Improving Prematurity-Related Respiratory Outcomes at Vanderbilt

Preterm Birth Clinical Trial

— IMPROV  

Official title:

Improving Prematurity-Related Respiratory Outcomes at Vanderbilt: The Prematurity and Respiratory Outcomes Program (PROP)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01460576
• Other study ID #: 110833
• Secondary ID: 1U01HL101456
• Status: Completed
• Phase: N/A
• First received: October 24, 2011
• Last updated: May 2, 2017
• Start date: September 2011
• Est. completion date: December 2016

Study information

• Verified date: May 2017
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 253
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 7 Days

Eligibility

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.

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia
• Chronic Lung Disease of Prematurity
• Lung Diseases
• Premature Birth
• Preterm Birth

Locations

Country	Name	City	State
United States	Jackson Madison County General Hospital	Jackson	Tennessee
United States	Monroe Carell Jr. Children's Hospital at Vanderbilt	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Ananthakrishnan M, Barr FE, Summar ML, Smith HA, Kaplowitz M, Cunningham G, Magarik J, Zhang Y, Fike CD. L-Citrulline ameliorates chronic hypoxia-induced pulmonary hypertension in newborn piglets. Am J Physiol Lung Cell Mol Physiol. 2009 Sep;297(3):L506-11. doi: 10.1152/ajplung.00017.2009. Epub 2009 Jul 17. — View Citation

Fike CD, Sidoryk-Wegrzynowicz M, Aschner M, Summar M, Prince LS, Cunningham G, Kaplowitz M, Zhang Y, Aschner JL. Prolonged hypoxia augments L-citrulline transport by system A in the newborn piglet pulmonary circulation. Cardiovasc Res. 2012 Aug 1;95(3):375-84. doi: 10.1093/cvr/cvs186. Epub 2012 Jun 6. — View Citation

Vadivel A, Aschner JL, Rey-Parra GJ, Magarik J, Zeng H, Summar M, Eaton F, Thébaud B. L-citrulline attenuates arrested alveolar growth and pulmonary hypertension in oxygen-induced lung injury in newborn rats. Pediatr Res. 2010 Dec;68(6):519-25. doi: 10.1203/PDR.0b013e3181f90278. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Respiratory morbidity	Need for oxygen, respiratory medications, hospital admissions for respiratory disease or a positive response in at least 1 of 4 morbidity domains during at least 2 separate parental interviews.	one year corrected age
Secondary	bronchopulmonary dysplasia	need for oxygen at 36 weeks based on a room air challenge	36 weeks corrected age