Penicillamine Chelation for Children With Lead Poisoning

NCT ID: NCT00552630

Last Updated: 2015-03-26

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2/PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30

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 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.

Conditions

Lead Poisoning; Vitamin D Deficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

This group will receive d-penicillamine for 6 weeks

Group Type: EXPERIMENTAL

d-penicillamine

Intervention Type: DEVICE

d-penicillamine twice daily, 15 mg/kg/day, for 6 weeks

2

This group will receive placebo for 6 weeks

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

placebo with same characteristics as drug

Interventions

d-penicillamine

d-penicillamine twice daily, 15 mg/kg/day, for 6 weeks

Intervention Type: DEVICE

placebo

placebo with same characteristics as drug

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bezoloven, Inc.

INDUSTRY

Sponsor Role: collaborator

FDA Office of Orphan Products Development

FED

Sponsor Role: lead

Responsible Party

Children's Hospital Boston

Principal Investigators

Michael W Shannon, MD

Role: STUDY_DIRECTOR

Boston Children's Hospital

Locations

Children's Hospital Boston

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

1R01FD003361-01A1

Identifier Type: FDA

Identifier Source: secondary_id

View Link

3361

Identifier Type: -

Identifier Source: org_study_id