HealthyNCT00074360
The Effect of Ethanol on Brain Activity
An observational study of Healthy, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.
Trial summary
This study is divided into two parts; each designed to answer a separate but related question: Which brain regions are activated in humans by the rewarding properties of ethanol administration? Is it possible to demonstrate a conditioned response to a stimulus paired with rising blood alcohol concentrations (BAC) in… Read more about this study
- Who is it for?
- Ages 21 to 45 years
- Conditions the study is for
- Healthy
- How many people
- 107 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Dec 2003to 17 Dec 2012
- Phase
- Observational
- 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 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- in good health.
- between 21 and 45 years of age.
- <TAB>
- Currently consuming between 1 and 14 drinks per week.
- in good health.
- between 21 and 45 years of age.
Show all 10Show fewer
- currently consuming between 20 and 40 drinks per week.
- not regularly abstinent for more than 3 days per week, but have abstained from alcohol for 3 consecutive days without experiencing withdrawal symptoms.
- able to provide a plausible history that they can abstain from alcohol without significant withdrawal symptoms when coming to the clinic. In addition, each participant will be asked to quantify their worst withdrawal symptoms using the Clinical Institute Withdrawal Assessment (CIWA) Instrument. Participants who score 8 or above will not be enrolled in the protocol.
- not seeking treatment for their alcohol consumption.
Who cannot join
- have an abnormal physical exam and/or have laboratory values outside of normal ranges;
- have fulfilled DSM-IV criteria for ethanol or other substance dependency (excluding nicotine) at any time;
- have fulfilled DSM-IV criteria for a current or past major psychiatric disorder (DSM-IV Axis I) or who have ever had a head injury requiring hospitalization.
- are over or under 20% of ideal body weight;
- have taken any prescribed, non-prescribed, or over-the-counter medications or drugs within 14 days prior to the study days (excluding oral contraceptive agents);
- are pregnant;
Show all 22Show fewer
- report to have a "facial flushing" response to the consumption of ethanol;
- have never consumed at least two standard drinks of ethanol within one hour.
- have ferromagnetic objects in their bodies, which might be adversely affected by MRI (e.g., surgical clips, metal fragments in or near brain, eye or blood vessels, cardiac or neurological pacemaker, cochlear or eye implant). Any doubt about presence of these objects will result in exclusion from this study.
- Additionally, subjects will be asked to abstain from ethanol for at least 2 days prior to the studies.
- Regular tobacco users will be excluded from the study in order to avoid nicotine withdrawal symptoms. Occasional (not daily) use of tobacco products is acceptable.
- have an abnormal physical exam and/or have laboratory values outside of normal ranges;
- have fulfilled DSM-IV criteria for any substance dependency (excluding alcohol or nicotine) at any time;
- have fulfilled DSM-IV criteria for a current or past major psychiatric disorder or who have ever had a head injury requiring hospitalization.
- are over or under 20% of ideal body weight;
- have taken any prescribed, non-prescribed, or over-the-counter medications or drugs within 14 days prior to the study days (excluding oral contraceptive agents);
- are pregnant;
- report to have a "facial flushing" response to the consumption of ethanol;
- have never consumed at least two standard drinks of ethanol within one hour.
- have ferromagnetic objects in their bodies, which might be adversely affected by MRI (e.g., surgical clips, metal fragments in or near brain, eye or blood vessels, cardiac or neurological pacemaker, cochlear or eye implant). Any doubt about presence of these objects will result in exclusion from this study.
- Additionally, subjects will be asked to abstain from ethanol for at least 2 days prior to the studies.
- Regular tobacco users will be excluded from the study in order to avoid nicotine withdrawal symptoms. Occasional (not daily) use of tobacco products is acceptable.
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: The Effect of Ethanol on Cerebral Blood Flow as Measured by Functional Magnetic Resonance Imaging and the Development of Conditioned Response to Ethanol Administration
This study is divided into two parts; each designed to answer a separate but related question:
Which brain regions are activated in humans by the rewarding properties of ethanol administration?
Read more
Is it possible to demonstrate a conditioned response to a stimulus paired with rising blood alcohol concentrations (BAC) in humans and can this response be observed in the brain using functional magnetic resonance images (fMRI) techniques?
