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

NCT00634556 | Completed Phase 1 FDA Drug

• 2 other identifiers: 05-0832R01MH073856-01A1
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Tourette Syndrome

Keywords

Tourette Syndrome; fMRI; levodopa; working memory; dopamine

Outcome Measures

Primary Outcomes (1)

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

  From about 30 to 120 minutes after infusion begins

Secondary Outcomes (1)

• serum prolactin concentration

  approximately 2 hours after infusion begins

Study Arms (2)

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.

Drug: levodopa solution 2mg/ml for i.v. use

Placebo

PLACEBO COMPARATOR

normal saline i.v.

Drug: placebo

Interventions

levodopa solution 2mg/ml for i.v. use DRUG

2mg/mL in normal saline

Also known as: L-DOPA, L-3,4-dihydroxyphenylalanine

levodopa solution 2mg/ml for i.v. use

placebo DRUG

normal saline

Also known as: NaCl 0.9% in water

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Washington Universisty School of Medicine,

St Louis, Missouri, 63110, United States

Location

Related Publications (5)

• 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.

  PMID: 15110735 BACKGROUND

• 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. doi: 10.1016/s0165-0270(03)00096-7.

  PMID: 12865145 BACKGROUND

• Campbell 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

  RESULT

• 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/

  RESULT

• Siddiqi SH, Creech ML, Black KJ. Orthostatic stability with intravenous levodopa. PeerJ. 2015 Aug 27;3:e1198. doi: 10.7717/peerj.1198. eCollection 2015.

  PMID: 26336641 RESULT

MeSH Terms

Conditions

Tourette Syndrome

Interventions

Levodopa; Water

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tic Disorders; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds

Study Officials

• Kevin J Black, MD

  Washington Universisty School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2008
• First Posted: March 13, 2008
• Study Start: February 1, 2006
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: February 12, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)