Penicillamine Chelation for Children With Lead Poisoning

Sponsor

FDA Office of Orphan Products Development (U.S. Fed)

Overall Status

Withdrawn

CT.gov ID

NCT00552630

Collaborator

Bezoloven, Inc. (Industry)

Enrollment

Location

Arms

Study Details

Study Description

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.

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

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

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. [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. [10 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months to 16 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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