NIH Clinical Research Studies

Protocol Number: 04-AA-0060

Active Accrual, Protocols Recruiting New Patients

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
Number:
04-AA-0060
Summary:
This two-part study will use magnetic resonance imaging (MRI) to: 1) determine which brain regions are activated when ethanol (alcohol) is given through a vein, and 2) show a conditioned brain response to a stimulus paired with rising blood alcohol concentrations. A famous example of a conditioned response is the experiment by the Russian scientist Ivan Pavlov, who conditioned dogs to respond in a predictable manner by ringing a bell before feeding them. After some time, the dogs salivated as if they were about to eat simply upon hearing the bell. Many scientists think that the intense craving for alcohol often reported by alcoholics may result from some form of conditioning.

Healthy volunteers between 21 and 45 years of age who are within 20 percent of their ideal body weight may be eligible for this study. Candidates will be screened with a medical history and physical examination, electrocardiogram, psychiatric interview, and blood and urine tests.

All study participants will undergo the following procedures:

-Ethanol tolerance testing: Participants will have an ethanol infusion in the outpatient clinic to determine their reaction to the infusion - that is, if it causes nausea or malaise, a good feeling, etc. Participants will fill out rating scales to indicate how they feel.

-Functional MRI scanning: On two separate days following the tolerance testing, participants will undergo MRI scans. For participants in part 1, these scans will be scheduled at least 1 week apart, and for participants in part 2, the scans will be done on study day 2 (following the tolerance testing) and on day 6. An initial scan will provide a picture of the physical structure of the brain. Then, scans will be done while either ethanol or placebo (saline) is infused through a vein to examine brain activity during the infusions. Participants in group 2 will be shown a variety of visual stimuli during infusion on day 6. At the end of each scan, participants will complete questionnaires to rate the effects of the infusion.

-Conditioning infusions (only for participants in part 2 of the study): Part 2 study participants who experience a pleasant feeling from the ethanol infusions and who show brain activation in response to them will be randomly assigned to one of three groups for the conditioning phase of the study. All participants will receive either placebo or ethanol infusions on study days 3, 4, and 5. In one group the ethanol infusions will be paired with a visual stimulus; in a second group the infusions will not be paired with a visual stimulus; and in a third group, subjects will be given infusions of saline instead of ethanol.

All infusions in both parts of the study have three phases. The first phase is a saline infusion, which lasts for several minutes. During the second phase, ethanol or placebo is administered for several minutes. Ethanol infusions will raise the blood alcohol concentration up to the level most people achieve after quickly drinking the equivalent of two or three standard drinks (e.g., a 12-oz beer). During the third phase, the ethanol or saline infusion is continued to maintain the blood alcohol level at the same concentration for the remainder of the infusion.

Participants will also be asked to agree to have genetic testing to determine which version they have of several different genes that are related to regulation of chemicals that affect mood, behavior, or psychiatric disorders such as alcohol dependence or depression.

Sponsoring Institute:
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Recruitment Detail
Type: Active Accrual Of New Subjects
Gender: Male & Female
Referral Letter Required: No
Population Exclusion(s): Children

Eligibility Criteria:
INCLUSION CRITERIA

Healthy volunteers will be admitted to the study after a complete medical and neuropsychiatric evaluation, including clinically indicated laboratory, radiological and EKG examinations, in accordance with the Handbook of Staff Physicians (NIH-206). A urine sample will be obtained from each subject for drug screening purposes and for pregnancy determination in females. If the drug screen is positive, the subject will not be allowed to participate further in the study, but will be paid for any participation up to that point.

EXCLUSION CRITERIA

Prospective subjects will be excluded from the study if they:

1) have an abnormal physical exam and/or have laboratory values outside of normal ranges;

2) have fulfilled DSM-IV criteria for ethanol or other substance dependency (excluding nicotine) at any time;

3) 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;

4) are not between 21 and 45 years of age;

5) are over or under 20% of ideal body weight;

6) have taken any prescribed, non-prescribed, or over-the-counter medications or drugs within 14 days prior to the study days (including oral contraceptive agents);

7) are pregnant;

8) report to have a "facial flushing" response to the consumption of ethanol;

9) have never consumed at least two servings of ethanol within one hour;

10) 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;

11) premenopausal women must be between 1 and 5 days past completion of menses at the time of the fMRI scan;

12) additionally, subjects will be asked to abstain from ethanol for at least 3 days prior to the studies;

13) participants will be required to refrain from consuming caffeine at least 4 hours before the scan. Smokers will be excluded from the study in order to avoid nicotine withdrawal symptoms.

Special Instructions: Currently Not Provided
Keywords:
Ethanol
fMRI
Blood Flow
Conditioning
Reinforcement
Recruitment Keywords:
None
Conditions:
Healthy
Investigational Drug(s):
None
Investigational Device(s):
None

Contacts:
Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:
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. PMID: 12394291

Boileau 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. PMID: 12827641

Breiter 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. PMID: 9331351

Active Accrual, Protocols Recruiting New Patients

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