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Dopaminergic Effects on Cortical Function in Tourette's (Levodopa Protocol)

Information source: Washington University School of Medicine
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Tourette Syndrome

Intervention: levodopa solution 2mg/ml for i.v. use (Drug); placebo (Drug)

Phase: N/A

Status: Completed

Sponsored by: Kevin J. Black, MD

Official(s) and/or principal investigator(s):
Kevin J Black, MD, Principal Investigator, Affiliation: Washington Universisty School of Medicine

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). 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 Details

Official title: Dopaminergic Effects on Cortical Function in Tourette's (Levodopa Protocol)

Study design: Allocation: Randomized, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Primary outcome: BOLD (blood oxygen-level dependent) fMRI (functional magnetic resonance imaging) response to a working memory task

Secondary outcome: serum prolactin concentration

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.

Eligibility

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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 Exclusion Criteria:

- 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.

- 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.

Locations and Contacts

Washington Universisty School of Medicine,, St. Louis, Missouri 63110, United States
Additional Information

study description

Tourette syndrome resources

Related 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.

Black 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.

Starting date: February 2006
Last updated: June 11, 2013

Page last updated: August 23, 2015

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