Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03655639 |
| Other study ID # |
2017-1178 |
| Secondary ID |
U01HL133704 |
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
September 9, 2018 |
| Est. completion date |
February 16, 2026 |
Study information
| Verified date |
November 2022 |
| Source |
Ann & Robert H Lurie Children's Hospital of Chicago |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Infants who are born prematurely have immature nervous and cardiorespiratory systems. These
are systems infants use to breathe, to move oxygen throughout their bodies, and to maintain
safe and stable levels of oxygen and carbon dioxide. The goal of this study is to better
understand how these immature systems affect long term development, such as brain, heart, and
motor function (movement) with several innovative, integrated physiological measures. We hope
this will allow us to begin to find better ways to help premature infants breathe and to
optimize their development.
Description:
The broad long-term objective is to use comprehensive state-of-the-art, 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. SPECIFIC 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 weeks (wks) post-menstrual age (PMA)(up
to 24-hour recordings) and at 3 and 12 months (mos) corrected age (CA)(4-hour recordings).
Aim 1 tests the hypothesis that individual and integrated metrics of ANS function will
demonstrate maturational patterns that impart resilience or vulnerability to environmental
challenges. SPECIFIC 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
(RMSS), need for respiratory support, medications, or hospitalization, Bayley Scales of
Infant Development III (6, 12 mos), Neurological, Sensory, Motor, Developmental Assessment
(NSMDA)(3, 6, 12 mos), and early measures of evoked-auditory potentials (EAP)(28, 32, 36 wks
PMA; 3, 12 mos CA) and General Movement Assessments (GMA)(28, 32, 36 wks; 3 mos). Aim 2 tests
the hypothesis that infants demonstrating delayed ANS maturation or vulnerability to
endogenous challenges will require more respiratory interventions and will demonstrate
developmental delays in the 1st year of life. SPECIFIC 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 [1) "normal" maturation with ability to withstand
environmental perturbations; 2) "normal" maturation without ability to withstand
environmental perturbations; and 3) 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 year. This
novel approach will establish the role of autonomic neurorespiratory maturation in stability
of oxygenation throughout the 1st year of life, provide insight into BPD pathogenesis, allow
prospective identification of at-risk infants, and permit development of mechanism-specific
interventions with potential to impact thousands of families and billions in healthcare
cost/year in the U.S., alone.
In addition to lung-independent mechanisms of respiratory dysfunction, this study aims to
investigate lung-independent mechanisms of pulmonary hypertension (PH). 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, we 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 from our group and others suggest a role for Fibroblast Growth Factor 2
(FGF2) and FGF receptors 1 and 2 (FGFR1, FGFR2) signaling in the development of pulmonary
vascular remodeling in PH. Thus, by serially using sensitive echocardiographic measures of
Right Ventricular-Pulmonary Arterial (RV-PA) coupling, we can quantify hypoxic exposure and
RV-PA axis dysfunction and we will couple these clinical measurements of FGF2 signaling. We
hypothesize that recurrent hypoxic exposure of dysmature pulmonary vasculature in premature
newborns results in RV-PA axis dysfunction and pulmonary hypertension that is mediated by
FGF2 signaling and is independent of clinically apparent lung disease.
