A Phase 2/3 Trial of d-Penicillamine Chelation in Lead-Poisoned Children
Penicillamine Chelation for Children With Lead Poisoning
Sponsors
Source
FDA Office of Orphan Products Development
Oversight Info
Has Dmc
Yes
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.
Overall Status
Withdrawn
Start Date
2007-09-01
Completion Date
N/A
Primary Completion Date
N/A
Phase
Phase 2/Phase 3
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
|
• 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
Measure |
Time Frame |
|
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 |
Conditions
Intervention
Intervention Type
Device
Intervention Name
Description
d-penicillamine twice daily, 15 mg/kg/day, for 6 weeks
Arm Group Label
1
Intervention Type
Drug
Intervention Name
Description
placebo with same characteristics as drug
Arm Group Label
2
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
Gender
All
Minimum Age
6 Months
Maximum Age
16 Years
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
|
Michael W Shannon, MD |
Study Director |
Boston Children’s Hospital |
Location
Facility |
|
Children's Hospital Boston Boston Massachusetts 02115 United States |
Location Countries
Country
United States
Verification Date
2007-12-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Name Title
Michael Shannon, MD
Organization
Children's Hospital Boston
Keywords
Has Expanded Access
No
Condition Browse
Secondary Id
1R01FD003361-01A1
Number Of Arms
2
Intervention Browse
Mesh Term
Penicillamine
Arm Group
Arm Group Label
1
Arm Group Type
Experimental
Description
This group will receive d-penicillamine for 6 weeks
Arm Group Label
2
Arm Group Type
Placebo Comparator
Description
This group will receive placebo for 6 weeks
Firstreceived Results Date
N/A
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Study First Submitted
November 1, 2007
Study First Submitted Qc
November 1, 2007
Study First Posted
November 2, 2007
Last Update Submitted
March 24, 2015
Last Update Submitted Qc
March 24, 2015
Last Update Posted
March 26, 2015
ClinicalTrials.gov processed this data on August 27, 2018
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.