Part 1. In order to determine which brain regions are activated by the rewarding properties of ethanol administration, we propose to use Blood Oxygenation Level Dependent (BOLD) fMRI techniques to test the hypothesis that during the time of rising and peak BAC, mesolimbic, mesocortical, and nigrostriatal dopamine (DA) terminal areas of the brain will show significant increases in cerebral blood flow. Healthy, non-alcoholic subjects will be given intravenous (IV) ethanol or placebo infusions on separate days. The infusions will have three phases. On each day, during the first phase a saline infusion will be used to measure basal brain blood flow. The second phase will be an ethanol infusion delivered at rates calculated to produce a BAC of 0.08 plus or minus 0.005 g/dl at 10 minutes. The rate of the infusion for the next 10 minutes (third phase) will be calculated to maintain BAC at the target level of 0.08 plus or minus 0.005 g/dl for the duration of the infusion. On the placebo day, subjects will receive a saline infusion at the same set of rates for phases two and three as used during their ethanol infusion. Continuous multi-slice fMRI data will be collected during each infusion.
Part 2. In order to investigate conditioned response to ethanol, three groups of healthy, non-alcoholic subjects will be given a series of IV infusions on separate days. The experimental group will receive ethanol infusion paired with a conditioned stimulus (CS) which will be presented while the BAC is rising. One control group (I) of healthy, non-alcoholic subjects will also be given a series of intravenous ethanol infusions on separate days, but these infusions will not be paired with a CS. The other control group (II) will be given only saline infusions during the CS presentation. After three training sessions, all three groups will undergo an fMRI scan during which the CS will be paired with saline infusion. This will allow the response to the CS alone to be observed. After 10 minutes of CS presentation, the ethanol infusion will begin and continue for another 15 minutes. Conditioned response (CR) will be demonstrated if the experimental group shows greater increase in BOLD signal than the control groups in motivation areas such as mesolimbic, mesocortical, and nigrostriatal dopamine (DA) terminal areas of the brain in response to the CS while they receive the saline infusion. Control group II will also undergo an fMRI scan and will be given saline infusion followed by ethanol infusion during their last 15 minutes in the scanner to control for the non-specific effects of repeated infusions \& scans on BOLD response to ethanol. If we are able to produce a CR in brain regions associated with motivation, it may be possible to use this CR as an experimental model for human alcohol craving.
Read the detailed description
This study is designed to answer four questions:
- Which brain regions are activated in humans by the rewarding properties of ethanol administration?
- How does ethanol administration affect the brain response to visual cues known to evoke positive or negative emotion?
- Do individuals who regularly drink in ethanol in large amounts (heavy drinkers) differ from individuals who do not regularly drink large amounts of ethanol (social drinkers) in how ethanol affects brain function?
- Does ethanol administration affect the brain regions activated in a risk-taking task in social drinkers and heavy drinkers?
In order to determine which brain regions are activated by the rewarding properties of ethanol administration, we propose to use Blood Oxygenation Level Dependent (BOLD) fMRI techniques to test the hypothesis that during the time of rising and peak BAC, mesolimbic, mesocortical, and nigrostriatal dopamine (DA) terminal areas of the brain will show significant increases in cerebral blood flow. Healthy, subjects who are not seeking treatment for an alcohol use disorder will be given intravenous (IV) ethanol or placebo infusions on separate days. An ethanol infusion will delivered at rates calculated to produce a BAC of 0.08 plus or minus. An ethanol infusion will delivered at rates calculated to produce a BAC of 0.08 plus or minus 0.005 g/dl at 15 minutes. Then the rate of the infusion will be adjusted so that for the next 30 minutes (second phase) BAC will be maintained at the target level of 0.08 0.005 g/dl. On the placebo day, subjects will receive a saline infusion at the same set of rates as used during their ethanol infusion. Continuous multi-slice fMRI data will be collected during each infusion. During each infusion, BOLD response to visual stimuli designed to evoke emotion will also be examined. In addition, we will compare the BOLD response of healthy social drinkers to that of healthy heavy drinkers. We will also compare the BOLD response elicited by risk-taking during the ethanol infusion to that during the placebo infusion in both social and heavy drinkers.
