Clinical trial NCT00342849: Treatment of Lead-Exposed Children Trial
Official title: Treatment of Lead-Exposed Children (TLC) Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lead Exposure
Keywords: Clinical Trial
Low-level Lead Poisoning
Chelation
Developmental Assessment
Succimer
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2006-06-21
Enrollment: 780
Sex: ALL
Minimum age (years): 12
Maximum age (years): 33
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The Treatment of Lead-Exposed Children (TLC) clinical trial compared the effect of lead chelation with succimer to placebo therapy. TLC was a randomized, double-blind, placebo-controlled clinical trial with sites in Cincinnati and Columbus, Ohio, Philadelphia, Pennsylvania, Baltimore, Maryland and Newark, New Jersey. The study was designed to test outcomes in IQ, neuropsychological function, behavior, physical growth and blood pressure three years after initiation of treatment. Enrollment was conducted between 1994 and 1997, with completion of the initial three-year follow-up in 2000.

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.

Eligibility criteria: * 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.

Primary outcomes:
measure: Efficacy
timeFrame: Annually
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Newark
country: United States
facility: University of Medicine and Dentistry of New Jersey
state: New Jersey
city: Columbus
country: United States
facility: Childrens Hospital, Columbus
state: Ohio
city: Philadelphia
country: United States
facility: Childrens Hospital, Philadelphia
state: Pennsylvania
Study officials:
affiliation: National Institute of Environmental Health Sciences (NIEHS)
name: Walter Rogan, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
citation: 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.