Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Local Version of the Multi-center PREVENT Study Evaluating Cardio-respiratory Instability in Premature Infants

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03655639
Recruitment Status : Recruiting
First Posted : August 31, 2018
Last Update Posted : August 31, 2018
Sponsor:
Collaborators:
Northwestern Memorial Hospital
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Ann & Robert H Lurie Children's Hospital of Chicago

Brief Summary:
Studies have shown that premature infants encounter daily exposure to low oxygen (hypoxia) and elevated carbon dioxide (hypercapnia) scenarios that challenge their overall cardiovascular-respiratory stability. Generally, when these states are encountered, the infant's system automatically adjusts to compensate and no intervention is needed. In this proposed study, staff will be replicating these conditions in a brief, controlled manner to determine an infant's ability to compensate and the degree of autonomic nervous system maturity. The trajectory of this maturation will be related to neurodevelopmental outcomes at 1 year of age.

Condition or disease
Premature Birth

Detailed Description:
The broad long-term objective is to use comprehensive state-of-the high-fidelity monitoring to investigate physiological biomarkers of autonomic neurorespiratory maturation with integrated analysis of autonomic nervous system (ANS) responses in preterm infants, and to evaluate their role in ventilatory instability, bronchopulmonary dysplasia (BPD), and co-morbidities including neurodevelopment in the 1st year of life. Aim 1 will establish the spectrum and developmental trajectory of ANS maturation/function using high-resolution physiologic recordings of ventilatory, cardiovascular, and cerebrovascular measures during typical daily activity (28, 32 and 36 wks gestational age (GA)(23-hour recordings); 3 and 12 mos corrected age (CA)(4-hour recordings)) and physiologic response testing (brief hyperoxic and hypercarbic testing) to evaluate peripheral and central chemoreceptors responses and maturation and to evaluate latent autonomic and respiratory instability (32 and 36 wks; 3 and 12 mos). Aim 1 tests the hypothesis that individual and integrated metrics of ANS function will demonstrate maturational patterns that impart resilience or vulnerability to environmental and exogenous challenges. Aim 2 will determine respiratory and neurodevelopmental morbidity throughout the 1st year of life using clinically applicable outcome measures and associate morbidity with ANS development and function using a Respiratory Morbidity Severity Score, need for respiratory support, medications, or hospitalization, Bayley Scales of Infant Development III (6, 12 mos), Neurological, Sensory, Motor, Developmental Assessment (3, 6, 12 mos), and early measures of evoked-auditory potentials (EAP) and General Movement Assessments (GMA)(28, 32, 36 wks; 3 months). Aim 2 tests the hypothesis that infants demonstrating delayed ANS maturation or vulnerability to endogenous or exogenous challenges will require more respiratory interventions and will demonstrate developmental delays in the 1st year of life. Aim 3 will determine endotypes of autonomic neurorespiratory stability and maturation through trajectory analysis and integrated physiological modeling. Aim 3 tests the hypothesis that trajectory analysis will reveal 3 autonomic maturation patterns ("normal" maturation with ability to withstand environmental perturbations; "normal" maturation without ability to withstand environmental perturbations; delayed or disordered maturation with inability to maintain physiologic stability in absence of environmental perturbations) that will be associated with severity of respiratory morbidity and neuromotor impairment at 1 yr. In addition to lung-independent mechanisms of respiratory dysfunction, this study aims to investigate lung-independent mechanisms pulmonary hypertension (PH) in premature babies. Typically thought to be a secondary effect of primary lung structural development and/or hypoxia, up to 40% of infants with chronic respiratory dysfunction develop pulmonary hypertension (PH) and increased risk for mortality. However, the investigators and others found that 10-30% of premature infants who develop PH did not have clinical evidence of respiratory dysfunction, suggesting pulmonary vascular mechanisms that are independent of clinically apparent respiratory disease. Multiple molecular mechanisms are postulated by which hypoxia results in PH, but preliminary data suggest a role for Fibroblast Growth Factor 2 (FGF2) and Granulocyte-Colony Stimulating Factor (G-CSF) signaling in the development of pulmonary vascular remodeling in PH. Thus, by serially using sensitive echocardiographic measures of Right Ventricular-Pulmonary Circulation (RV-PC) coupling, the investigators can quantify hypoxic exposure and RV-PC axis dysfunction and the investigators will couple these clinical measurements with mechanistic studies of FGF2 signaling. The investigators hypothesize that recurrent hypoxic exposure of dysmature pulmonary vasculature in premature newborns results in RV-PC axis dysfunction and pulmonary hypertension that is mediated by FGF2 and G-CSF independent of clinically apparent lung disease.

