A Phase 1 interventional study of levodopa solution 2mg/ml for i.v. use and placebo in Tourette Syndrome, sponsored by Washington University School of Medicine. Completed at 1 site in United States. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-02-12.
Sponsored by Washington University School of Medicine · Phase 1, Interventional, and Other
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.
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.
220 studies on the registry are indexed under Tourette Syndrome; 37 are open to participants now.
This study's enrollment of 49 is above the median of 34 across 166 interventional studies indexed under Tourette Syndrome.
Browse Tourette Syndrome studies →Washington University School of Medicine is the lead sponsor of 1,765 studies on the registry; 271 are open to participants now.
Of its 324 completed or terminated interventional studies of FDA-regulated products, 212 (65%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
levodopa solution in saline, given intravenously, dosed as per "final protocol" in Black et al 2003.
Drug: levodopa solution 2mg/ml for i.v. use
normal saline i.v.
Drug: placebo
2mg/mL in normal saline
Also known as: L-DOPA, L-3,4-dihydroxyphenylalanine
normal saline
Also known as: NaCl 0.9% in water
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
serum prolactin concentration
Time frame: approximately 2 hours after infusion begins
Plan to share: 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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Washington University School of Medicine