Developmental StutteringNCT00024960
Dopamine Function in Developmental Stuttering
An observational study of Developmental Stuttering, run by National Institute on Deafness and Other Communication Disorders (NIDCD) at 1 site in United States.
Trial summary
This study will use positron emission tomography (PET) to examine the role of the chemical messenger dopamine in stuttering. It will measure and compare the number of dopamine receptors and the amount of dopamine released in the brains of stutterers with that of normal volunteers. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Developmental Stuttering
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Oct 2001to 29 Oct 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 55 years
- All sexes
- No healthy volunteers
- Adult
- INCLUSION AND EXCLUSION CRITERIA - STUTTERING AND CONTROL SUBJECTS:
Subjects must be between the ages of 18 and 55.
Subjects must be in good general health except for the primary neurological diagnosis of stuttering.
Subjects may not have evidence of hypertension or cardiovascular disease, cerebrovascular disease or hyperthyroidism.
EKG and thyroid function tests must be within normal limits.
Subjects must have no history of traumatic head injury including any head trauma that resulted in loss of consciousness or history of substance abuse, including alcohol (excluding caffeine).
Subjects will be screened for history of psychiatric illness, such as depression, anxiety or obsessive-compulsive disorders according to DSM-IV; subjects with such diagnoses will be excluded.
Subjects will be screened for a past medical history or family history of speech-language disorders; subjects with a personal or significant family history of speech-language disorders unrelated to the diagnoses of stuttering or aphasia will be excluded. Also those subjects with immediate family members having a significant history of heart attack or stroke will be excluded.
Women who are pregnant or currently breast-feeding will be excluded from this study.
Subjects with pacemakers, aneurysm clips, cochlear implants, shrapnel fragments or have a significant history of exposure to small metallic objects, which might have become lodged in the tissues of the head, or neck will be excluded due to the MRI.
The following criteria must be met to identify an individual who stutters:
Affected individual regards him or herself as having a stuttering disorder, reporting instances during speech where they know exactly what they wish to say, but can not be due to production impairment; these instances may be accompanied by a feeling of tension somewhere within the vocal tract. Individuals may have sought treatment for their stuttering.
Speech-language pathologist confirms diagnosis of stuttering disorder in affected individuals, documenting presence of silent or sound prolongations, syllable repetitions, word/phrase repetitions, interjections and pauses at non-linguistic loci in their speech. Affected individuals will be at least 5% dysfluent in at least 2 of the speaking tasks used to assess fluency.
Recovered stutterers must have a history of stuttering documented by the speech pathologist responsible for evaluation or treatment of this individual during childhood. A history of stuttering may alternatively be documented by a parent and at least one other family member or friend. Recovered individuals must report that they no longer monitor their speech on a routine basis or use speech therapy techniques while speaking.
Speech-language pathologist must judge that recovered individuals are currently free of overt stuttering (less than 1 stuttering behavior/100 words).
Onset of stuttering in both affected individuals and recovered stutterers must have occurred in childhood (between 3 and 10 years-of-age), unrelated to psychological or neurological trauma.
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: Assessment of Pre- and Post-Synaptic Dopamine Function in Developmental Stuttering Using 11C-Raclopride and Positron Emission Tomography
This study will use positron emission tomography (PET) to examine the role of the chemical messenger dopamine in stuttering. It will measure and compare the number of dopamine receptors and the amount of dopamine released in the brains of stutterers with that of normal volunteers. The results may provide information about how drugs that block dopamine's effect might work to enable fluent speech.
Healthy normal volunteers and people with developmental stuttering between the ages of 18 and 55 may be eligible for this study. Candidates will be screened with a medical history and possibly a physical examination and laboratory tests.
Read more
Participants will have a hearing test and cognitive function tests to measure speech, language, memory and visual skills. In addition, they will undergo the following procedures:
- PET scanning to measure brain blood flow and dopamine distribution in the brain. PET uses radioactive materials to show cellular activity in specific tissues of the body. Before starting the procedure, a thin plastic tube (intravenous, or IV line) is placed in a vein in each arm of the subject and a special plastic mask is molded to the face. (The mask is used to insure that the position of the head does not change during the scan.) For the scan, the subject lies on a bed that is positioned into the scanner. A preliminary "transmission" scan is done to make necessary measurements and adjustments. Following this scan, 10 injections of radioactive water are given through an IV line. During these injections, the subject performs a series of speech tasks-such as singing, telling a story, or reciting nursery rhymes-that will elicit either fluent speech or stuttering. A special camera detects the radiation emitted and produces images of brain blood flow during stuttering and normal speech. Next, raclopride (a radioactive material that attaches to dopamine receptors on the cell surface) is given through an IV line and more pictures of the brain are taken. Fifty minutes after the raclopride injection, amphetamine-a drug that increases brain dopamine levels-is injected through the other IV line and more pictures are taken to show dopamine distribution in the brain. Fifty minutes after the amphetamine infusion, the IV lines are removed.
