Treatment of Lead-Exposed Children Trial
Treatment of Lead-Exposed Children (TLC) Trial
Study Overview
Detailed Description
At TLC enrollment, the children were between 12 and 33 months of age with baseline blood lead levels (PbB) between 20 and 44 microg/dl. Of 1,854 referred children who were screened for eligibility, 780 were randomized to the active drug (oral succimer) and placebo groups, stratified by clinical center, body surface area, blood lead level and language spoken at home; only the New Jersey Clinical Center enrolled Spanish-speaking participants. Up to three 26-day courses of succimer or placebo therapy were administered depending on response to treatment in those who were given the active drug. Eighty-nine percent of children had finished treatment by six months, with all children finishing by 13 months after randomization. Residential lead clean-up and nutritional supplementation with multivitamins and minerals were provided to all study children, irrespective of treatment group. Children were followed for three years, with regular physical exams, psychological and developmental testing, and measurement of lead concentration in venous blood. Treatment and follow up are closed for this trial; it is open for scientific analysis and report writing only.
Although succimer lowered blood lead levels much more effectively than placebo, there was no difference between the two groups on any of the psychological tests at three years post randomization, when most children were about five years old. Follow up of TLC children continued into school age. At age seven, 647 of 780 subjects remained in the study. Children were tested at age seven and again at seven and a half on standardized neuropsychological batteries that tap cognition, behavior, learning and memory, attention, and neuromotor skills. While chelation therapy with succimer had lowered average blood lead levels for approximately six months, it resulted in no benefit in cognitive, behavioral and neuromotor endpoints when measured at school ages in these children. These additional follow-up data confirm our previous finding that the TLC regimen of chelation therapy is not associated with neurodevelopmental benefits in children with blood lead levels between 20 and 44 microg/dL.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Maryland
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Baltimore, Maryland, United States, 21205
- Kennedy Krieger Institute
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New Jersey
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Newark, New Jersey, United States, 07103
- University of Medicine and Dentistry of New Jersey
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Ohio
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Columbus, Ohio, United States, 43205-2696
- Childrens Hospital, Columbus
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Childrens Hospital, Philadelphia
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
- INCLUSION CRITERIA:
The study population will reflect the population known to be at greatest risk to lead exposure, i.e., low income, urban, African-American children.
EXCLUSION CRITERIA:
Linguistic minorities will be excluded in all centers except Newark, where Hispanic children make up a sizable portion of the population and will be included.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: 1
Scuccimer Treatment Group
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Succimer (2,3-meso-dimercaptosuccinic acid) is an orally active dithiol compound that is a relatively specific chelating agent for heavy metals, especially lead, arsenic and mercury.
The drug undergoes limited absorption in the gastrointestinal tract and then is rapidly metabolized to mixed disulfides which are eliminated in the urine.
Blood levels decline slowly with an apparent elimination half-life of about 48 hours in adults.
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Placebo Comparator: 2
In order to provide placebo with an odor comparable to that of succimer, the Drug Distribution Center will place a small canister containing 200 mg of active drug into each bottle of placebo drug.
A canister containing 200 mg of placebo will be placed inside each bottle of succimer so that all bottles will appear the same.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
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Efficacy
Time Frame: Annually
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Annually
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Collaborators and Investigators
Investigators
- Principal Investigator: Walter Rogan, M.D., National Institute of Environmental Health Sciences (NIEHS)
Publications and helpful links
General Publications
- Littman E, Goldstein MH, Kasen L, Levitt MF, Wedeen RP. The relationship of the intrarenal distribution of Hg203-chlormerodrin to the diuretic effect. J Pharmacol Exp Ther. 1966 Apr;152(1):130-8. No abstract available.
- Levitt MF, Goldstein MH, Lenz PR, Wedeen R. Mercurial diuretics. Ann N Y Acad Sci. 1966 Nov 22;139(2):375-87. doi: 10.1111/j.1749-6632.1966.tb41211.x. No abstract available.
- Wedeen RP, Jernow HI. Autoradiographic study of cellular transport of hippuran-125I in the rat nephron. Am J Physiol. 1968 Apr;214(4):776-85. doi: 10.1152/ajplegacy.1968.214.4.776. No abstract available.
- Cao Y, Chen A, Bottai M, Caldwell KL, Rogan WJ. The impact of succimer chelation on blood cadmium in children with background exposures: a randomized trial. J Pediatr. 2013 Aug;163(2):598-600. doi: 10.1016/j.jpeds.2013.03.009. Epub 2013 Apr 16.
- Cao Y, Chen A, Jones RL, Radcliffe J, Dietrich KN, Caldwell KL, Peddada S, Rogan WJ. Efficacy of succimer chelation of mercury at background exposures in toddlers: a randomized trial. J Pediatr. 2011 Mar;158(3):480-485.e1. doi: 10.1016/j.jpeds.2010.08.036.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 999994037
- OH94-E-N037
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