AlcoholismPhase 1NCT01375556
Genetics of the Acute Response to Alcohol in Social Drinkers
A Phase 1 study testing Ethanol in people with Alcoholism and Genetics, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 to 30 yearsHealthy volunteers can take part
- Conditions the study is for
- Alcoholism, Genetics
- What is being tested?
- Ethanol
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- 26 May 2011to 20 Jan 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 30 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male and female participants between 21-30 years of age.
- Good health as determined by medical history, physical exam, EKG and lab tests.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: 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.
Read more
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.
Read the detailed description
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.
- Conditions
- Alcoholism, Genetics
- Being tested
- Ethanol
- Keywords
- Alcohol Clamp, Pharmacogenetics, Family History of Alcoholism, Pharmacodynamics, Healthy Volunteer, HV
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EthanolDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Initial response to alcohol and adaptive response to alcohol measures for subjective ratings of alcohol effects, psychomotor performance, behavioral disinhibition tasks and autonomic measures
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2011 (estimated)
- Study start26 May 2011
- Primary completion20 Jan 2016
- Study completion20 Jan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for AlcoholismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Sponsor type
- US National Institutes of Health
- Investigators
- Vijay A Ramchandani, Ph.D., Principal investigator, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01375556
- Sponsor's protocol ID
- 110180
- Other IDs
- 11-AA-0180
- Status last verified
- 20 Jan 2016
- First submitted
- 16 Jun 2011
- Last updated
- 29 Nov 2019
- Results posted
- No
Publications
Bernstein DP, Stein JA, Newcomb MD, Walker E, Pogge D, Ahluvalia T, Stokes J, Handelsman L, Medrano M, Desmond D, Zule W. Development and validation of a brief screening version of the Childhood Trauma Questionnaire. Child Abuse Negl. 2003 Feb;27(2):169-90. doi: 10.1016/s0145-2134(02)00541-0.
PubMed 12615092Bierut LJ, Agrawal A, Bucholz KK, Doheny KF, Laurie C, Pugh E, Fisher S, Fox L, Howells W, Bertelsen S, Hinrichs AL, Almasy L, Breslau N, Culverhouse RC, Dick DM, Edenberg HJ, Foroud T, Grucza RA, Hatsukami D, Hesselbrock V, Johnson EO, Kramer J, Krueger RF, Kuperman S, Lynskey M, Mann K, Neuman RJ, Nothen MM, Nurnberger JI Jr, Porjesz B, Ridinger M, Saccone NL, Saccone SF, Schuckit MA, Tischfield JA, Wang JC, Rietschel M, Goate AM, Rice JP; Gene, Environment Association Studies Consortium. A genome-wide association study of alcohol dependence. Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5082-7. doi: 10.1073/pnas.0911109107. Epub 2010 Mar 2.
PubMed 20202923Blekher T, Ramchandani VA, Flury L, Foroud T, Kareken D, Yee RD, Li TK, O'Connor S. Saccadic eye movements are associated with a family history of alcoholism at baseline and after exposure to alcohol. Alcohol Clin Exp Res. 2002 Oct;26(10):1568-73. doi: 10.1097/01.ALC.0000033121.05006.EF.
PubMed 12394291
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetics of the Acute Response to Alcohol in Humans
- ClinicalTrials.gov ID
- NCT01375556
- Acronym / sponsor ID
- 110180
- Conditions
- Alcoholism, Genetics
- Keywords
- Alcohol Clamp, Pharmacogenetics, Family History of Alcoholism, Pharmacodynamics, Healthy Volunteer, HV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 33 participants (actual)
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)US National Institutes of Health
- Study start
- 26 May 2011
- Primary completion
- 20 Jan 2016 (actual)
- Study completion
- 20 Jan 2016 (actual)
- First posted
- 17 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
Who may qualify
- Ages
- 21 to 30 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Male and female participants between 21-30 years of age.
- Good health as determined by medical history, physical exam, EKG and lab tests.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ethanol | Drug | – |
Primary outcome
Initial response to alcohol and adaptive response to alcohol measures for subjective ratings of alcohol effects, psychomotor performance, behavioral disinhibition tasks and autonomic measures
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2019.
- Background: PubMed 12615092Bernstein DP, Stein JA, Newcomb MD, Walker E, Pogge D, Ahluvalia T, Stokes J, Handelsman L, Medrano M, Desmond D, Zule W. Development and validation of a brief screening version of the Childhood Trauma Questionnaire. Child Abuse Negl. 2003 Feb;27(2):169-90. doi: 10.1016/s0145-2134(02)00541-0.
- Background: PubMed 20202923Bierut LJ, Agrawal A, Bucholz KK, Doheny KF, Laurie C, Pugh E, Fisher S, Fox L, Howells W, Bertelsen S, Hinrichs AL, Almasy L, Breslau N, Culverhouse RC, Dick DM, Edenberg HJ, Foroud T, Grucza RA, Hatsukami D, Hesselbrock V, Johnson EO, Kramer J, Krueger RF, Kuperman S, Lynskey M, Mann K, Neuman RJ, Nothen MM, Nurnberger JI Jr, Porjesz B, Ridinger M, Saccone NL, Saccone SF, Schuckit MA, Tischfield JA, Wang JC, Rietschel M, Goate AM, Rice JP; Gene, Environment Association Studies Consortium. A genome-wide association study of alcohol dependence. Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5082-7. doi: 10.1073/pnas.0911109107. Epub 2010 Mar 2.
- Background: PubMed 12394291Blekher T, Ramchandani VA, Flury L, Foroud T, Kareken D, Yee RD, Li TK, O'Connor S. Saccadic eye movements are associated with a family history of alcoholism at baseline and after exposure to alcohol. Alcohol Clin Exp Res. 2002 Oct;26(10):1568-73. doi: 10.1097/01.ALC.0000033121.05006.EF.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vijay A Ramchandani, Ph.D. principal investigator
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ethanol in people with Alcoholism and Genetics, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Initial response to alcohol and adaptive response to alcohol measures for subjective ratings of alcohol effects, psychomotor performance, behavioral disinhibition tasks and autonomic measures. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01375556, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2019.