View Clinical Trial (Medical Research Study)
Prostaglandin G/H Synthase-1 (PTGS1) Genetic Variation and Increased Risk for Persistent Pulmonary Hypertension of the Newborn (PPHN)
| City: |
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Milwaukee |
| State: |
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Wisconsin |
| Zip Code: |
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53226 |
| Conditions: |
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Persistent Pulmonary Hypertension |
| Purpose: |
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The purpose of this study is to determine if normally occurring variations in a specific
gene called PTGS-1 are associated with an increased risk of narrowing of the ductus
arteriosus from exposure to over-the-counter pain medicines (NSAIDs).
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| Study Summary: |
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Persistent pulmonary hypertension of the newborn (PPHN) occurs when the pulmonary vascular
resistance fails to decrease at birth during the transition to postnatal life. The affected
infants have severe hypoxemia, a 10% risk of mortality, and among survivors, a 30% incidence
of long term neurodevelopmental and hearing deficits. The etiology of PPHN in the majority
of affected infants remains unknown. Although constriction of fetal ductus arteriosus in
response to maternal intake of non-steroidal anti-inflammatory drugs (NSAID) has been
implicated in PPHN case reports, our laboratory was the first to provide objective evidence
for such an association. Nearly 87% of infants with PPHN were exposed to NSAID in utero.
Yet 25% of control infants also were exposed without developing PPHN. The basis for the
biological susceptibility of some neonates to in utero NSAID exposure remains poorly
understood. The hypothesis of this proposal is that PTGS1 genetic variation is associated
with increased susceptibility to ductal constriction from in utero NSAID exposure and an
increased risk of PPHN. This hypothesis will be tested through the following specific aims:
Determine the incidence of PTGS1 sequence variants in PPHN patients versus matched controls.
PTGS1 sequence will include all 11 exons, a minimum of 100 bp of exon flanking sequences,
and 1 kbp of upstream regulatory information. Cycle sequencing will be performed followed
by analysis using capillary electrophoresis. Differences in the frequency of sequence
variants will be determined using Fisher's exact test. The study will also quantify NSAID
exposure in meconium samples using a previously established GC/MS assay and correlate
exposure levels to both the incidence of PPHN and the presence or absence of PTGS1 sequence
variants using regression analysis. Benefits include the ability to predict risk for PPHN
based on PTGS1 sequence and avoidance of such risk in the future, thereby reducing patient
morbidity and mortality.
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| Criteria: |
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Inclusion Criteria:
- Infants born greater than or equal to 34 weeks gestational age diagnosed with PPHN
and normal, healthy infants born greater than or equal to 34 weeks gestational age.
Exclusion Criteria:
- Patients will be excluded if they are diagnosed with lethal congenital anomalies
- structural congenital heart disease except presence of patent ductus arteriosus (PDA)
or patent foramen ovale
- structural gastrointestinal tract abnormality that could interfere with meconium
passage
- congenital anomalies such as diaphragmatic hernia, Potter's syndrome, or pulmonary
hypoplasia
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| NCT ID: |
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NCT00710177 |
| Primary Contact: |
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Principal Investigator
Ganesh Konduri, MD
Medical College of Wisconsin
Ganesh Konduri, MD
Phone: 414-266-6452
Email: gkonduri@mcw.edu
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| Backup Contact: |
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Email: llane@mcw.edu
Laura L Lane, BSN
Phone: 414-337-7312
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| Location Contact: |
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Milwaukee, Wisconsin 53226
United States
There is no listed contact information for this specific location.
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 25, 2013 |
| Modifications to this listing: |
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