- Magnetic resonance imaging (MRI) of the brain to complement and interpret information from the PET scans. MRI uses a strong magnetic field and radio waves to show structural changes in tissues. The subject lies on a table surrounded by a metal cylinder (the scanner). During the procedure, which may take from 20 minutes to 2 hours, subjects may be asked to perform simple tasks, such as speaking or moving their arms. They can speak with a staff member via an intercom at all times during the procedure and can be moved out of the machine any time they request.
Participants may be asked to return for up to two scanning sessions within a year. For these scans, only 1 injection of radioactive water will be given.
Read the detailed description
Clinical responses to dopamine (DA) antagonists from patients with developmental stuttering suggest that the pathophysiology of this disorder may involve an abnormality of central DA systems. This hypothesis has never been tested using methods that measure both pre- and postsynaptic dopaminergic mechanisms within the CNS. A new PET technique permits evaluation of these mechanisms in human subjects. 11C raclopride, a relatively selective D2 receptor antagonist, is used to estimate postsynaptic DA receptor binding potential following establishment of equilibrium conditions. A low dose bolus of amphetamine is then used to release DA from the presynaptic neuron and displace the ligand from postsynaptic binding sites, in order to estimate the size of the releasable presynaptic DA pool. We propose to use this technique in individuals with developmental stuttering and control subjects to test the hypothesis that stuttering is due to dopaminergic hyperactivity within the CNS. The cause of this hyperactivity is hypothesized to be due to an increase in either the postsynaptic binding potential or the size of the releasable presynaptic dopamine vesicular pool (in which case postsynaptic receptors may be down regulated). Our studies should help conjoin and modify this pathophysiological model. If low dose amphetamine can be used to demonstrate a difference between people who stutter and controls, a second study will be conducted to see if stuttering behavior per se has a measurable effect on DA release that differs from the effect of similar speech tasks in control subjects. Lastly, in a third study, DA releasability will be measured in those recovered from stuttering and those not affected by stuttering but are part of families who have many members that stutter. The culmination of these studies is to attempt isolation of a DA marker that can be used as a phenotyping tool in genetic studies of stuttering.
- Conditions
- Developmental Stuttering
- Keywords
- Speech, Motor Control, Phenotype, Dysfluency, Fluency, Stuttering, Healthy Volunteer, HV, Normal Control
- Medical subject headings
- Stuttering, Speech
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2001 (estimated)
- Study start3 Oct 2001
- Study completion29 Oct 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 Developmental StutteringStudies of the same condition, open and under way.
- 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
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Deafness and Other Communication Disorders (NIDCD)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00024960
- Sponsor's protocol ID
- 020008
- Other IDs
- 02-DC-0008
- Status last verified
- 29 Oct 2010
- First submitted
- 9 Oct 2001
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Andrews G, Craig A, Feyer AM, Hoddinott S, Howie P, Neilson M. Stuttering: a review of research findings and theories circa 1982. J Speech Hear Disord. 1983 Aug;48(3):226-46. doi: 10.1044/jshd.4803.226.
PubMed 6353066Ambrose NG, Yairi E, Cox N. Genetic aspects of early childhood stuttering. J Speech Hear Res. 1993 Aug;36(4):701-6. doi: 10.1044/jshr.3604.701.
PubMed 8377483Allsopp LF, Cooper GL, Poole PH. Clomipramine and diazepam in the treatment of agoraphobia and social phobia in general practice. Curr Med Res Opin. 1984;9(1):64-70. doi: 10.1185/03007998409109561.
PubMed 6373161
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
- Assessment of Pre- and Post-Synaptic Dopamine Function in Developmental Stuttering Using 11C-Raclopride and Positron Emission Tomography
- ClinicalTrials.gov ID
- NCT00024960
- Acronym / sponsor ID
- 020008
- Conditions
- Developmental Stuttering
- Keywords
- Speech, Motor Control, Phenotype, Dysfluency, Fluency, Stuttering, Healthy Volunteer, HV
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- National Institute on Deafness and Other Communication Disorders (NIDCD)US National Institutes of Health
- Study start
- 3 Oct 2001
- Study completion
- 29 Oct 2010
- First posted
- 10 Oct 2001 (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 use positron emission tomography (PET) to examine the role of the chemical messenger dopamine in stuttering. It will measure and compare the number of dopamine receptors and the amount of dopamine released in the brains of stutterers with that of normal volunteers. The results may provide information about how drugs that block dopamine's effect might work to enable fluent speech.