Layout table for study information
Study Type : Observational
Estimated Enrollment : 120 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Evaluating Cardiorespiratory Development in Premature Babies
Actual Study Start Date : June 1, 2018
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : June 30, 2020

Group/Cohort
Premature Birth
Premature babies born under 29 weeks gestational age, admitted into the neonatal intensive care unit within 7 days of life.



Primary Outcome Measures :
  1. Change in cardiorespiratory coupling between 28 weeks postmenstrual age and 1 year [ Time Frame: 1 year ]
    Average cross-spectral coherence between heart rate and respiratory rate summed within the high frequency band (above 0.15 Hz; ratiometric units). Higher coherence indicates better coupling.


Secondary Outcome Measures :
  1. Neurodevelopmental outcomes as measured with the Neurological, Sensory, Motor, Developmental Assessment (NSMDA) functional grade [ Time Frame: 1 year ]
    6 subtests are scored individually (1-5 with 1 being normal, 5 with profound disability) and added together - normal 6-8, 9-11 minimal dysfunction, 12-14 mild problems, 16-19 moderate disability, 20-24 severe disability and 25-30 multiple, severe or profound disabilities.


Other Outcome Measures:
  1. Change in right ventricle-pulmonary circulation (RV-PC) axis function between 32 and 36 weeks postmenstrual age [ Time Frame: 36 weeks postmenstrual age ]
    echocardiographic measurements of pulmonary artery acceleration time (PAAT, milliseconds), where values less than 43 msec are indicative of RV-PC axis dysfunction

  2. Changes in circulating levels of fibroblast growth factor 2 (FGF2) and granulocyte macrophage colony stimulating factor (G-CSF) between 32 and 36 weeks postmenstrual age [ Time Frame: 36 weeks postmenstrual age ]
    comparison of FGF2 and G-CSF levels as measured by immunoassay between infants with and without RV-PC axis dysfunction


Biospecimen Retention:   Samples With DNA
Buccal DNA swab


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   24 Weeks to 29 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Premature babies born under 29 weeks of gestational age, who are admitted into the neonatal intensive care unit within a week of birth.
Criteria

Inclusion Criteria:

  • birth between 24 and 29 weeks of gestation
  • less that 1 week of age

Exclusion Criteria:

  • known congenital anomalies
  • imminent death
  • factors that preclude reliable follow-up

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): NCT03655639


Contacts
Layout table for location contacts
Contact: Aaron Hamvas 312-227-1400 ahamvas@luriechildrens.org
Contact: Debra Weese-Mayer 312-227-3300 dweese-mayer@luriechildrens.org

Locations
Layout table for location information
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Summer R Fair, BS    312-227-1000 ext 3315    srfair@luriechildrens.org   
Northwestern Memorial Hospital Recruiting
Chicago, Illinois, United States, 60611
Contact: Summer R Fair, BS    312-227-1000 ext 3315    srfair@luriechildrens.org   
Sponsors and Collaborators
Ann & Robert H Lurie Children's Hospital of Chicago
Northwestern Memorial Hospital
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Layout table for investigator information
Principal Investigator: Aaron Hamvas Ann & Robert H Lurie Children's Hospital of Chicago

Layout table for additonal information
Responsible Party: Ann & Robert H Lurie Children's Hospital of Chicago
ClinicalTrials.gov Identifier: NCT03655639     History of Changes
Other Study ID Numbers: 2017-1178
U01HL133704 ( U.S. NIH Grant/Contract )
First Posted: August 31, 2018    Key Record Dates
Last Update Posted: August 31, 2018
Last Verified: August 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Premature Birth
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications