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Penicillamine Chelation for Children With Lead Poisoning

This study has been withdrawn prior to enrollment.
Bezoloven, Inc.
Information provided by:
FDA Office of Orphan Products Development Identifier:
First received: November 1, 2007
Last updated: March 24, 2015
Last verified: December 2007

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.

Condition Intervention Phase
Lead Poisoning
Vitamin D Deficiency
Device: d-penicillamine
Drug: placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2/3 Trial of d-Penicillamine Chelation in Lead-Poisoned Children

Resource links provided by NLM:

Further study details as provided by FDA Office of Orphan Products Development:

Primary Outcome Measures:
  • • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 0
Study Start Date: September 2007
Arms Assigned Interventions
Experimental: 1
This group will receive d-penicillamine for 6 weeks
Device: d-penicillamine
d-penicillamine twice daily, 15 mg/kg/day, for 6 weeks
Placebo Comparator: 2
This group will receive placebo for 6 weeks
Drug: placebo
placebo with same characteristics as drug

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.

Ages Eligible for Study:   6 Months to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its identifier: NCT00552630

United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
FDA Office of Orphan Products Development
Bezoloven, Inc.
Study Director: Michael W Shannon, MD Boston Children’s Hospital
  More Information

Responsible Party: Michael Shannon, MD, Children's Hospital Boston Identifier: NCT00552630     History of Changes
Other Study ID Numbers: 3361
1R01FD003361-01A1 ( US NIH Grant/Contract Award Number )
Study First Received: November 1, 2007
Last Updated: March 24, 2015

Keywords provided by FDA Office of Orphan Products Development:
lead poisoning

Additional relevant MeSH terms:
Vitamin D Deficiency
Lead Poisoning
Deficiency Diseases
Nutrition Disorders
Chemically-Induced Disorders
Protective Agents
Physiological Effects of Drugs
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents processed this record on April 28, 2017