Ignite Creation Date:
2024-05-05 @ 11:23 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00011752
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
2001-02-28
Brief Title:
Serotonin in Alcoholism
Sponsor:
National Institute on Alcohol Abuse and Alcoholism NIAAA
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Effects of Acute Plasma Tryptophan Depletion on Serotonin Receptor Occupancy and Binding Affinity Using PET in Healthy and Alcoholic Human Subjects
Status:
COMPLETED
Status Verified Date:
2005-09
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 uses positron emission tomography PET scanning to study how serotonin works in alcoholics Serotonin is a chemical that allows brain cells to communicate There is evidence that people with alcoholism have altered serotonin their brains begin to make and break down serotonin more slowly than people who do not drink PET scans use radioactive substances injected into the body A special camera detects the radiation emitted by the radioactive fluid and a computer processes the radioactivity into images of the brain which show the activity of brain chemicals like serotonin
People with alcohol dependency may participate in this study Candidates are screened with a medical history including questions about alcohol and drug use physical examination blood tests breath alcohol tests electrocardiogram ECG urine test for illicit drugs and for women a pregnancy test and a stool test for hidden blood They also undergo magnetic resonance imaging MRI scan of the brain and complete questionnaires on their alcohol and drug history
Participants undergo the following tests and procedures
Diet low in tryptophan Tryptophan is an amino acid from which serotonin is made
Brain MRI before starting the study to make sure brain structure is normal
Lumbar puncture spinal tap to collect a small sample of cerebrospinal fluid CSF A local anesthetic is given and a needle is inserted in the space between the bones vertebrae in the lower back About 2 tablespoons of fluid is collected through the needle
Arterial catheter plastic tube placed in an artery in the wrist area for drawing blood samples The skin is numbed with a local anesthetic for placement of the catheter
Intravenous IV catheter placed in a vein for injecting the radioactive isotope used in the PET scan
Two PET scans - baseline and active
Amino acid drink orange flavored before the active PET scan The drink lowers tryptophan levels
Amino acid capsules - 23 amino acid capsules are taken with the orange drink
Genetic analysis to help understand serotonin and alcoholism A blood sample is collected for DNA testing and possibly establishment of a cell line collection of cells that are grown in the laboratory from an original tissue specimen for other genetic studies
Patients are admitted to the intensive care unit for the lumbar puncture and arterial line procedures After these procedures are complete the patient is transferred by stretcher to the PET suite for scanning During the two scans blood samples are drawn from the artery and a small amount of CSF is collected each hour of the study Each PET scanning session lasts about 3 hours The study lasts 36 hours during which time the subject remains in bed
People with alcohol dependency may participate in this study Candidates are screened with a medical history including questions about alcohol and drug use physical examination blood tests breath alcohol tests electrocardiogram ECG urine test for illicit drugs and for women a pregnancy test and a stool test for hidden blood They also undergo magnetic resonance imaging MRI scan of the brain and complete questionnaires on their alcohol and drug history
Participants undergo the following tests and procedures
Diet low in tryptophan Tryptophan is an amino acid from which serotonin is made
Brain MRI before starting the study to make sure brain structure is normal
Lumbar puncture spinal tap to collect a small sample of cerebrospinal fluid CSF A local anesthetic is given and a needle is inserted in the space between the bones vertebrae in the lower back About 2 tablespoons of fluid is collected through the needle
Arterial catheter plastic tube placed in an artery in the wrist area for drawing blood samples The skin is numbed with a local anesthetic for placement of the catheter
Intravenous IV catheter placed in a vein for injecting the radioactive isotope used in the PET scan
Two PET scans - baseline and active
Amino acid drink orange flavored before the active PET scan The drink lowers tryptophan levels
Amino acid capsules - 23 amino acid capsules are taken with the orange drink
Genetic analysis to help understand serotonin and alcoholism A blood sample is collected for DNA testing and possibly establishment of a cell line collection of cells that are grown in the laboratory from an original tissue specimen for other genetic studies
Patients are admitted to the intensive care unit for the lumbar puncture and arterial line procedures After these procedures are complete the patient is transferred by stretcher to the PET suite for scanning During the two scans blood samples are drawn from the artery and a small amount of CSF is collected each hour of the study Each PET scanning session lasts about 3 hours The study lasts 36 hours during which time the subject remains in bed
Detailed Description:
This research concerns the study of serotonin 5-HT synthesis metabolism turnover and release We hypothesize that neuronal 5-HT turnover and release is altered in alcoholic individuals and that this plays a role in alcohol seeking behavior We wish to determine the following
1 Whether there are differences in 5-HT turnover and release in alcoholics compared to healthy research comparison participants before and after Acute Tryptophan Depletion ATD
2 Whether putative differences in 5-HT turnover are governed primarily by genetic variation in the 5-HT transporter 5-HTT in alcoholics
3 Whether 5-HTT genetic variation correlates with 18 F-FCWAY5-HT1A binding and cerebrospinal fluid CSF 5-Hydroxyindoleacetic acid 5-HIAA concentration before and after ATD and
4 If regional cerebral blood flow rCBF differs at baseline and after ATD in alcoholics and healthy research comparison participants
To investigate the underlying biochemistry of 5-HT neurometabolism we will use two experimental strategies Acute Tryptophan TRP Depletion ATD and positron emission tomography PET imaging to investigate 5-HT neurochemistry We will deplete plasma TRP using ATD while simultaneously collecting CSF 5-HIAA and performing intermittent plasma sampling via indwelling catheters TRP is the amino acid AA precursor needed for 5-HT synthesis 5-HIAA is the principal metabolite of 5-HT It is a neurochemical marker of neuronal 5-HT metabolism PET will allow indirect measurements of synaptic 5-HT concentration by measuring binding of 18F-FCWAY a 5-HT 1A-receptor antagonist rCBF will be measured with 15O-water imaging Studies will be performed before and after ATD Individuals will be genotyped for the 5-HT transporter 5-HTT Plasma TRP and Large Neutral Amino Acids LNAAs and CSF TRP and 5-HIAA concentrations will be measured using High Performance Liquid Chromatography HPLC
1 Whether there are differences in 5-HT turnover and release in alcoholics compared to healthy research comparison participants before and after Acute Tryptophan Depletion ATD
2 Whether putative differences in 5-HT turnover are governed primarily by genetic variation in the 5-HT transporter 5-HTT in alcoholics
3 Whether 5-HTT genetic variation correlates with 18 F-FCWAY5-HT1A binding and cerebrospinal fluid CSF 5-Hydroxyindoleacetic acid 5-HIAA concentration before and after ATD and
4 If regional cerebral blood flow rCBF differs at baseline and after ATD in alcoholics and healthy research comparison participants
To investigate the underlying biochemistry of 5-HT neurometabolism we will use two experimental strategies Acute Tryptophan TRP Depletion ATD and positron emission tomography PET imaging to investigate 5-HT neurochemistry We will deplete plasma TRP using ATD while simultaneously collecting CSF 5-HIAA and performing intermittent plasma sampling via indwelling catheters TRP is the amino acid AA precursor needed for 5-HT synthesis 5-HIAA is the principal metabolite of 5-HT It is a neurochemical marker of neuronal 5-HT metabolism PET will allow indirect measurements of synaptic 5-HT concentration by measuring binding of 18F-FCWAY a 5-HT 1A-receptor antagonist rCBF will be measured with 15O-water imaging Studies will be performed before and after ATD Individuals will be genotyped for the 5-HT transporter 5-HTT Plasma TRP and Large Neutral Amino Acids LNAAs and CSF TRP and 5-HIAA concentrations will be measured using High Performance Liquid Chromatography HPLC
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 |
|---|---|---|---|
| 01-AA-0090 | None | None | None |