AlcoholismNCT00011752
Serotonin in Alcoholism
An observational study of Alcoholism and Healthy, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Alcoholism, Healthy
- What is being tested?
- FCWAY
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2001to Sep 2005
- 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 Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Patients who have met standard DSM-IV R criteria for alcohol dependence and limited number psychiatric conditions that characterize patients with mood disorders that are difficult to separate from their alcohol use.
- Age and sex matched healthy research comparison participants. The healthy research comparison participants need to be free of medical, neurological, and psychiatric illness. They should be medication free at the time of study. They should not meet criteria for alcohol or substance abuse, and cannot have a history of such use placing them in questionable diagnostic categories.
- The age range of study participants is from 18 to 65 years.
- Subjects from a diverse racial, ethnic, and gender backgrounds will be included in the study. This is because alcohol dependence manifests itself differently in different racial and gender groups.
Who cannot join
- Significant medical problems, e.g., active GI bleed, cancer, active hepatitis B infection or other medical diseases associated with liver pathology other than hepatitis C or alcoholism (e.g. Hemochromatosis).
- Other psychiatric illnesses represent diagnostic categories not eligible for this study. Examples of these include Major Depressive Disorder, Bipolar Disorder, acute or chronic psychotic illness (e.g. Schizophrenia), and Substance Induced Mood Disorders (i.e. secondary to illicit drug dependence; e.g. heroin, cocaine, crack, PCP, and other illicit substances that affect brain function).
- Intravenous drug use within the past three months.
- Drug or medication use, strongly associated with liver dysfunction, CNS effects, or impaired GI absorption (e.g. high doses of acetaminophen, neuroleptic medications, and narcotic medications).
- History of significant GI surgery (e.g. Roux en Y procedure, partial gastrectomy), which would interfere with normal GI absorption of dietary constituents.
- Coagulation defects or lack of dual circulation.
Show all 13Show fewer
- Severe iron deficiency anemia, marked low hematocrit or hemoglobin.
- Pregnancy: a positive pregnancy test will preclude further participation in this protocol.
- Inability to give a clinical history or informed consent.
- Positive human immunodeficiency virus (HIV) diagnosis: patients with positive HIV status/AIDS will be excluded form the study.
- Individuals may be excluded from entering the study at the discretion of the Principal Investigator, Dr. Williams, based on his clinical judgment.
- Participants who have had an adverse reaction that mimics any of the anticipated adverse events in response to a pharmacological challenge study or to a prescribed medication.
- Cranial mass.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Bethesda, Maryland, 20892
About this study
Official title: Effects of Acute Plasma Tryptophan Depletion on Serotonin Receptor Occupancy and Binding Affinity Using PET in Healthy and Alcoholic Human Subjects
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.
Read more
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.
Read the 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:
- 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);
- Whether putative differences in 5-HT turnover are governed primarily by genetic variation in the 5-HT transporter (5-HTT) in alcoholics;
- Whether 5-HTT genetic variation correlates with [(18) F]-FCWAY/5-HT(1A), binding, and cerebrospinal fluid (CSF) 5-Hydroxyindoleacetic acid (5-HIAA) concentration, before and after ATD; and,
- 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 [(18)F]-FCWAY, a 5-HT (1A)-receptor antagonist. rCBF will be measured with [(15)O]-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).
- Conditions
- Alcoholism, Healthy
- Being tested
- FCWAY
- Keywords
- Serotonin Reuptake, Large Neutral Amino Acids, 5-Hydroxyindoleacetic Acid, Alcoholism, PET, TRP, Tryptophan Depletion, Healthy Volunteer
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FCWAYDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2001 (estimated)
- Study startFeb 2001
- Study completionSep 2005
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
- Observational
- Enrolment
- 75 participants
Sponsor and investigators
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00011752
- Sponsor's protocol ID
- 010090
- Other IDs
- 01-AA-0090
- Status last verified
- Sep 2005
- First submitted
- 28 Feb 2001
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Fletcher A, Bill DJ, Bill SJ, Cliffe IA, Dover GM, Forster EA, Haskins JT, Jones D, Mansell HL, Reilly Y. WAY100135: a novel, selective antagonist at presynaptic and postsynaptic 5-HT1A receptors. Eur J Pharmacol. 1993 Jun 24;237(2-3):283-91. doi: 10.1016/0014-2999(93)90280-u.
PubMed 8365456Badawy AA. Tryptophan metabolism in alcoholism. Adv Exp Med Biol. 1999;467:265-74. doi: 10.1007/978-1-4615-4709-9_33.
