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

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ClinicalTrials.gov Identifier: NCT00710177
Recruitment Status : Recruiting
First Posted : July 4, 2008
Last Update Posted : January 18, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:
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 or disease
Persistent Pulmonary Hypertension of the Newborn

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.

Study Design

Study Type : Observational
Estimated Enrollment : 120 participants
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)
Study Start Date : January 2006
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Groups and Cohorts

Infants born at >= 34 weeks who are diagnosed with clinical and/or echocardiographic evidence of PPHN
Randomly selected, normal healthy infants born at >= 34 weeks gestational age and do not have PPHN

Outcome Measures

Primary Outcome Measures :
  1. 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: participants will be followed for the duration of hospital stay, an expected average of 3 weeks ]

Biospecimen Retention:   Samples With DNA
whole blood, meconium

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 12 Months   (Child)
Sexes Eligible for Study:   All
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.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00710177

Contact: G. Ganesh Konduri, MD 414-266-6820 gkonduri@mcw.edu
Contact: Laura L Lane, BSN 414-337-7312 llane@mcw.edu

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
Principal Investigator: G. Ganesh Konduri, MD Medical College of Wisconsin
More Information

Responsible Party: G. Ganesh Konduri, Chair, Division of Neonatology, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT00710177     History of Changes
Other Study ID Numbers: CHW 06/02, GC 49
First Posted: July 4, 2008    Key Record Dates
Last Update Posted: January 18, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by G. Ganesh Konduri, Medical College of Wisconsin:

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