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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 : May 15, 2020
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

Study Description
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Brief 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.

Condition or disease
Premature Birth

Detailed 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.

Study Design
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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 : December 31, 2020
Estimated Study Completion Date : December 31, 2020
Groups and Cohorts
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Group/Cohort
Premature Birth
Premature babies born under 29 weeks gestational age, admitted into the neonatal intensive care unit within 7 days of life.


Outcome Measures
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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

Eligibility Criteria
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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 than 1 week of age

Exclusion Criteria:

  • known congenital anomalies
  • imminent death
  • factors that preclude reliable follow-up
Contacts and Locations
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Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

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
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Contact: Aaron Hamvas 312-227-1400 ahamvas@luriechildrens.org
Contact: Debra Weese-Mayer 312-227-3300 dweese-mayer@luriechildrens.org

Locations
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United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Erin Lonergan, BHS    312-227-1000 ext 3315    Ersmith@luriechildrens.org   
Northwestern Memorial Hospital Recruiting
Chicago, Illinois, United States, 60611
Contact: Erin Lonergan, BHS    312-227-1000 ext 3315    Ersmith@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
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Principal Investigator: Aaron Hamvas Ann & Robert H Lurie Children's Hospital of Chicago
More Information
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Responsible Party: Ann & Robert H Lurie Children's Hospital of Chicago
ClinicalTrials.gov Identifier: NCT03655639    
Other Study ID Numbers: 2017-1178
U01HL133704 ( U.S. NIH Grant/Contract )
First Posted: August 31, 2018    Key Record Dates
Last Update Posted: May 15, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Premature Birth
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications