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

NCT01904487 | Completed Phase 1 FDA Drug

• 1 other identifier: PRO#10100519
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Alcoholism

Outcome Measures

Primary Outcomes (2)

• To measure changes in [11C]flumazenil binding in the brain using PET scans

  Day 1: baseline PET scan and a follow-up PET scan 0.5 hours post administration of Tiagabine

• Tiagabine induced change in [C-11]flumazenil distribution volume (VT)

  Refer to for consensus nomenclature J Cereb Blood Flow Metab. 2007 Sep;27(9):1533-9. Epub 2007 May 9.

  1 hour

Study Arms (1)

PET scans

EXPERIMENTAL

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; Drug: Tiagabine

Interventions

[11C]flumazenil RADIATION

\[11C\]flumazenil is a radiotracer used to measure levels of the neurotransmitter GABA in the human brain.

PET scans

Tiagabine DRUG

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

PET scans

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy Control Subjects:
• Males or Females 18-45
• Absence of present or past psychiatric conditions (including alcohol or drug dependence)
• A negative urine drug screen
• Medically Healthy
• Subjects with alcohol dependence:
• Males or Females 18-45
• Fulfill DSM-IV Diagnosis for Alcohol Dependence
• Negative Urine Drug Screen
• Negative Urine ETG/ETS
• Medically Healthy
• Abstinent from alcohol for a minimum of 1 month prior to scanning procedures

You may not qualify if:

• Healthy Control Subjects:
• Pregnancy or lactation, lack of effective birth control during 15 days before the scans
• Presence or positive history of serious medical or neurological illness, including low hemoglobin.
• Any use (within recent past 6 weeks) of amphetamines, opiates, cocaine, ecstasy PCP.
• 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.
• 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).
• 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:
• Pregnancy or lactation, lack of effective birth control during 15 days before the scans
• Presence or positive history of serious medical or neurological illness or any cardiovascular disease, low hemoglobin
• Any other current major axis I psychiatric diagnosis except alcohol dependence (subjects with nicotine dependence will not be excluded)
• 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.
• 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).
• 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)

Sponsors & Collaborators

• Rajesh Narendran: lead

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (4)

• 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. doi: 10.1007/s00213-005-2271-x. Epub 2005 Apr 28.

  PMID: 15864554 BACKGROUND

• 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. doi: 10.1111/j.1530-0277.1996.tb01149.x.

  PMID: 8947325 BACKGROUND

• 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. doi: 10.1007/978-3-0348-7330-7_15.

  PMID: 8032146 BACKGROUND

• 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. doi: 10.1016/0925-4927(93)90019-e.

  PMID: 8390063 BACKGROUND

Related Links

• Psychiatric Molecular Imaging Program Addiction Website

MeSH Terms

Conditions

Alcoholism

Interventions

Tiagabine

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Nipecotic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Piperidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Rajesh Narendran, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: July 16, 2013
• First Posted: July 22, 2013
• Study Start: April 19, 2011
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: August 29, 2017

Record last verified: 2017-08

Locations

US (1)