Treatment of Lead-Exposed Children Trial

National Institutes of Health (NIH)

Status and phase: Completed; Phase 3

Conditions: Lead Exposure

Treatments: Drug: Succimer; Drug: Placebo

Study type: Interventional

Funder types: NIH

Identifiers

NCT00342849

999994037

OH94-E-N037

Details and patient eligibility

About

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.

Full 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.

Enrollment: 780 patients

Sex: All

Ages: 12 to 33 months old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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780 participants in 2 patient groups, including a placebo group

1

Experimental group

Description:

Scuccimer Treatment Group

Treatment:

Drug: Succimer

2

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo