational Device(s)
Intervention(s)
Drug: Alcohol (Oral) Drug: Alcohol (IV) Drug: Alcohol (Ethanol)
Supporting Site
National Institute on Alcohol Abuse and Alcoholism
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.
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INCLUSION CRITERIA: 1. Male and female participants between 21-60 years of age. [assessment: identification provided to Clinical Center Admissions office] 2. 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] 3. 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] EXCLUSION CRITERIA: 1. 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] 2. 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] 3. 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] 4. 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] 5. Current or lifetime diagnosis of alcohol or substance use disorder. Past mild AUD with no current symptoms for atleast 2 years will not be exclusionary. Justification: History of moderate to severe alcohol or substance use disorder will impact brain function and alcohol response. We do not anticipate past mild AUD in remission for 2+ years would have such impact on brain function and alcohol response. We will examine this in our exploratory analysis. [assessment: SCID interview] 6. 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] 7. History of significant withdrawal symptoms or presence of clinically significant withdrawal symptoms [Clinical Institute Withdrawal Assessment [CIWA] score > 8] at screening. Justification: Withdrawal symptoms would be indicative of alcohol use disorder, which is already an exclusion criteria. Additionally, withdrawal symptoms would be a major safety concern for participants, and a major confound in the assessment of alcohol response and brain function. [assessment: CIWA assessment] 8. 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: medical history] 9. 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. 10. 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] 11. Medication exclusion criteria: --Regular use of prescription or OTC medications known to interact with alcohol. 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; regular or prescribed use of anti-histamines, pain medicines, and anti-inflammatories such as aspirin, ibuprofen, acetaminophen, celecoxib, and naproxen. --Use of medications known to inhibit or induce enzymes that metabolize alcohol for 4 weeks prior to screening. These include chlorzoxazone, isoniazid, metronidazole, and disulfiram. --Regular use of drugs known to affect hemodynamic response. These include antihypertensives, insulin, and thyroid medications. Note that any discontinuation of medications will only be done at the recommendation of a physician. [assessment: medical history and physical exam] 12. Exclusion criteria for MRI: -- Left-handedness [Edinburgh Handedness Scale]. Justification: To avoid lateralized effects on brain function measures and reduce potential variance in MRI signals. -- Presence of ferromagnetic objects in the body that are contraindicated for MRI of the head [including but not limited to pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips, metallic prostheses, permanent eyeliner, implanted delivery pump, or shrapnel fragments]. -- Fear of enclosed spaces. Justification: To minimize risk and discomfort. -- Inability to lie comfortable on back for up to 2 hours in the MRI scanner. Justification: To minimize risk and discomfort. [assessment: NIAAA MRI Safety Screening Questionnaire] 13. Exclusion criteria for women: Justification: To minimize the risk of administering alcohol to pregnant or nursing women, given the known effects of alcohol exposure on fetuses and infants. -- Pregnant [assessment: urine beta-hCG test at screening]. Women must also test negative on urine beta-hCG test at the start of every study visit. -- Breast-feeding [assessment: medical history and physical exam].
1. Male and female participants between 21-60 years of age. [assessment: identification provided to Clinical Center Admissions office]
2. 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]
3. 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]
EXCLUSION CRITERIA:
1. 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]
2. 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]
3. 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]
4. 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]
5. Current or lifetime diagnosis of alcohol or substance use disorder. Past mild AUD with no current symptoms for atleast 2 years will not be exclusionary. Justification: History of moderate to severe alcohol or substance use disorder will impact brain function and alcohol response. We do not anticipate past mild AUD in remission for 2+ years would have such impact on brain function and alcohol response. We will examine this in our exploratory analysis. [assessment: SCID interview]
6. 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]
7. History of significant withdrawal symptoms or presence of clinically significant withdrawal symptoms [Clinical Institute Withdrawal Assessment [CIWA] score > 8] at screening. Justification: Withdrawal symptoms would be indicative of alcohol use disorder, which is already an exclusion criteria. Additionally, withdrawal symptoms would be a major safety concern for participants, and a major confound in the assessment of alcohol response and brain function. [assessment: CIWA assessment]
8. 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: medical history]
9. 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.
10. 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]
11. Medication exclusion criteria:
--Regular use of prescription or OTC medications known to interact with alcohol. 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; regular or prescribed use of anti-histamines, pain medicines, and anti-inflammatories such as aspirin, ibuprofen, acetaminophen, celecoxib, and naproxen.
--Use of medications known to inhibit or induce enzymes that metabolize alcohol for 4 weeks prior to screening. These include chlorzoxazone, isoniazid, metronidazole, and disulfiram.
--Regular use of drugs known to affect hemodynamic response. These include antihypertensives, insulin, and thyroid medications.
Note that any discontinuation of medications will only be done at the recommendation of a physician.
[assessment: medical history and physical exam]
12. Exclusion criteria for MRI:
-- Left-handedness [Edinburgh Handedness Scale]. Justification: To avoid lateralized effects on brain function measures and reduce potential variance in MRI signals.
-- Presence of ferromagnetic objects in the body that are contraindicated for MRI of the head [including but not limited to pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips, metallic prostheses, permanent eyeliner, implanted delivery pump, or shrapnel fragments].
-- Fear of enclosed spaces. Justification: To minimize risk and discomfort.
-- Inability to lie comfortable on back for up to 2 hours in the MRI scanner. Justification: To minimize risk and discomfort. [assessment: NIAAA MRI Safety Screening Questionnaire]
13. Exclusion criteria for women: Justification: To minimize the risk of administering alcohol to pregnant or nursing women, given the known effects of alcohol exposure on fetuses and infants.
-- Pregnant [assessment: urine beta-hCG test at screening]. Women must also test negative on urine beta-hCG test at the start of every study visit.
-- Breast-feeding [assessment: medical history and physical exam].
Principal Investigator
Referral Contact
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