PubMed 10721064Nishizawa S, Benkelfat C, Young SN, Leyton M, Mzengeza S, de Montigny C, Blier P, Diksic M. Differences between males and females in rates of serotonin synthesis in human brain. Proc Natl Acad Sci U S A. 1997 May 13;94(10):5308-13. doi: 10.1073/pnas.94.10.5308.
PubMed 9144233
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Acute Plasma Tryptophan Depletion on Serotonin Receptor Occupancy and Binding Affinity Using PET in Healthy and Alcoholic Human Subjects
- ClinicalTrials.gov ID
- NCT00011752
- Acronym / sponsor ID
- 010090
- Conditions
- Alcoholism, Healthy
- Keywords
- Serotonin Reuptake, Large Neutral Amino Acids, 5-Hydroxyindoleacetic Acid, Alcoholism, PET, TRP, Tryptophan Depletion, Healthy Volunteer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 75 participants
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)US National Institutes of Health
- Study start
- Feb 2001
- Study completion
- Sep 2005
- First posted
- 1 Mar 2001 (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 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.
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:
- 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);
- Whether putative differences in 5-HT turnover are governed primarily by genetic variation in the 5-HT transporter (5-HTT) in alcoholics;
- Whether 5-HTT genetic variation correlates with [(18) F]-FCWAY/5-HT(1A), binding, and cerebrospinal fluid (CSF) 5-Hydroxyindoleacetic acid (5-HIAA) concentration, before and after ATD; and,
- 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 [(18)F]-FCWAY, a 5-HT (1A)-receptor antagonist. rCBF will be measured with [(15)O]-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 design
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Patients who have met standard DSM-IV R criteria for alcohol dependence and limited number psychiatric conditions that characterize patients with mood disorders that are difficult to separate from their alcohol use.
- Age and sex matched healthy research comparison participants. The healthy research comparison participants need to be free of medical, neurological, and psychiatric illness. They should be medication free at the time of study. They should not meet criteria for alcohol or substance abuse, and cannot have a history of such use placing them in questionable diagnostic categories.
- The age range of study participants is from 18 to 65 years.
- Subjects from a diverse racial, ethnic, and gender backgrounds will be included in the study. This is because alcohol dependence manifests itself differently in different racial and gender groups.
Key exclusion criteria (13 listed)
- Significant medical problems, e.g., active GI bleed, cancer, active hepatitis B infection or other medical diseases associated with liver pathology other than hepatitis C or alcoholism (e.g. Hemochromatosis).
- Other psychiatric illnesses represent diagnostic categories not eligible for this study. Examples of these include Major Depressive Disorder, Bipolar Disorder, acute or chronic psychotic illness (e.g. Schizophrenia), and Substance Induced Mood Disorders (i.e. secondary to illicit drug dependence; e.g. heroin, cocaine, crack, PCP, and other illicit substances that affect brain function).
- Intravenous drug use within the past three months.
- Drug or medication use, strongly associated with liver dysfunction, CNS effects, or impaired GI absorption (e.g. high doses of acetaminophen, neuroleptic medications, and narcotic medications).
- History of significant GI surgery (e.g. Roux en Y procedure, partial gastrectomy), which would interfere with normal GI absorption of dietary constituents.
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 |
|---|---|---|
| FCWAY | Drug | – |
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 4 Mar 2008.
- Background: PubMed 8365456Fletcher A, Bill DJ, Bill SJ, Cliffe IA, Dover GM, Forster EA, Haskins JT, Jones D, Mansell HL, Reilly Y. WAY100135: a novel, selective antagonist at presynaptic and postsynaptic 5-HT1A receptors. Eur J Pharmacol. 1993 Jun 24;237(2-3):283-91. doi: 10.1016/0014-2999(93)90280-u.
- Background: PubMed 10721064Badawy AA. Tryptophan metabolism in alcoholism. Adv Exp Med Biol. 1999;467:265-74. doi: 10.1007/978-1-4615-4709-9_33.
- Background: PubMed 9144233Nishizawa S, Benkelfat C, Young SN, Leyton M, Mzengeza S, de Montigny C, Blier P, Diksic M. Differences between males and females in rates of serotonin synthesis in human brain. Proc Natl Acad Sci U S A. 1997 May 13;94(10):5308-13. doi: 10.1073/pnas.94.10.5308.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Alcoholism and 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 4 inclusion and 13 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 4 Mar 2008. 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 NCT00011752, 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 4 Mar 2008.