Penicillamine Chelation for Children With Lead Poisoning
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.
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
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Conditions
Lead Poisoning
Intervention
d-penicillamine, placebo
Location
Children's Hospital Boston
Boston
Massachusetts
United States
02115
Status
Active, not recruiting
Source
FDA Office of Orphan Products Development
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00552630
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Lead Poisoning, Nervous System
Injury to the nervous system secondary to exposure to lead compounds. Two distinct clinical patterns occur in children (LEAD POISONING, NERVOUS SYSTEM, CHILDHOOD) and adults (LEAD POISONING, NERVOUS SYSTEM, ADULT). In children, lead poisoning typically produces an encephalopathy. In adults, exposure to toxic levels of lead is associated with a peripheral neuropathy.
Lead Poisoning, Nervous System, Childhood
Neurologic disorders occurring in children following lead exposure. The most frequent manifestation of childhood lead toxicity is an encephalopathy associated with chronic ingestion of lead that usually presents between the ages of 1 and 3 years. Clinical manifestations include behavioral changes followed by lethargy; CONVULSIONS; HALLUCINATIONS; DELIRIUM; ATAXIA; and vomiting. Elevated intracranial pressure (HYPERTENSION, INTRACRANIAL) and CEREBRAL EDEMA may occur. (From Adams et al., Principles of Neurology, 6th ed, p1210-2)
Lead Poisoning, Nervous System, Adult
Neurologic conditions in adults associated with acute or chronic exposure to lead or any of its salts. The most common lead related neurologic syndrome in adults consists of a polyneuropathy involving motor fibers. This tends to affect distal nerves and may present as wrist drop due to RADIAL NEUROPATHY. Additional features of chronic lead exposure include ANEMIA; CONSTIPATION; colicky abdominal pain; a bluish lead line of the gums; interstitial nephritis (NEPHRITIS, INTERSTITIAL); and saturnine gout. An encephalopathy may rarely occur. (From Adams et al., Principles of Neurology, 6th ed, p1212)
Ciguatera Poisoning
Poisoning caused by ingestion of SEAFOOD containing microgram levels of CIGUATOXINS. The poisoning is characterized by gastrointestinal, neurological and cardiovascular disturbances.
Clinical Trials
Penicillamine, Low Copper Diet, and Radiation Therapy in Treating Patients With Glioblastoma
RATIONALE: Penicillamine may stop the growth of glioblastomas by stopping blood flow to the tumor. A diet low in copper may interfere with the growth of brain tumor cells. Radiation therap...
Homeopathic Preparation Plumbum Metallicum for Lead Poisoning
Saturnism, or lead poisoning, is defined by clinical symptoms (affecting primarily the nervous, hematopoietic, gastrointestinal, cardiovascular, musculoskeletal, renal and reproductive sys...
Identifying Residential Hazards Using Home Test Kits
The purpose of this project is to help families and communities identify and reduce health risks from lead, pesticides and, ultimately, other environmental hazards. We have partnered with...
Outcome Following Carbon Monoxide Poisoning in Children
Carbon monoxide poisoning is common. Many adults with CO poisoning have long-term, even permanent brain injury following poisoning. However, very little is known about the long-term outcom...
Exposure, Dose, Body Burden and Health Effects of Lead
This is a study of the effects that lead has on the health of the central nervous system (for example, memory), peripheral nervous system (for example, sensation and strength in the hands...
PubMed Articles
ABSTRACT: Background Adhesions formation is a significant postsurgical complication. At present, there is no effective method for preventing adhesions formation [1], although the barrier products such...
Lead Poisoning of a Child Associated with Use of a Cambodian Amulet --- New York City, 2009.
Lead poisoning in children is a preventable public health problem that can adversely affect the developing nervous system and result in learning and behavior problems. The most common source of exposu...
The objective of this study was to evaluate the effects of allicin, the main biologically active component of garlic clove extracts, on lead levels in different common carp tissues including liver, ki...
While aminothiols produce weak purple-colored reactions with ninhydrin, we demonstrate for the first time that this color could be intensely developed. Using a d-penicillamine paradigm, adsorption of...
ABSTRACT: BACKGROUND: Lead is a heavy metal and important environmental toxicant and nerve poison that can destruction many functions of the nervous system. Lead poisoning is a medical condition cause...