Healthy normal volunteers and people with developmental stuttering between the ages of 18 and 55 may be eligible for this study. Candidates will be screened with a medical history and possibly a physical examination and laboratory tests.
Participants will have a hearing test and cognitive function tests to measure speech, language, memory and visual skills. In addition, they will undergo the following procedures:
- PET scanning to measure brain blood flow and dopamine distribution in the brain. PET uses radioactive materials to show cellular activity in specific tissues of the body. Before starting the procedure, a thin plastic tube (intravenous, or IV line) is placed in a vein in each arm of the subject and a special plastic mask is molded to the face. (The mask is used to insure that the position of the head does not change during the scan.) For the scan, the subject lies on a bed that is positioned into the scanner. A preliminary "transmission" scan is done to make necessary measurements and adjustments. Following this scan, 10 injections of radioactive water are given through an IV line. During these injections, the subject performs a series of speech tasks-such as singing, telling a story, or reciting nursery rhymes-that will elicit either fluent speech or stuttering. A special camera detects the radiation emitted and produces images of brain blood flow during stuttering and normal speech. Next, raclopride (a radioactive material that attaches to dopamine receptors on the cell surface) is given through an IV line and more pictures of the brain are taken. Fifty minutes after the raclopride injection, amphetamine-a drug that increases brain dopamine levels-is injected through the other IV line and more pictures are taken to show dopamine distribution in the brain. Fifty minutes after the amphetamine infusion, the IV lines are removed.
- Magnetic resonance imaging (MRI) of the brain to complement and interpret information from the PET scans. MRI uses a strong magnetic field and radio waves to show structural changes in tissues. The subject lies on a table surrounded by a metal cylinder (the scanner). During the procedure, which may take from 20 minutes to 2 hours, subjects may be asked to perform simple tasks, such as speaking or moving their arms. They can speak with a staff member via an intercom at all times during the procedure and can be moved out of the machine any time they request.
Participants may be asked to return for up to two scanning sessions within a year. For these scans, only 1 injection of radioactive water will be given.
Detailed description
Clinical responses to dopamine (DA) antagonists from patients with developmental stuttering suggest that the pathophysiology of this disorder may involve an abnormality of central DA systems. This hypothesis has never been tested using methods that measure both pre- and postsynaptic dopaminergic mechanisms within the CNS. A new PET technique permits evaluation of these mechanisms in human subjects. 11C raclopride, a relatively selective D2 receptor antagonist, is used to estimate postsynaptic DA receptor binding potential following establishment of equilibrium conditions. A low dose bolus of amphetamine is then used to release DA from the presynaptic neuron and displace the ligand from postsynaptic binding sites, in order to estimate the size of the releasable presynaptic DA pool. We propose to use this technique in individuals with developmental stuttering and control subjects to test the hypothesis that stuttering is due to dopaminergic hyperactivity within the CNS. The cause of this hyperactivity is hypothesized to be due to an increase in either the postsynaptic binding potential or the size of the releasable presynaptic dopamine vesicular pool (in which case postsynaptic receptors may be down regulated). Our studies should help conjoin and modify this pathophysiological model. If low dose amphetamine can be used to demonstrate a difference between people who stutter and controls, a second study will be conducted to see if stuttering behavior per se has a measurable effect on DA release that differs from the effect of similar speech tasks in control subjects. Lastly, in a third study, DA releasability will be measured in those recovered from stuttering and those not affected by stuttering but are part of families who have many members that stutter. The culmination of these studies is to attempt isolation of a DA marker that can be used as a phenotyping tool in genetic studies of stuttering.
Study design
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
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 6353066Andrews G, Craig A, Feyer AM, Hoddinott S, Howie P, Neilson M. Stuttering: a review of research findings and theories circa 1982. J Speech Hear Disord. 1983 Aug;48(3):226-46. doi: 10.1044/jshd.4803.226.
- Background: PubMed 8377483Ambrose NG, Yairi E, Cox N. Genetic aspects of early childhood stuttering. J Speech Hear Res. 1993 Aug;36(4):701-6. doi: 10.1044/jshr.3604.701.
- Background: PubMed 6373161Allsopp LF, Cooper GL, Poole PH. Clomipramine and diazepam in the treatment of agoraphobia and social phobia in general practice. Curr Med Res Opin. 1984;9(1):64-70. doi: 10.1185/03007998409109561.
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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 Developmental Stuttering, run by National Institute on Deafness and Other Communication Disorders (NIDCD) 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?
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 NCT00024960, 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; AzTrials last refreshed its copy on 27 Oct 2026.