Brief Title
Improving Prematurity-Related Respiratory Outcomes at Vanderbilt
Official Title
Improving Prematurity-Related Respiratory Outcomes at Vanderbilt: The Prematurity and Respiratory Outcomes Program (PROP)
Brief Summary
The goal of IMPROV is to identify molecular mechanisms that contribute to lung injury and
long-term breathing problems in preterm infants by investigating two interrelated biochemical
pathways: the urea cycle-nitric oxide pathway and the glutathione pathway. The investigators
hypothesize that prematurity-related limitations in the function of these important
biochemical pathways contribute to respiratory disease risk over the first year of life.
Detailed Description
The primary goal of the IMPROV/PROP study is to identify biomarkers (biochemical,
physiological and genetic) and clinical variables that are associated with and thus
potentially predictive of pulmonary status in preterm infants at 1 year corrected age. IMPROV
will test the hypothesis that biochemical immaturity and functional genetic variation in the
urea cycle-nitric oxide (UC-NO) and glutathione (GSH) pathways influence the development and
severity of bronchopulmonary dysplasia (BPD), a form of chronic lung disease that affects
more than 10,000 premature infants each year in the US. IMPROV will also test the hypothesis
that the duration and degree of NO insufficiency and free radical excess predicts BPD
severity and correlates with persistence of lung problems after NICU discharge. Our
hypothesis implicates (a) an immature liver and gastrointestinal ability to make citrulline
and GSH, (b) inadequacy of nutritional amino acid substrate and (c) common genetic variations
in the UC-NO and the GSH pathways in the pathogenesis of BPD. These factors limit the ability
of the anatomically and functionally immature lung to respond to the physiologic and
environmental stress of preterm birth. As part of the PROP multi-center study, novel
approaches to characterizing lung status with non-invasive respiratory measures prior to NICU
discharge will be employed. A composite primary outcome of morbidity that is based on serial
parental reports of respiratory symptoms, medications, hospitalizations and dependence on
technology during the first year of life has been developed.
Study Type
Observational
Primary Outcome
Respiratory morbidity
Secondary Outcome
bronchopulmonary dysplasia
Condition
Preterm Birth
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Estimated Enrollment
253
Start Date
September 2011
Completion Date
December 2016
Primary Completion Date
December 2016
Eligibility Criteria
Inclusion Criteria:
- Infants who are less than or equal to 7 days old;
- Gestational Age (GA) between 23 weeks and 0/7 days and 28 weeks and 6/7 days
Exclusion Criteria:
- The infant is not considered to be viable (decision made not to provide life-saving
therapies);
- Congenital heart disease (not including PDA and hemodynamically insignificant VSD or
ASD);
- Structural abnormalities of the upper airway, lungs or chest wall;
- Other congenital malformations or syndromes that adversely affect life expectancy or
cardio-pulmonary development;
- Family is unlikely to be available for long-term follow-up.
Gender
All
Ages
N/A - 7 Days
Accepts Healthy Volunteers
No
Contacts
Judy L. Aschner, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01460576
Organization ID
110833
Secondary IDs
1U01HL101456
Responsible Party
Principal Investigator
Study Sponsor
Vanderbilt University Medical Center
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Study Sponsor
Judy L. Aschner, MD, Principal Investigator, Albert Einstein College of Medicine; Vanderbilt University School of Medicine
Verification Date
May 2017