Clinical Trial: Penicillamine Chelation for Children With Lead Poisoning

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

Official Title: A Phase 2/3 Trial of d-Penicillamine Chelation in Lead-Poisoned Children

Brief Summary:

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.

Detailed Summary: 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-
Sponsor: FDA Office of Orphan Products Development

Current Primary Outcome: • 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 ]

Original Primary Outcome: Same as current

Current Secondary Outcome: 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 ]

Original Secondary Outcome: Same as current

Information By: FDA Office of Orphan Products Development

Dates:
Date Received: November 1, 2007
Date Started: September 2007
Date Completion:
Last Updated: March 24, 2015
Last Verified: December 2007