Characterization of [11C]Flumazenil to Image GABA Transmission in Healthy Adult Subjects and Subjects With Alcohol Dependence
Information source: University of Pittsburgh
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Alcoholism
Intervention: [11C]flumazenil (Radiation); Tiagabine (Drug)
Phase: Phase 1
Status: Terminated
Sponsored by: Rajesh Narendran Official(s) and/or principal investigator(s): Rajesh Narendran, MD, Principal Investigator, Affiliation: University of Pittsburgh
Summary
Background:
- This study is being done to examine the role of a chemical GABA in the brain of alcohol
dependent patients. GABA is the chief inhibitory neurotransmitter in the central nervous
system. It helps induce relaxation and sleep and balances the brain by inhibiting
over-excitation. Several studies have reported that anxiety disorders such as panic
attacks, seizure disorders, and numerous other conditions including addiction, are all
related to low GABA activity. Therefore, we will examine differences in GABA levels between
healthy controls and subjects with alcohol addiction. Studies such as this are important to
the understanding of the role of GABA in alcohol addiction.
Clinical Details
Official title: Characterization of [11C]Flumazenil to Image GABA Transmission in Healthy Adult Subjects and Subjects With Alcohol Dependence
Study design: Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science
Primary outcome: To measure changes in [11C]flumazenil binding in the brain using PET scans
Detailed description:
Objectives:
- By comparing the two PET scans (before and after tiagabine) done in the same day, we can
understand more about how much GABA your brain makes and about the activity of your GABA
receptors in the brain.
Eligibility:
- Individuals 18-45 years of age who are heavy drinkers or healthy controls.
Design:
- Procedures to determine if you are eligible to take part in a research study are called
"screening procedures". This will require you to come to the investigators office for
approximately ½ day. For this research study, the screening procedures include
comprehensive psychiatric and medical evaluations. Participants be asked to abstain
from drugs and alcohol for the duration of the study and will be required to make trips
several times a week for two weeks to provide clean urine samples.
- During one of the visits prior to the PET scans, participants will have a magnetic
resonance image (MRI) taken of their brain.
- We will be using a technology called Positron Emission Tomography (PET), which is a
method used to take pictures of the body, in this case, the brain. We will be injecting
you with a radiotracer called [11C]flumazenil. A radiotracer is a small amount of a
drug with radioactivity attached. Because the radiotracer temporarily sticks to the
GABA receptors in the brain, the PET scan can then measure the activity at GABA
receptors by measuring the amount of the radiotracer. You will undergo two PET scans
with [11C]flumazenil on one day for this study. After the first PET scan, you will be
given an oral dose of tiagabine (Gabitril®), which is a medication approved for the
treatment of seizure disorder. Tiagabine raises levels of GABA in the brain. It is
used in this study so that we can measure the changes in GABA levels. Blood samples
will be drawn during the PET scans.
Eligibility
Minimum age: 18 Years.
Maximum age: 45 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
Healthy Control Subjects:
1. Males or Females 18-45
2. Absence of present or past psychiatric conditions (including alcohol or drug
dependence)
3. A negative urine drug screen
4. Medically Healthy
Subjects with alcohol dependence:
1. Males or Females 18-45
2. Fulfill DSM-IV Diagnosis for Alcohol Dependence
3. Negative Urine Drug Screen
4. Negative Urine ETG/ETS
5. Medically Healthy
6. Abstinent from alcohol for a minimum of 1 month prior to scanning procedures
Exclusion Criteria:
Healthy Control Subjects:
1. Pregnancy or lactation, lack of effective birth control during 15 days before the
scans
2. Presence or positive history of serious medical or neurological illness, including
low hemoglobin.
3. Any use (within recent past 6 weeks) of amphetamines, opiates, cocaine, ecstasy PCP.
4. Metal implants or paramagnetic objects contained within the body which may interfere
with the MRI scan (but not limited to, those with a pacemaker, presence of metallic
fragments near the eyes or spinal cord, or cochlear implant. Dental fillings do not
present a risk for MRI), as determined in consultation with a neuroradiologist and
according to the guidelines set forth in the following reference book commonly used
by neuroradiologists.
5. Currently employed as radiation worker; or participation in radioactive drug research
protocols within the previous year such that the total cumulative annual radiation
dose (i. e., from participation in the previous research studies and this study) would
exceed the radiation dose limits specified in the FDA regulations at 21 CFR 361. 1,
Radioactive Drugs Considered Generally Safe and Effective (i. e. annual cumulative
radiation dose limit = 5 rems to gonads, blood-forming organs, lens of eye, whole
body; 15 rems to other organs).
6. Subjects with known hypersensitivity to flumazenil or benzodiazepines; subjects who
have been given a benzodiazepine for control of a potentially life-threatening
condition (e. g., control of intracranial pressure or status epilepticus or in patient
who are showing signs of serious cyclic antidepressant overdose)
Subjects with alcohol dependence:
1. Pregnancy or lactation, lack of effective birth control during 15 days before the
scans
2. Presence or positive history of serious medical or neurological illness or any
cardiovascular disease, low hemoglobin
3. Any other current major axis I psychiatric diagnosis except alcohol dependence
(subjects with nicotine dependence will not be excluded)
4. Metal implants or paramagnetic objects contained within the body which may interfere
with the MRI scan (but not limited to, those with a pacemaker, presence of metallic
fragments near the eyes or spinal cord, or cochlear implant. Dental fillings do not
present a risk for MRI), as determined in consultation with a neuroradiologist and
according to the guidelines set forth in the following reference book commonly used
by neuroradiologists.
5. Currently employed as radiation worker; or participation in radioactive drug research
protocols within the previous year such that the total cumulative annual radiation
dose (i. e., from participation in the previous research studies and this study) would
exceed the radiation dose limits specified in the FDA regulations at 21 CFR 361. 1,
Radioactive Drugs Considered Generally Safe and Effective (i. e. annual cumulative
radiation dose limit = 5 rems to gonads, blood-forming organs, lens of eye, whole
body; 15 rems to other organs).
6. Subjects with known hypersensitivity to flumazenil or benzodiazepines; subjects who
have been given a benzodiazepine for control of a potentially life-threatening
condition (e. g., control of intracranial pressure or status epilepticus or in patient
who are showing signs of serious cyclic antidepressant overdose)
Locations and Contacts
University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
Additional Information
Psychiatric Molecular Imaging Program Addiction Website
Related publications: Lingford-Hughes AR, Wilson SJ, Cunningham VJ, Feeney A, Stevenson B, Brooks DJ, Nutt DJ. GABA-benzodiazepine receptor function in alcohol dependence: a combined 11C-flumazenil PET and pharmacodynamic study. Psychopharmacology (Berl). 2005 Aug;180(4):595-606. Epub 2005 Apr 28. Gilman S, Adams KM, Johnson-Greene D, Koeppe RA, Junck L, Kluin KJ, Martorello S, Heumann M, Hill E. Effects of disulfiram on positron emission tomography and neuropsychological studies in severe chronic alcoholism. Alcohol Clin Exp Res. 1996 Nov;20(8):1456-61. Farde L, Pauli S, Litton JE, Halldin C, Neiman J, Sedvall G. PET-determination of benzodiazepine receptor binding in studies on alcoholism. EXS. 1994;71:143-53. Litton JE, Neiman J, Pauli S, Farde L, Hindmarsh T, Halldin C, Sedvall G. PET analysis of [11C]flumazenil binding to benzodiazepine receptors in chronic alcohol-dependent men and healthy controls. Psychiatry Res. 1993 Apr;50(1):1-13.
Starting date: April 2011
Last updated: January 27, 2014
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