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Trial record 9 of 39 for:    FLUMAZENIL

Characterization of [11C]Flumazenil to Image GABA Transmission in Healthy Adult Subjects and Subjects With Alcohol Dependence

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01904487
Recruitment Status : Completed
First Posted : July 22, 2013
Last Update Posted : August 29, 2017
Sponsor:
Information provided by (Responsible Party):
Rajesh Narendran, University of Pittsburgh

Brief 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.


Condition or disease Intervention/treatment Phase
Alcoholism Radiation: [11C]flumazenil Drug: Tiagabine Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Characterization of [11C]Flumazenil to Image GABA Transmission in Healthy Adult Subjects and Subjects With Alcohol Dependence
Study Start Date : April 19, 2011
Actual Primary Completion Date : October 1, 2013
Actual Study Completion Date : October 1, 2013

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PET scans
Both alcoholics and healthy controls will undergo two [11C]flumazenil PET scans: one at baseline and one post administration of 0.2 mg/kg Tiagabine.
Radiation: [11C]flumazenil
[11C]flumazenil is a radiotracer used to measure levels of the neurotransmitter GABA in the human brain.

Drug: Tiagabine
Tiagabine raises levels of GABA in the brain. It is used in this study so that we can measure the changes in GABA levels.




Primary Outcome Measures :
  1. To measure changes in [11C]flumazenil binding in the brain using PET scans [ Time Frame: Day 1: baseline PET scan and a follow-up PET scan 0.5 hours post administration of Tiagabine ]
  2. Tiagabine induced change in [C-11]flumazenil distribution volume (VT) [ Time Frame: 1 hour ]
    Refer to for consensus nomenclature J Cereb Blood Flow Metab. 2007 Sep;27(9):1533-9. Epub 2007 May 9.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01904487


Locations
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United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Rajesh Narendran
Investigators
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Principal Investigator: Rajesh Narendran, MD University of Pittsburgh

Additional Information:
Publications:
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Responsible Party: Rajesh Narendran, MD, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01904487     History of Changes
Other Study ID Numbers: PRO#10100519
First Posted: July 22, 2013    Key Record Dates
Last Update Posted: August 29, 2017
Last Verified: August 2017

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Flumazenil
Alcoholism
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Tiagabine
Antidotes
Protective Agents
Physiological Effects of Drugs
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anticonvulsants
GABA Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators