Treatment of Lead-Exposed Children Trial
Condition: Lead Exposure
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Succimer; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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.
Intervention MeSH terms: Succimer
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Clinical Trial; Low-level Lead Poisoning; Chelation; Developmental Assessment; Succimer