Improving Prematurity-Related Respiratory Outcomes at Vanderbilt (IMPROV)

• ClinicalTrials.gov Identifier: NCT01460576
• Recruitment Status: Completed
• First Posted: October 27, 2011
• Last Update Posted: May 5, 2017
• Sponsor: Vanderbilt University Medical Center
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Paul Moore, Vanderbilt University Medical Center

Study Description

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.

Condition or disease
Preterm Birth; Bronchopulmonary Dysplasia; Chronic Lung Disease of Prematurity

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 Design

• Study Type: Observational
• Actual Enrollment: 253 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Improving Prematurity-Related Respiratory Outcomes at Vanderbilt: The Prematurity and Respiratory Outcomes Program (PROP)
• Study Start Date: September 2011
• Actual Primary Completion Date: December 2016
• Actual Study Completion Date: December 2016

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Respiratory morbidity [ Time Frame: one year corrected age ]
   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.

Secondary Outcome Measures :

1. bronchopulmonary dysplasia [ Time Frame: 36 weeks corrected age ]
   need for oxygen at 36 weeks based on a room air challenge

Biospecimen Retention:   Samples With DNA

saliva for DNA, plasma, red blood cells, urine and tracheal aspirates

Eligibility Criteria

• Ages Eligible for Study: up to 7 Days (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Infants admitted to the Neonatal Intensive Care Unit who are < 29 weeks gestational age

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.

Contacts and Locations

Locations

United States, Tennessee

Jackson Madison County General Hospital

Jackson, Tennessee, United States, 38301

Monroe Carell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, United States, 37232

Sponsors and Collaborators

Vanderbilt University Medical Center

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Judy L. Aschner, MD; Albert Einstein College of Medicine; Vanderbilt University School of Medicine

More Information

Publications:

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.

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.

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.

• Responsible Party: Paul Moore, Asscoc. Professor, Vanderbilt University Medical Center
• ClinicalTrials.gov Identifier: NCT01460576
• Other Study ID Numbers: 110833; 1U01HL101456 ( U.S. NIH Grant/Contract )
• First Posted: October 27, 2011
• Last Update Posted: May 5, 2017
• Last Verified: May 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Paul Moore, Vanderbilt University Medical Center:

prematurity; respiratory disease; bronchopulmonary dysplasia

Additional relevant MeSH terms:

Lung Diseases; Bronchopulmonary Dysplasia; Premature Birth; Respiratory Tract Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Ventilator-Induced Lung Injury; Lung Injury; Infant, Premature, Diseases; Infant, Newborn, Diseases