Treatment of Lead-Exposed Children Trial

Lead Exposure Clinical Trial

Official title:

Treatment of Lead-Exposed Children (TLC) Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00342849
• Other study ID #: 999994037
• Secondary ID: OH94-E-N037
• Status: Completed
• Phase: Phase 3
• First received: June 19, 2006
• Last updated: April 4, 2018
• Start date: July 15, 1994
• Est. completion date: June 10, 2015

Study information

• Verified date: June 10, 2015
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 780
• Est. completion date: June 10, 2015
• Est. primary completion date: August 29, 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Months to 33 Months

Eligibility

• 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.

Related Conditions & MeSH terms

• Lead Exposure

Intervention

Drug:
• Succimer
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.
• Placebo

Locations

Country	Name	City	State
United States	Kennedy Krieger Institute	Baltimore	Maryland
United States	Childrens Hospital, Columbus	Columbus	Ohio
United States	University of Medicine and Dentistry of New Jersey	Newark	New Jersey
United States	Childrens Hospital, Philadelphia	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Environmental Health Sciences (NIEHS)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Levitt MF, Goldstein MH, Lenz PR, Wedeen R. Mercurial diuretics. Ann N Y Acad Sci. 1966 Nov 22;139(2):375-87. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy		Annually