Treatment of Lead-Exposed Children Trial

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00342849
First received: June 19, 2006
Last updated: July 18, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Lead Exposure
Drug: Succimer
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Treatment of Lead-Exposed Children (TLC) Trial

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Efficacy [ Time Frame: Annually ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 1332
Study Start Date: July 1994
Study Completion Date: August 2007
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Scuccimer Treatment Group
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 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.
Drug: Placebo
N/A

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

Ages Eligible for Study:   12 Months to 33 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00342849

Locations
United States, Maryland
Kennedy Krieger Institute
Baltimore, Maryland, United States, 21205
United States, New Jersey
University of Medicine and Dentistry of New Jersey
Newark, New Jersey, United States, 07103
United States, Ohio
Childrens Hospital, Columbus
Columbus, Ohio, United States, 43205-2696
United States, Pennsylvania
Childrens Hospital, Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Investigators
Principal Investigator: Walter Rogan, M.D. National Institute of Environmental Health Sciences (NIEHS)
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00342849     History of Changes
Other Study ID Numbers: 999994037, OH94-E-N037
Study First Received: June 19, 2006
Last Updated: July 18, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Clinical Trial
Low-level Lead Poisoning
Chelation
Developmental Assessment
Succimer

Additional relevant MeSH terms:
Succimer
Antidotes
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014