Ignite Creation Date:
2024-05-05 @ 11:32 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00074360
Status:
COMPLETED
Last Update Posted:
2019-12-16
First Post:
2003-12-10
Brief Title:
The Effect of Ethanol on Brain Activity
Sponsor:
National Institute on Alcohol Abuse and Alcoholism NIAAA
Organization:
National Institutes of Health Clinical Center CC
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2012-12-17
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 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 008 plus or minus 0005 gdl 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 008 plus or minus 0005 gdl 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
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 008 plus or minus 0005 gdl 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 008 plus or minus 0005 gdl 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
1 Which brain regions are activated in humans by the rewarding properties of ethanol administration
2 How does ethanol administration affect the brain response to visual cues known to evoke positive or negative emotion
3 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
4 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 008 plus or minus An ethanol infusion will delivered at rates calculated to produce a BAC of 008 plus or minus 0005 gdl 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 008 0005 gdl 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
1 Which brain regions are activated in humans by the rewarding properties of ethanol administration
2 How does ethanol administration affect the brain response to visual cues known to evoke positive or negative emotion
3 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
4 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 008 plus or minus An ethanol infusion will delivered at rates calculated to produce a BAC of 008 plus or minus 0005 gdl 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 008 0005 gdl 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 04-AA-0060 | None | None | None |