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AlcoholismPhase 1NCT01904487

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

A Phase 1 study testing [11C]flumazenil and Tiagabine in people with Alcoholism, run by Rajesh Narendran at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for
Alcoholism
What is being tested?
[11C]flumazenil and Tiagabine
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
1 siteUnited States
Study dates
19 Apr 2011to 1 Oct 2013
Phase
Phase 1
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 18 to 45 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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:
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  • 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

Who cannot join

  • 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).
Show all 14Show fewer
  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

Other trials in United States

About this study

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.
Read the 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.
Conditions
Alcoholism
Being tested
[11C]flumazenil, Tiagabine
Medical subject headings
Alcoholism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • [11C]flumazenilRadiation

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

  • TiagabineDrug

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

Study groups in NCT01904487
Study groupRoleWhat they receive
PET scansExperimentalBoth alcoholics and healthy controls will undergo two [11C]flumazenil PET scans: one at baseline and one post administration of 0.2 mg/kg Tiagabine.
Receives: Radiation: [11C]flumazenil; Drug: Tiagabine

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 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)

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

    Measured: 1 hour

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jul 2013 (estimated)
  2. Study start19 Apr 2011
  3. Primary completion1 Oct 2013
  4. Study completion1 Oct 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01904487
Sponsor's protocol ID
PRO#10100519
Status last verified
Aug 2017
First submitted
16 Jul 2013
Last updated
29 Aug 2017
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

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

    PubMed 15864554

  • 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.

    PubMed 8947325

  • 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.

    PubMed 8032146

  • 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.

    PubMed 8390063

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing [11C]flumazenil and Tiagabine in people with Alcoholism, run by Rajesh Narendran 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 12 inclusion and 14 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 29 Aug 2017. 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.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01904487, which also lists 4 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 29 Aug 2017.

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