Tourette SyndromePhase 1TSfMRINCT00634556
Dopaminergic Effects on Cortical Function in Tourette's (Levodopa Protocol)
A Phase 1 study testing levodopa solution 2mg/ml for i.v. use in people with Tourette Syndrome, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Dr. Kevin J. Black at Washington University is conducting a study to learn whether we can use MRI scans to test dopamine function in the brain and to determine whether the brain performs memory tasks differently in Tourette Syndrome (TS). Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Tourette Syndrome
- What is being tested?
- levodopa solution 2mg/ml for i.v. use
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 49 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2006to Oct 2010
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age 18-55.
- Tic subjects must meet DSM-IV-TR criteria for a chronic tic disorder.
- Controls are matched for age (within 4 years), sex, handedness (right-handed, non-right-handed), and education (within 2 years), and if possible for race and ethnicity
Who cannot join
- Inability to give competent informed consent.
- Lactation, pregnancy or possibility of pregnancy.
- Contraindication to MRI (pacemaker; nontrivial metallic foreign bodies; significant claustrophobia).
- Contraindication to levodopa or carbidopa (known allergy).
- Significant neurological disease (not counting the tic disorder).
- Current renal, cardiac or hepatic disease that would make study participation less safe.
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- Head injury with loss of consciousness for more than 5 minutes or with neurological sequelae.
- Lifetime history of serious lifetime psychopathology or substance abuse. (Specific exclusions are: lifetime diagnosis of mental retardation, autism, psychosis, mania, somatization disorder, panic disorder, social phobia [excludes symptoms present only when treated with a neuroleptic], anorexia nervosa or bulimia, drug or alcohol dependence, antisocial personality disorder, or dementia, or current major depression.)
- Depot neuroleptics in the past 6 months.
- Other antipsychotics within the past 2 weeks.
- Behavioral therapy for Tics of OCD sx in the past 2 weeks.
- For one half of the subjects in each diagnostic group: any brain-active medications within the past 2 weeks. For the remaining subjects: neuroactive medications in the past 2 weeks other than SSRIs, alpha-2 agonists, norepinephrine reuptake inhibitors, or clonazepam.
- Additional exclusions for controls: No history of tic disorder, OCD or ADHD. If under age 25, no first-degree relative with a tic disorder. No exposure to neuroleptics in the past year and none ever for a period exceeding a week.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington Universisty School of Medicine,
St Louis, Missouri, 63110
About this study
Dr. Kevin J. Black at Washington University is conducting a study to learn whether we can use MRI scans to test dopamine function in the brain and to determine whether the brain performs memory tasks differently in Tourette Syndrome (TS). TS is a movement disorder characterized by vocal tics (sounds) and motor tics (movements). We will measure how and where brain activity changes using magnetic resonance imaging (MRI) scans during memory tasks and after taking levodopa. Levodopa is a drug commonly used for the treatment of Parkinson's disease (PD), a very different movement disorder.
Read the detailed description
Clinical observations suggest that in TS there is abnormal function in the brain's motor system that can be modified by manipulating dopamine. My colleagues and I have hypothesized that nonmotor brain systems may also show dopamine-sensitive functional abnormalities. Recently we tested this hypothesis using functional magnetic resonance imaging (fMRI). A cognitive task involving working memory (WM) produced excessive activation of several brain regions in TS subjects compared to controls, but this excessive activation normalized after administering the dopamine precursor levodopa (Hershey et al, 2004).
We can state the following focused hypotheses and corresponding specific aims:
(1) In TS, normal performance during a working memory (WM) task requires greater activation of specific brain regions (parietal cortex, medial frontal cortex and thalamus) than in control subjects, and this excess fMRI response is reduced (improved) by exogenous levodopa. (2) These fMRI results in TS relate specifically to WM, to TS, and to dopamine receptor activation, rather than to non-WM components of the cognitive task, comorbidity, placebo effects, or other confounds.
Specific Aim 1. Test whether the preliminary fMRI results generalize to a larger and more representative sample of adults with TS.
Specific Aim 2. Clarify the variables that interact to produce the differential fMRI responses to a WM task and levodopa observed in TS subjects vs controls.
2a. Task components. Control for non-WM components of the task and delineate a "dose-response" curve for effects of WM load on fMRI responses.
2b. Clinical variables. Test whether the fMRI results in our preliminary data are associated with TS itself rather than with comorbid conditions, treatment history, demographic variables, or state variables such as current tic severity / tic suppression.
2c. Pharmacology. Test whether the post-levodopa changes in WM-related fMRI signal relate specifically to levodopa plasma concentration (rather than practice effects, placebo effects, or passage of time) and are replicated by a nonselective dopamine receptor agonist or by a dopamine D2/D3/D4 agonist.
- Conditions
- Tourette Syndrome
- Being tested
- levodopa solution 2mg/ml for i.v. use, placebo
- Keywords
- Tourette Syndrome, fMRI, levodopa, working memory, dopamine
- Medical subject headings
- Tourette Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
levodopa solution 2mg/ml for i.v. useDrug
Also called L-DOPA, L-3,4-dihydroxyphenylalanine
2mg/mL in normal saline
placeboDrug
Also called NaCl 0.9% in water
normal saline
| Study group | Role | What they receive |
|---|---|---|
| levodopa solution 2mg/ml for i.v. use | Experimental | levodopa solution in saline, given intravenously, dosed as per "final protocol" in Black et al 2003. Receives: Drug: levodopa solution 2mg/ml for i.v. use |
| Placebo | Placebo comparator | normal saline i.v. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
BOLD (blood oxygen-level dependent) fMRI (functional magnetic resonance imaging) response to a working memory task
Measured: From about 30 to 120 minutes after infusion begins
Secondary outcomes (1)
serum prolactin concentration
Measured: approximately 2 hours after infusion begins
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2008 (estimated)
- Study startFeb 2006
- Primary completionOct 2010
- Study completionOct 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)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 Washington University School of MedicineThe 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Kevin J Black, MD, Principal investigator, Washington Universisty School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00634556
- Sponsor's protocol ID
- 05-0832
- Other IDs
- R01MH073856-01A1
- Acronym
- TSfMRI
- Status last verified
- Feb 2018
- First submitted
- 5 Mar 2008
- Last updated
- 12 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Vital signs IPD are shared at: Siddiqi SH, Creech ML, Black KJ. Orthostatic stability with intravenous levodopa. PeerJ. 2015 Aug 27;3:e1198. doi: 10.7717/peerj.1198. eCollection 2015. PubMed ID: 26336641 There is no plan to share other IPD.
Publications
Hershey T, Black KJ, Hartlein JM, Barch DM, Braver TS, Carl JL, Perlmutter JS. Cognitive-pharmacologic functional magnetic resonance imaging in tourette syndrome: a pilot study. Biol Psychiatry. 2004 May 1;55(9):916-25. doi: 10.1016/j.biopsych.2004.01.003.
PubMed 15110735Black KJ, Carl JL, Hartlein JM, Warren SL, Hershey T, Perlmutter JS. Rapid intravenous loading of levodopa for human research: clinical results. J Neurosci Methods. 2003 Jul 15;127(1):19-29. doi: 10.1016/s0165-0270(03)00096-7.
PubMed 12865145Campbell M, Koller J, Shipley E, Creech M, Hershey T, Black K. Dopaminergic modulation of working memory in Tourette's syndrome [abstract]. J Neuropsychiatry Clin Neurosci 20(2):232, 2008. http://neuro.psychiatryonline.org/article.aspx?articleid=103362
Black KJ, Campbell MC, Koller JM, Schneider B, Hershey T. Dopaminergic modulation of working-memory-related cortical activity in Tourette syndrome. Annual meeting, Society for Neuroscience, Chicago, 20 Oct 2009. http://www.sfn.org/
Siddiqi SH, Creech ML, Black KJ. Orthostatic stability with intravenous levodopa. PeerJ. 2015 Aug 27;3:e1198. doi: 10.7717/peerj.1198. eCollection 2015.
PubMed 26336641
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dopaminergic Effects on Cortical Function in Tourette's (Levodopa Protocol)
- ClinicalTrials.gov ID
- NCT00634556
- Acronym / sponsor ID
- TSfMRI / 05-0832
- Conditions
- Tourette Syndrome
- Keywords
- Tourette Syndrome, fMRI, levodopa, working memory, dopamine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Feb 2006
- Primary completion
- Oct 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 13 Mar 2008 (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.
Dr. Kevin J. Black at Washington University is conducting a study to learn whether we can use MRI scans to test dopamine function in the brain and to determine whether the brain performs memory tasks differently in Tourette Syndrome (TS). TS is a movement disorder characterized by vocal tics (sounds) and motor tics (movements). We will measure how and where brain activity changes using magnetic resonance imaging (MRI) scans during memory tasks and after taking levodopa. Levodopa is a drug commonly used for the treatment of Parkinson's disease (PD), a very different movement disorder.
Detailed description
Clinical observations suggest that in TS there is abnormal function in the brain's motor system that can be modified by manipulating dopamine. My colleagues and I have hypothesized that nonmotor brain systems may also show dopamine-sensitive functional abnormalities. Recently we tested this hypothesis using functional magnetic resonance imaging (fMRI). A cognitive task involving working memory (WM) produced excessive activation of several brain regions in TS subjects compared to controls, but this excessive activation normalized after administering the dopamine precursor levodopa (Hershey et al, 2004).
We can state the following focused hypotheses and corresponding specific aims:
(1) In TS, normal performance during a working memory (WM) task requires greater activation of specific brain regions (parietal cortex, medial frontal cortex and thalamus) than in control subjects, and this excess fMRI response is reduced (improved) by exogenous levodopa. (2) These fMRI results in TS relate specifically to WM, to TS, and to dopamine receptor activation, rather than to non-WM components of the cognitive task, comorbidity, placebo effects, or other confounds.