- Conditions
- Healthy
- Keywords
- Ethanol, fMRI, Blood Flow, Conditioning, Reinforcement
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2003 (estimated)
- Study start9 Dec 2003
- Study completion17 Dec 2012
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 HealthyStudies 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
- Observational
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Sponsor type
- US National Institutes of Health
- Investigators
- Daniel W Hommer, M.D., Principal investigator, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00074360
- Sponsor's protocol ID
- 040060
- Other IDs
- 04-AA-0060
- Status last verified
- 17 Dec 2012
- First submitted
- 10 Dec 2003
- Last updated
- 16 Dec 2019
- Results posted
- No
Publications
Blekher 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 12394291Boileau I, Assaad JM, Pihl RO, Benkelfat C, Leyton M, Diksic M, Tremblay RE, Dagher A. Alcohol promotes dopamine release in the human nucleus accumbens. Synapse. 2003 Sep 15;49(4):226-31. doi: 10.1002/syn.10226.
PubMed 12827641Breiter HC, Gollub RL, Weisskoff RM, Kennedy DN, Makris N, Berke JD, Goodman JM, Kantor HL, Gastfriend DR, Riorden JP, Mathew RT, Rosen BR, Hyman SE. Acute effects of cocaine on human brain activity and emotion. Neuron. 1997 Sep;19(3):591-611. doi: 10.1016/s0896-6273(00)80374-8.
PubMed 9331351
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Ethanol on Cerebral Blood Flow as Measured by Functional Magnetic Resonance Imaging and the Development of Conditioned Response to Ethanol Administration
- ClinicalTrials.gov ID
- NCT00074360
- Acronym / sponsor ID
- 040060
- Conditions
- Healthy
- Keywords
- Ethanol, fMRI, Blood Flow, Conditioning, Reinforcement
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 107 participants (actual)
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)US National Institutes of Health
- Study start
- 9 Dec 2003
- Study completion
- 17 Dec 2012
- First posted
- 11 Dec 2003 (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.
This study is divided into two parts; each designed to answer a separate but related question:
Which brain regions are activated in humans by the rewarding properties of ethanol administration?
Is it possible to demonstrate a conditioned response to a stimulus paired with rising blood alcohol concentrations (BAC) in humans and can this response be observed in the brain using functional magnetic resonance images (fMRI) techniques?
Part 1. In order to determine which brain regions are activated by the rewarding properties of ethanol administration, we propose to use Blood Oxygenation Level Dependent (BOLD) fMRI techniques to test the hypothesis that during the time of rising and peak BAC, mesolimbic, mesocortical, and nigrostriatal dopamine (DA) terminal areas of the brain will show significant increases in cerebral blood flow. Healthy, non-alcoholic subjects will be given intravenous (IV) ethanol or placebo infusions on separate days. The infusions will have three phases. On each day, during the first phase a saline infusion will be used to measure basal brain blood flow. The second phase will be an ethanol infusion delivered at rates calculated to produce a BAC of 0.08 plus or minus 0.005 g/dl at 10 minutes. The rate of the infusion for the next 10 minutes (third phase) will be calculated to maintain BAC at the target level of 0.08 plus or minus 0.005 g/dl for the duration of the infusion. On the placebo day, subjects will receive a saline infusion at the same set of rates for phases two and three as used during their ethanol infusion. Continuous multi-slice fMRI data will be collected during each infusion.
Part 2. In order to investigate conditioned response to ethanol, three groups of healthy, non-alcoholic subjects will be given a series of IV infusions on separate days. The experimental group will receive ethanol infusion paired with a conditioned stimulus (CS) which will be presented while the BAC is rising. One control group (I) of healthy, non-alcoholic subjects will also be given a series of intravenous ethanol infusions on separate days, but these infusions will not be paired with a CS. The other control group (II) will be given only saline infusions during the CS presentation. After three training sessions, all three groups will undergo an fMRI scan during which the CS will be paired with saline infusion. This will allow the response to the CS alone to be observed. After 10 minutes of CS presentation, the ethanol infusion will begin and continue for another 15 minutes. Conditioned response (CR) will be demonstrated if the experimental group shows greater increase in BOLD signal than the control groups in motivation areas such as mesolimbic, mesocortical, and nigrostriatal dopamine (DA) terminal areas of the brain in response to the CS while they receive the saline infusion. Control group II will also undergo an fMRI scan and will be given saline infusion followed by ethanol infusion during their last 15 minutes in the scanner to control for the non-specific effects of repeated infusions \& scans on BOLD response to ethanol. If we are able to produce a CR in brain regions associated with motivation, it may be possible to use this CR as an experimental model for human alcohol craving.
