Tourette SyndromeNCT00034398
Study of GABA-A Receptors in the Generation of Tics in Patients With Tourette's Syndrome
An observational study of Tourette Syndrome, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
This study will investigate how the brain generates tics in patients with Tourette's syndrome and which areas of the brain are primarily affected. Tourette's syndrome is a neuropsychiatric disorder characterized by motor and vocal tics, and is associated with behavioral and emotional disturbances, including symptoms… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Tourette Syndrome
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Apr 2002to 11 Mar 2010
- 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 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients will have clinically documented TS as defined by DSM-IV and evaluation of tics severity using Yale Tic Scale. This criterion will be established by the preliminary screening in the NINDS Movement Disorders Outpatient Clinic.
- Patients (either male or female) will range in age from 18 to 65 years. Female patients of child-bearing potential will have a pregnancy test prior to each PET and MRI scan and specific interview prior to the study to ensure that pregnant patients will not participate in the study. Patients will be asked to stop for two weeks prior to the exam any medication that can influence the CNS. Fluoxetine will be stopped for four weeks. They will be asked to abstain from alcohol for one week before the study.
- Seventeen normal controls will be included; controls will be screened in the NINDS Movement Disorders Outpatient Clinic, and will have neurological and physical examinations. Controls with chronic illnesses, taking any medication that affects the CNS will be excluded. They will be asked to abstain from alcohol for one week before the study.
Who cannot join
- Patients younger than 18 years old and older than 65 will be excluded from the study.
- Patients with MRI findings consistent with brain tumors, strokes, trauma or AVMs will be excluded.
- Patients with progressive neurological disorders other than TS will be excluded.
- Patients with a history of significant medical disorders, or requiring chronic treatment with other drugs, which, cannot be stopped, will be excluded.
- Patients with cancer will be excluded.
- Patients incapable of giving an informed consent will be excluded.
- Patients who are pregnant or nursing.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Evaluation of Density and Pattern of Distribution of GABA A Receptors in Brain of Patients With Tourette's Syndrome Studied With PET Using [11C] Flumazenil
This study will investigate how the brain generates tics in patients with Tourette's syndrome and which areas of the brain are primarily affected. Tourette's syndrome is a neuropsychiatric disorder characterized by motor and vocal tics, and is associated with behavioral and emotional disturbances, including symptoms of attention deficit hyperactivity disorder and obsessive-compulsive disorder. This study will examine whether tic generation is related to changes in brain cell receptors for a chemical messenger called gamma-aminobutyric acid (GABA).
Healthy normal volunteers and patients with Tourette's syndrome between 21 and 65 years of age may be eligible for this study. Candidates will be screened with a medical history and physical and neurological examinations.
Read more
Participants will undergo positron emission tomography (PET) scanning to measure brain blood flow. For this procedure, the subject receives an injection of H215O, a radioactive substance similar to water. A special camera detects the radiation emitted by the H215O, allowing measurement of the blood flow. Subjects will receive up to five injections of H215O during the scanning. They will also be injected with another radioactive chemical, (11C) flumazenil, which binds to GABA receptors, to measure the density and distribution of these receptors. This will reveal which areas of the brain in patients with Tourette's syndrome have abnormal binding of flumazenil compared with the brains of healthy control subjects.
During the PET procedure, the subject lies on a table in the PET scanner. A small catheter (plastic tube) is placed in an arm vein for injecting the radioactive tracers, and a mask is placed on the face to help keep the head still during scanning. The mask has large openings for eyes, nose and mouth, so that it does not interfere with talking or breathing. The entire test takes about 3 hours.
On a separate day, participants will also undergo magnetic resonance imaging (MRI), a diagnostic test that uses a magnetic field and radio waves to produce images of the brain. For this procedure, the subject lies still on a stretcher that is moved into the scanner (a narrow cylinder containing the magnet). Earplugs are worn to muffle loud noises caused by electrical switching of radio frequency circuits used in the scanning process. The scan lasts about 45 to 60 minutes.
...
Read the detailed description
The purpose of this study is to determine if symptoms of Tourette's syndrome are due to dysfunction of GABA-ergic neurons causing disinhibition originating in basal ganglia, and involving thalamus, frontal and prefrontal cortices and contributing to tic generation.
