Penicillamine Chelation for Children With Lead Poisoning

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborator:
Bezoloven, Inc.
Information provided by:
FDA Office of Orphan Products Development
ClinicalTrials.gov Identifier:
NCT00552630
First received: November 1, 2007
Last updated: February 6, 2013
Last verified: December 2007
  Purpose

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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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 ] [ Designated as safety issue: Yes ]

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 ] [ Designated as safety issue: Yes ]

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.

  Eligibility

Ages Eligible for Study:   6 Months to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00552630

Locations
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Bezoloven, Inc.
Investigators
Study Director: Michael W Shannon, MD Children's Hospital Boston
  More Information

No publications provided

Responsible Party: Michael Shannon, MD, Children's Hospital Boston
ClinicalTrials.gov Identifier: NCT00552630     History of Changes
Other Study ID Numbers: 3361, 1 R01 FD003361-01A1
Study First Received: November 1, 2007
Last Updated: February 6, 2013
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Lead Poisoning
Poisoning
Vitamin D Deficiency
Substance-Related Disorders
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Penicillamine
Antidotes
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Chelating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 23, 2014