PTGS1 Genetic Variation and Increased Risk for Persistent Pulmonary Hypertension of the Newborn (PPHN)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by Medical College of Wisconsin
Sponsor:
Information provided by (Responsible Party):
G. Ganesh Konduri, Medical College of Wisconsin
ClinicalTrials.gov Identifier:
NCT00710177
First received: July 2, 2008
Last updated: August 19, 2013
Last verified: August 2013
  Purpose

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).


Condition
Persistent Pulmonary Hypertension

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Prostaglandin G/H Synthase-1 (PTGS1) Genetic Variation and Increased Risk for Persistent Pulmonary Hypertension of the Newborn (PPHN)

Resource links provided by NLM:


Further study details as provided by Medical College of Wisconsin:

Primary Outcome Measures:
  • To determine whether or not a variation in the prostaglandin G/H Synthase-1 gene contributes to the incidence of PPHN in infants who are exposed to NSAIDs in utero. [ Time Frame: through discharge from the hospital ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

whole blood, meconium


Estimated Enrollment: 60
Study Start Date: January 2006
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
PPHN
Infants born after 34 weeks gestational age who are diagnosed with PPHN
Control
Infants born greater than 34 weeks gestational age and do not have PPHN

Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

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.

Criteria

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
  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: NCT00710177

Contacts
Contact: Ganesh Konduri, MD 414-266-6452 gkonduri@mcw.edu
Contact: Laura L Lane, BSN 414-337-7312 llane@mcw.edu

Locations
United States, Wisconsin
Children's Hospital of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Principal Investigator: Ganesh Konduri, MD         
Sponsors and Collaborators
Medical College of Wisconsin
Investigators
Principal Investigator: Ganesh Konduri, MD Medical College of Wisconsin
Study Chair: Laura Lane, BSN Medical College of Wisconsin
Study Chair: Kathleen Meskin, BSN Medical College of Wisconsin
  More Information

No publications provided

Responsible Party: G. Ganesh Konduri, Chief, Division of Neonatology, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT00710177     History of Changes
Other Study ID Numbers: CHW 06/92, GC 49
Study First Received: July 2, 2008
Last Updated: August 19, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Medical College of Wisconsin:
PPHN
PTGS1
NSAID

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Persistent Fetal Circulation Syndrome
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Infant, Newborn, Diseases

ClinicalTrials.gov processed this record on July 28, 2014