The major inhibitory neurotransmitter in central nervous system is gamma-aminobutyric acid (GABA), which acts mainly through the GABA A receptors. Pathological processes involving GABA-ergic neurons cause alterations in the density of GABA A receptors of the targeted neurons. These changes can be visualized and measured with Positron Emission Tomography using as a radioactive ligand [11C] flumazenil. We will examine changes in the density and distribution of GABA A receptors in 17 adult patients with a DSM-IV-TR (American Psychiatric Association 2000) diagnosis of a tic disorder and 17 control subjects. This study should provide new information concerning localization and degree of dysfunction of GABA-ergic neurons in areas involved in Tourette's syndrome, which, in turn, might open new possibilities in pharmacological treatment of this disorder.
- Conditions
- Tourette Syndrome
- Keywords
- Basal Ganglia, Neuroimaging, Inhibitory Neurons, Disinhibition, Tics, Tourette's Syndrome, Tourette Syndrome, Healthy Volunteer, HV, Normal Control
- Medical subject headings
- Tourette Syndrome, Tics
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2002 (estimated)
- Study start24 Apr 2002
- Study completion11 Mar 2010
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 Tourette SyndromeStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- 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
- 26 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00034398
- Sponsor's protocol ID
- 020181
- Other IDs
- 02-N-0181
- Status last verified
- 11 Mar 2010
- First submitted
- 26 Apr 2002
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Biswal B, Ulmer JL, Krippendorf RL, Harsch HH, Daniels DL, Hyde JS, Haughton VM. Abnormal cerebral activation associated with a motor task in Tourette syndrome. AJNR Am J Neuroradiol. 1998 Sep;19(8):1509-12.
PubMed 9763386Bolam JP, Hanley JJ, Booth PA, Bevan MD. Synaptic organisation of the basal ganglia. J Anat. 2000 May;196 ( Pt 4)(Pt 4):527-42. doi: 10.1046/j.1469-7580.2000.19640527.x.
PubMed 10923985Hevers W, Luddens H. The diversity of GABAA receptors. Pharmacological and electrophysiological properties of GABAA channel subtypes. Mol Neurobiol. 1998 Aug;18(1):35-86. doi: 10.1007/BF02741459.
PubMed 9824848
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Density and Pattern of Distribution of GABA A Receptors in Brain of Patients With Tourette's Syndrome Studied With PET Using [11C] Flumazenil
- ClinicalTrials.gov ID
- NCT00034398
- Acronym / sponsor ID
- 020181
- Conditions
- Tourette Syndrome
- Keywords
- Basal Ganglia, Neuroimaging, Inhibitory Neurons, Disinhibition, Tics, Tourette's Syndrome, Tourette Syndrome, Healthy Volunteer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 24 Apr 2002
- Study completion
- 11 Mar 2010
- First posted
- 29 Apr 2002 (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 will investigate how the brain generates tics in patients with Tourette's syndrome and which areas of the brain are primarily affected. Tourette's syndrome is a neuropsychiatric disorder characterized by motor and vocal tics, and is associated with behavioral and emotional disturbances, including symptoms of attention deficit hyperactivity disorder and obsessive-compulsive disorder. This study will examine whether tic generation is related to changes in brain cell receptors for a chemical messenger called gamma-aminobutyric acid (GABA).
Healthy normal volunteers and patients with Tourette's syndrome between 21 and 65 years of age may be eligible for this study. Candidates will be screened with a medical history and physical and neurological examinations.
Participants will undergo positron emission tomography (PET) scanning to measure brain blood flow. For this procedure, the subject receives an injection of H215O, a radioactive substance similar to water. A special camera detects the radiation emitted by the H215O, allowing measurement of the blood flow. Subjects will receive up to five injections of H215O during the scanning. They will also be injected with another radioactive chemical, (11C) flumazenil, which binds to GABA receptors, to measure the density and distribution of these receptors. This will reveal which areas of the brain in patients with Tourette's syndrome have abnormal binding of flumazenil compared with the brains of healthy control subjects.