Detailed description
This study is designed to answer four questions:
- Which brain regions are activated in humans by the rewarding properties of ethanol administration?
- How does ethanol administration affect the brain response to visual cues known to evoke positive or negative emotion?
- Do individuals who regularly drink in ethanol in large amounts (heavy drinkers) differ from individuals who do not regularly drink large amounts of ethanol (social drinkers) in how ethanol affects brain function?
- Does ethanol administration affect the brain regions activated in a risk-taking task in social drinkers and heavy drinkers?
In order to determine which brain regions are activated by the rewarding properties of ethanol administration, we propose to use Blood Oxygenation Level Dependent (BOLD) fMRI techniques to test the hypothesis that during the time of rising and peak BAC, mesolimbic, mesocortical, and nigrostriatal dopamine (DA) terminal areas of the brain will show significant increases in cerebral blood flow. Healthy, subjects who are not seeking treatment for an alcohol use disorder will be given intravenous (IV) ethanol or placebo infusions on separate days. An ethanol infusion will delivered at rates calculated to produce a BAC of 0.08 plus or minus. An ethanol infusion will delivered at rates calculated to produce a BAC of 0.08 plus or minus 0.005 g/dl at 15 minutes. Then the rate of the infusion will be adjusted so that for the next 30 minutes (second phase) BAC will be maintained at the target level of 0.08 0.005 g/dl. On the placebo day, subjects will receive a saline infusion at the same set of rates as used during their ethanol infusion. Continuous multi-slice fMRI data will be collected during each infusion. During each infusion, BOLD response to visual stimuli designed to evoke emotion will also be examined. In addition, we will compare the BOLD response of healthy social drinkers to that of healthy heavy drinkers. We will also compare the BOLD response elicited by risk-taking during the ethanol infusion to that during the placebo infusion in both social and heavy drinkers.
Study design
Who may qualify
- Ages
- 21 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- <TAB>
- in good health.
- between 21 and 45 years of age.
- currently consuming between 20 and 40 drinks per week.
- not regularly abstinent for more than 3 days per week, but have abstained from alcohol for 3 consecutive days without experiencing withdrawal symptoms.
Key exclusion criteria (22 listed)
- have an abnormal physical exam and/or have laboratory values outside of normal ranges;
- have fulfilled DSM-IV criteria for ethanol or other substance dependency (excluding nicotine) at any time;
- have fulfilled DSM-IV criteria for a current or past major psychiatric disorder (DSM-IV Axis I) or who have ever had a head injury requiring hospitalization.
- are over or under 20% of ideal body weight;
- have taken any prescribed, non-prescribed, or over-the-counter medications or drugs within 14 days prior to the study days (excluding oral contraceptive agents);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2019.
- 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.
- Background: PubMed 12827641Boileau I, Assaad JM, Pihl RO, Benkelfat C, Leyton M, Diksic M, Tremblay RE, Dagher A. Alcohol promotes dopamine release in the human nucleus accumbens. Synapse. 2003 Sep 15;49(4):226-31. doi: 10.1002/syn.10226.
- Background: PubMed 9331351Breiter HC, Gollub RL, Weisskoff RM, Kennedy DN, Makris N, Berke JD, Goodman JM, Kantor HL, Gastfriend DR, Riorden JP, Mathew RT, Rosen BR, Hyman SE. Acute effects of cocaine on human brain activity and emotion. Neuron. 1997 Sep;19(3):591-611. doi: 10.1016/s0896-6273(00)80374-8.
Related trials for Healthy
Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
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.
Daniel W Hommer, M.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?
An observational study of Healthy, 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 10 inclusion and 22 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: finished, as of the sponsor's last update on 16 Dec 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00074360, 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 16 Dec 2019.