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Sponsored by: |
Washington University School of Medicine |
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Information provided by: | Washington University School of Medicine |
ClinicalTrials.gov Identifier: | NCT00828243 |
Inherited deficiencies in any one of 3 genes (surfactant protein B, surfactant protein C, and ATP-binding cassette transporter A3) can cause neonatal respiratory distress syndrome by disrupting metabolism of the pulmonary surfactant. The investigators will use state of the art methods to link specific changes in the genetic code of each of these genes with disruption of discrete steps in the metabolism of the pulmonary surfactant in human newborn infants. These studies will lead to improved diagnostic capabilities and suggest novel strategies to correct surfactant deficiency in newborn infants.
Condition |
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Respiratory Distress Syndrome, Newborn |
Study Type: | Observational |
Study Design: | Case Control, Prospective |
Official Title: | Genetic Regulation of Surfactant Deficiency in Human Newborn Infants |
DNA samples and tracheal aspirate samples will be retained on each study participant.
Estimated Enrollment: | 730 |
Study Start Date: | November 2007 |
Estimated Study Completion Date: | March 2012 |
Estimated Primary Completion Date: | March 2012 (Final data collection date for primary outcome measure) |
Groups/Cohorts |
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Case-control
Newborn infants with and without neonatal respiratory distress syndrome
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Case
Infants with varying severity of neonatal respiratory distress
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Genetic regulation of neonatal pulmonary surfactant deficiency has been suggested by studies of gender, genetic linkage, recurrent familial cases, targeted gene ablation in murine lineages, and by racial disparity in risk of neonatal respiratory distress syndrome. Successful fetal-neonatal pulmonary transition requires production of the pulmonary surfactant, a phospholipid-protein film that lines alveoli and maintains alveolar patency at end expiration. Our goal is to understand the genetic mechanisms that disrupt pulmonary surfactant metabolism and cause neonatal respiratory distress syndrome. Studies in human newborn infants have demonstrated that 3 genes are critical for surfactant metabolism: surfactant protein B (SFTPB), surfactant protein C (SFTPC), and an ATP-binding cassette transporter, ABCA3 (ABCA3). To understand genetic regulatory mechanisms, we will investigate the contribution of variation in each of these genes to risk of neonatal respiratory distress syndrome by testing the hypothesis that genetic variants in the SFTPB, SFTPC, and ABCA3 disrupt pulmonary surfactant metabolism. Using high throughput automated sequencing to genotype, multidimensional protein identification technology to assess quantitative and qualitative differences in surfactant protein B and C expression, in vivo metabolic labeling with stable isotopically labeled precursors to estimate surfactant protein B and C and phospholipid metabolic rates, and cohort sizes that provide statistical power (0.8), we will use race-specific, severity-stratified case-control (N=480) and case comparison (N=250) designs to understand genetically regulated, metabolic mechanisms that cause surfactant deficiency by disrupting expression or altering processing of surfactant proteins B or C or by disrupting surfactant phospholipid composition in human newborn infants. Improved understanding of genetic regulation of surfactant deficiency will suggest novel diagnostic strategies to identify and categorize high risk infants and therapeutic strategies that target discrete steps in pulmonary surfactant metabolism to improve outcomes of infants with neonatal respiratory distress syndrome.
Ages Eligible for Study: | up to 1 Year |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Sampling Method: | Non-Probability Sample |
The study population includes infants with and without neonatal respiratory distress syndrome (N=480) and infants with varying severity of neonatal respiratory distress syndrome (N=250).
Inclusion Criteria:
Exclusion Criteria:
Contact: F. Sessions Cole, M.D. | 314-454-6148 | cole@kids.wustl.edu |
Contact: Aaron Hamvas, M.D. | 314-454-6148 | hamvas@kids.wustl.edu |
United States, Missouri | |
St. Louis Children's Hospital | Recruiting |
St. Louis, Missouri, United States, 63110 | |
Contact: F. Sessions Cole, M.D. 314-454-6148 cole@kids.wustl.edu | |
Contact: Aaron Hamvas, M.D. 314-454-6148 hamvas@kids.wustl.edu | |
Principal Investigator: F. Sessions Cole, M.D. |
Principal Investigator: | F. Sessions Cole, M.D. | Washington University School of Medicine |
Responsible Party: | Washington University ( F. Sessions Cole, M.D. ) |
Study ID Numbers: | 07-0156, RO1 HL082747 |
Study First Received: | January 22, 2009 |
Last Updated: | January 22, 2009 |
ClinicalTrials.gov Identifier: | NCT00828243 History of Changes |
Health Authority: | United States: Federal Government; United States: Food and Drug Administration |
Pulmonary surfactants Pulmonary surfactant associated protein B Pulmonary surfactant associated protein C ATP-binding cassette protein sub member family A3 |
Respiratory Distress Syndrome, Adult Respiration Disorders Respiratory Distress Syndrome, Newborn Acute Respiratory Distress Syndrome Infant, Premature, Diseases Pulmonary Surfactant-Associated Proteins Respiratory Tract Diseases |
Protein C Lung Diseases Infant, Newborn, Diseases Pulmonary Surfactant-Associated Protein B Pulmonary Surfactant-Associated Protein C Pulmonary Surfactants |
Respiratory System Agents Respiratory Distress Syndrome, Adult Respiration Disorders Respiratory Distress Syndrome, Newborn Infant, Premature, Diseases Pulmonary Surfactant-Associated Proteins Pharmacologic Actions |
Respiratory Tract Diseases Lung Diseases Therapeutic Uses Infant, Newborn, Diseases Pulmonary Surfactant-Associated Protein B Pulmonary Surfactant-Associated Protein C Pulmonary Surfactants |