Lead ExposurePhase 3NCT00342849
Treatment of Lead-Exposed Children Trial
A Phase 3 study testing Succimer in people with Lead Exposure, run by National Institute of Environmental Health Sciences (NIEHS) at 4 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 12 to 33 months
- Conditions the study is for
- Lead Exposure
- What is being tested?
- Succimer
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 780 participants
- Where
- 4 sitesUnited States
- Study dates
- 15 Jul 1994to 10 Jun 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 33 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- The study population will reflect the population known to be at greatest risk to lead exposure, i.e., low income, urban, African-American children.
Who cannot join
- 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 locations and contacts
4 sites in 1 country.
United States4 sites
Kennedy Krieger Institute
Baltimore, Maryland, 21205
Childrens Hospital, Columbus
Columbus, Ohio, 43205-2696
University of Medicine and Dentistry of New Jersey
Newark, New Jersey, 07103
Childrens Hospital, Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: Treatment of Lead-Exposed Children (TLC) Trial
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.
Read the 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.
- Conditions
- Lead Exposure
- Being tested
- Succimer, Placebo
- Keywords
- Clinical Trial, Low-level Lead Poisoning, Chelation, Developmental Assessment, Succimer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SuccimerDrug
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.
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Scuccimer Treatment Group Receives: Drug: Succimer |
| 2 | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy
Measured: Annually
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2006 (estimated)
- Study start15 Jul 1994
- Primary completion29 Aug 2007
- Study completion10 Jun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Lead ExposureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 780 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Environmental Health Sciences (NIEHS)
- Sponsor type
- US National Institutes of Health
- Investigators
- Walter Rogan, M.D., Principal investigator, National Institute of Environmental Health Sciences (NIEHS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00342849
- Sponsor's protocol ID
- 999994037
- Other IDs
- OH94-E-N037
- Status last verified
- 10 Jun 2015
- First submitted
- 19 Jun 2006
- Last updated
- 5 Apr 2018
- Results posted
- No
Publications
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. No abstract available.
PubMed 5937397Levitt MF, Goldstein MH, Lenz PR, Wedeen R. Mercurial diuretics. Ann N Y Acad Sci. 1966 Nov 22;139(2):375-87. doi: 10.1111/j.1749-6632.1966.tb41211.x. No abstract available.
PubMed 5230281Wedeen RP, Jernow HI. Autoradiographic study of cellular transport of hippuran-125I in the rat nephron. Am J Physiol. 1968 Apr;214(4):776-85. doi: 10.1152/ajplegacy.1968.214.4.776. No abstract available.
PubMed 5642938Cao 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.
PubMed 23601497Cao 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.
PubMed 20889164
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Lead-Exposed Children (TLC) Trial
- ClinicalTrials.gov ID
- NCT00342849
- Acronym / sponsor ID
- 999994037
- Conditions
- Lead Exposure
- Keywords
- Clinical Trial, Low-level Lead Poisoning, Chelation, Developmental Assessment, Succimer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 780 participants (actual)
- Lead sponsor
- National Institute of Environmental Health Sciences (NIEHS)US National Institutes of Health
- Study start
- 15 Jul 1994
- Primary completion
- 29 Aug 2007 (actual)
- Study completion
- 10 Jun 2015 (actual)
- First posted
- 21 Jun 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: SuccimerScuccimer Treatment Group |
| 2 | Placebo comparator | Drug: PlaceboIn 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. |
Who may qualify
- Ages
- 12 to 33 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- The study population will reflect the population known to be at greatest risk to lead exposure, i.e., low income, urban, African-American children.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SuccimerSuccimer (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. | Drug | 1 |
| Placebo | Drug | 2 |
Primary outcome
Efficacy
Time frame: Annually
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2018.
- Background: PubMed 5937397Littman 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. No abstract available.
- Background: PubMed 5230281Levitt MF, Goldstein MH, Lenz PR, Wedeen R. Mercurial diuretics. Ann N Y Acad Sci. 1966 Nov 22;139(2):375-87. doi: 10.1111/j.1749-6632.1966.tb41211.x. No abstract available.
- Background: PubMed 5642938Wedeen RP, Jernow HI. Autoradiographic study of cellular transport of hippuran-125I in the rat nephron. Am J Physiol. 1968 Apr;214(4):776-85. doi: 10.1152/ajplegacy.1968.214.4.776. No abstract available.
- Derived from this study: PubMed 23601497Cao 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.
- Derived from this study: PubMed 20889164Cao 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Walter Rogan, M.D. principal investigator
National Institute of Environmental Health Sciences (NIEHS)
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Succimer in people with Lead Exposure, run by National Institute of Environmental Health Sciences (NIEHS) at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy (time frame: Annually). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00342849, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2018.