Specific Aim 1. Test whether the preliminary fMRI results generalize to a larger and more representative sample of adults with TS.
Specific Aim 2. Clarify the variables that interact to produce the differential fMRI responses to a WM task and levodopa observed in TS subjects vs controls.
2a. Task components. Control for non-WM components of the task and delineate a "dose-response" curve for effects of WM load on fMRI responses.
2b. Clinical variables. Test whether the fMRI results in our preliminary data are associated with TS itself rather than with comorbid conditions, treatment history, demographic variables, or state variables such as current tic severity / tic suppression.
2c. Pharmacology. Test whether the post-levodopa changes in WM-related fMRI signal relate specifically to levodopa plasma concentration (rather than practice effects, placebo effects, or passage of time) and are replicated by a nonselective dopamine receptor agonist or by a dopamine D2/D3/D4 agonist.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| levodopa solution 2mg/ml for i.v. use | Experimental | Drug: levodopa solution 2mg/ml for i.v. uselevodopa solution in saline, given intravenously, dosed as per "final protocol" in Black et al 2003. |
| Placebo | Placebo comparator | Drug: placebonormal saline i.v. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Age 18-55.
- Tic subjects must meet DSM-IV-TR criteria for a chronic tic disorder.
- Controls are matched for age (within 4 years), sex, handedness (right-handed, non-right-handed), and education (within 2 years), and if possible for race and ethnicity
Key exclusion criteria (13 listed)
- Inability to give competent informed consent.
- Lactation, pregnancy or possibility of pregnancy.
- Contraindication to MRI (pacemaker; nontrivial metallic foreign bodies; significant claustrophobia).
- Contraindication to levodopa or carbidopa (known allergy).
- Significant neurological disease (not counting the tic disorder).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| levodopa solution 2mg/ml for i.v. useAlso: L-DOPA, L-3,4-dihydroxyphenylalanine2mg/mL in normal saline | Drug | levodopa solution 2mg/ml for i.v. use |
| placeboAlso: NaCl 0.9% in waternormal saline | Drug | Placebo |
Primary outcome
BOLD (blood oxygen-level dependent) fMRI (functional magnetic resonance imaging) response to a working memory task
Time frame: From about 30 to 120 minutes after infusion begins
1 secondary outcome
serum prolactin concentration
Time frame: approximately 2 hours after infusion begins
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 12 Feb 2018.
- Background: PubMed 15110735Hershey T, Black KJ, Hartlein JM, Barch DM, Braver TS, Carl JL, Perlmutter JS. Cognitive-pharmacologic functional magnetic resonance imaging in tourette syndrome: a pilot study. Biol Psychiatry. 2004 May 1;55(9):916-25. doi: 10.1016/j.biopsych.2004.01.003.
- Background: PubMed 12865145Black KJ, Carl JL, Hartlein JM, Warren SL, Hershey T, Perlmutter JS. Rapid intravenous loading of levodopa for human research: clinical results. J Neurosci Methods. 2003 Jul 15;127(1):19-29. doi: 10.1016/s0165-0270(03)00096-7.
- Results publicationCampbell M, Koller J, Shipley E, Creech M, Hershey T, Black K. Dopaminergic modulation of working memory in Tourette's syndrome [abstract]. J Neuropsychiatry Clin Neurosci 20(2):232, 2008. http://neuro.psychiatryonline.org/article.aspx?articleid=103362
- Results publicationBlack KJ, Campbell MC, Koller JM, Schneider B, Hershey T. Dopaminergic modulation of working-memory-related cortical activity in Tourette syndrome. Annual meeting, Society for Neuroscience, Chicago, 20 Oct 2009. http://www.sfn.org/
- Results publication: PubMed 26336641Siddiqi SH, Creech ML, Black KJ. Orthostatic stability with intravenous levodopa. PeerJ. 2015 Aug 27;3:e1198. doi: 10.7717/peerj.1198. eCollection 2015.
- Individual participant dataSharing planned: No. Vital signs IPD are shared at: Siddiqi SH, Creech ML, Black KJ. Orthostatic stability with intravenous levodopa. PeerJ. 2015 Aug 27;3:e1198. doi: 10.7717/peerj.1198. eCollection 2015. PubMed ID: 26336641 There is no plan to share other IPD.
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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.
Kevin J Black, MD principal investigator
Washington Universisty School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing levodopa solution 2mg/ml for i.v. use in people with Tourette Syndrome, run by Washington University School of Medicine 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 13 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 12 Feb 2018. 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. Some participants in this study may receive a placebo. 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?
BOLD (blood oxygen-level dependent) fMRI (functional magnetic resonance imaging) response to a working memory task (time frame: From about 30 to 120 minutes after infusion begins). 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 NCT00634556, which also lists 5 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 12 Feb 2018.