Penicillamine Chelation for Children With Lead Poisoning
March 24, 2015 updated by: FDA Office of Orphan Products Development
A Phase 2/3 Trial of d-Penicillamine Chelation in Lead-Poisoned Children
Childhood Lead Poisoning is a widespread disease that has few effective treatments. The specific aims of this proposed clinical trial are threefold:
- To determine whether a six-week course of a newly formulated d-penicillamine suspension will effectively reduce blood lead level in children aged 6 months to 16 years with blood lead levels of 15-25 μg/dL.
- To determine whether d-penicillamine chelation produces a sustained reduction in blood lead level in comparison with succimer and other lead chelators which always produce a significant post-treatment "rebound".
- To determine whether chelation with d-penicillamine improves the physiologic disturbances that can be measured in children with blood lead levels in this range.
Study Overview
Status
Withdrawn
Conditions
Intervention / Treatment
Detailed Description
Approximately 300,000 children in the US have elevated blood lead levels (10 mcg/dl or greater).
Lead poisoning in children is unequivocally harmful, producing the neurodevelopmental consequences of cognitive losses, attentional difficulties and behavioral disturbances, including antisocial or delinquent tendencies.
Non-neurodevelopmental consequences of lead poisoning include impairment of heme synthesis, reduction in 1- hydroxylation of 25(OH) - cholecalciferol (the Vitamin D precursor) and renal injury that results in microproteniuria, an increased risk of hypertension and a greater likelihood of renal failure in adulthood.
Despite these well-defined toxicities, treatments for childhood lead poisoning have been inadequate.
Currently, chelation therapy is uniformly recommended only for children with severe lead poisoning (blood lead > 45 mcg/dl).
Approved chelating agents for severe plumbism are CaNa2EDTA and succimer.
For children with blood lead levels less than 45 mcg/dl treatment is fraught with difficulties including inconsistent recommendations by clinical experts, lack of proven benefit of chelation and the absence of a chelating agent approved for use in this range.
d-Penicillamine is a lead chelator that has been used off-label for almost 4 decades.
Several studies have suggested that d-penicillamine is both safe and effective in the treatment of low-level lead poisoning.
We propose to evaluate, in a Phase II/III randomized, placebo-controlled clinical trial, the effectiveness of d-penicillamine in 50 children aged 6 months to 16 years with blood lead levels 15-25 mcg/dl.
The d-penicillamine product will be a newly developed, IND-approved liquid formulation.
The study will be performed in the Pediatric Environmental Health Center of Children's Hospital Boston.
The primary outcome measure will be the ability of a 6-week course of d-penicillamine to produce sustained reductions in blood lead level.
Secondary outcome measures will be normalization of non-neurodevelopmental physiologic aberrations known to occur with lead poisoning, specifically abnormalities in heme and Vitamin D synthesis.
If this clinical trial demonstrates safety and efficacy, d-penicillamine will potentially provide another option among the limited treatment choices for lead-poisoned children.
This trial will also provide a basis for examining the drug's efficacy in improving neurodevelopment outcome in children exposed to harmful amounts of lead.
Study Type
Interventional
Phase
- Phase 2
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Massachusetts
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Boston, Massachusetts, United States, 02115
- Children's Hospital Boston
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
6 months to 16 years (Child)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Potential subjects will be children 6 months to 16 years of age with blood lead level 15-25 mcg/dL on two separate occasions separated by at least two weeks
Exclusion Criteria:
- allergic to d-penicillamine
- renal insufficiency
- taking immunosuppressive agents
- pre-existing idiopathic thrombocytopenia (platelet count < 100,000/mm3) or leukopenia (WBC count < 5,000/mm3 or polymorphonuclear leukocyte count < 1000/mm3)
- blood lead level on the day of the initial clinic visit is below15 μg/dL or above 25 μg/dL
- blood lead level at the two-week follow up visit rises above 25 mcg/dL or falls below 15 mcg/dL
- currently undergoing chelation or have had chelation therapy in the previous two months
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: 1
This group will receive d-penicillamine for 6 weeks
|
d-penicillamine twice daily, 15 mg/kg/day, for 6 weeks
|
|
Placebo Comparator: 2
This group will receive placebo for 6 weeks
|
placebo with same characteristics as drug
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
• To determine whether a six-week course of a newly formulated d-penicillamine suspension will effectively reduce blood lead level in children aged 6 months to 16 years with blood lead levels of 15-25 μg/dL.
Time Frame: 6 weeks
|
6 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
To determine whether d-penicillamine produces a sustained reduction in blood lead level and improves the physiologic disturbances that can be measured in children with blood lead levels in this range.
Time Frame: 10 weeks
|
10 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Study Director: Michael W Shannon, MD, Boston Children's Hospital
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
September 1, 2007
Study Registration Dates
First Submitted
November 1, 2007
First Submitted That Met QC Criteria
November 1, 2007
First Posted (Estimate)
November 2, 2007
Study Record Updates
Last Update Posted (Estimate)
March 26, 2015
Last Update Submitted That Met QC Criteria
March 24, 2015
Last Verified
December 1, 2007
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Chemically-Induced Disorders
- Nutrition Disorders
- Avitaminosis
- Deficiency Diseases
- Malnutrition
- Heavy Metal Poisoning
- Poisoning
- Vitamin D Deficiency
- Lead Poisoning
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Protective Agents
- Antidotes
- Chelating Agents
- Sequestering Agents
- Penicillamine
Other Study ID Numbers
- 3361
- 1R01FD003361-01A1 (U.S. FDA Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.