During the PET procedure, the subject lies on a table in the PET scanner. A small catheter (plastic tube) is placed in an arm vein for injecting the radioactive tracers, and a mask is placed on the face to help keep the head still during scanning. The mask has large openings for eyes, nose and mouth, so that it does not interfere with talking or breathing. The entire test takes about 3 hours.
On a separate day, participants will also undergo magnetic resonance imaging (MRI), a diagnostic test that uses a magnetic field and radio waves to produce images of the brain. For this procedure, the subject lies still on a stretcher that is moved into the scanner (a narrow cylinder containing the magnet). Earplugs are worn to muffle loud noises caused by electrical switching of radio frequency circuits used in the scanning process. The scan lasts about 45 to 60 minutes.
...
Detailed description
The purpose of this study is to determine if symptoms of Tourette's syndrome are due to dysfunction of GABA-ergic neurons causing disinhibition originating in basal ganglia, and involving thalamus, frontal and prefrontal cortices and contributing to tic generation.
The major inhibitory neurotransmitter in central nervous system is gamma-aminobutyric acid (GABA), which acts mainly through the GABA A receptors. Pathological processes involving GABA-ergic neurons cause alterations in the density of GABA A receptors of the targeted neurons. These changes can be visualized and measured with Positron Emission Tomography using as a radioactive ligand [11C] flumazenil. We will examine changes in the density and distribution of GABA A receptors in 17 adult patients with a DSM-IV-TR (American Psychiatric Association 2000) diagnosis of a tic disorder and 17 control subjects. This study should provide new information concerning localization and degree of dysfunction of GABA-ergic neurons in areas involved in Tourette's syndrome, which, in turn, might open new possibilities in pharmacological treatment of this disorder.
Study design
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients will have clinically documented TS as defined by DSM-IV and evaluation of tics severity using Yale Tic Scale. This criterion will be established by the preliminary screening in the NINDS Movement Disorders Outpatient Clinic.
- Patients (either male or female) will range in age from 18 to 65 years. Female patients of child-bearing potential will have a pregnancy test prior to each PET and MRI scan and specific interview prior to the study to ensure that pregnant patients will not participate in the study. Patients will be asked to stop for two weeks prior to the exam any medication that can influence the CNS. Fluoxetine will be stopped for four weeks. They will be asked to abstain from alcohol for one week before the study.
- Seventeen normal controls will be included; controls will be screened in the NINDS Movement Disorders Outpatient Clinic, and will have neurological and physical examinations. Controls with chronic illnesses, taking any medication that affects the CNS will be excluded. They will be asked to abstain from alcohol for one week before the study.
Key exclusion criteria (7 listed)
- Patients younger than 18 years old and older than 65 will be excluded from the study.
- Patients with MRI findings consistent with brain tumors, strokes, trauma or AVMs will be excluded.
- Patients with progressive neurological disorders other than TS will be excluded.
- Patients with a history of significant medical disorders, or requiring chronic treatment with other drugs, which, cannot be stopped, will be excluded.
- Patients with cancer will be excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
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 2 Jul 2017.
- Background: PubMed 9763386Biswal B, Ulmer JL, Krippendorf RL, Harsch HH, Daniels DL, Hyde JS, Haughton VM. Abnormal cerebral activation associated with a motor task in Tourette syndrome. AJNR Am J Neuroradiol. 1998 Sep;19(8):1509-12.
- Background: PubMed 10923985Bolam JP, Hanley JJ, Booth PA, Bevan MD. Synaptic organisation of the basal ganglia. J Anat. 2000 May;196 ( Pt 4)(Pt 4):527-42. doi: 10.1046/j.1469-7580.2000.19640527.x.
- Background: PubMed 9824848Hevers W, Luddens H. The diversity of GABAA receptors. Pharmacological and electrophysiological properties of GABAA channel subtypes. Mol Neurobiol. 1998 Aug;18(1):35-86. doi: 10.1007/BF02741459.
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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 Tourette Syndrome, run by National Institute of Neurological Disorders and Stroke (NINDS) 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 3 inclusion and 7 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 2 Jul 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.
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 NCT00034398, 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 2 Jul 2017.