Functional and Lymphocytic Markers of Respiratory Morbidity in Hyperoxic Preemies

January 7, 2020 updated by: Gloria Pryhuber, University of Rochester

Prematurity and Respiratory Outcome Program: Single Center Study of Functional and Lymphocytic Markers of Respiratory Morbidity in Hyperoxic Preemies

This is an observational study that proposes to collect clinical, physiological, cellular and molecular information in an attempt to identify a set of factors that may predict the risk for persistent lung disease in babies born prematurely.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

Approximately 550,000 babies born prematurely each year in the United States suffer from birth at a time in development when the respiratory tract and immune system would normally be protected and maintained in a naïve state. This project is a component of the NIH Prematurity and Respiratory Outcomes Program (PROP) whose goals are the identification of disease mechanisms and biomarkers to stratify premature infants, at the time of discharge, for their risk of subsequent pulmonary morbidity. This Clinical Research Center (CRC) project will investigate prematurity-dependent alterations in cellular innate and adaptive immune systems resulting in increased susceptibility to respiratory infections and environmental irritants, and leading to respiratory morbidity in the first year of life. Prior studies have established developmental (maturity) and disease-related changes in circulating and pulmonary lymphocyte populations but a comprehensive assessment of their relationship to disease risk/outcome has not been undertaken. We hypothesize that cellular and molecular immuno-maturity is altered due to intrinsic and extrinsic factors presented by premature birth in such a way as to reduce resistance to viral infections and to promote cytotoxic damage to the lung. We will evaluate immunologic maturity by comprehensively phenotyping lymphocyte populations in peripheral blood sampled at premature delivery, at the time of discharge from the hospital and at twelve months corrected age. The lymphocytic phenotype will be analyzed particularly in the context of gestational age and maternal-fetal stressors capable of modulating oxidative stress (oxygen exposure, infection and environmental tobacco smoke exposure). Additionally, we will assess changes in the molecular phenotype of isolated CD8 lymphocytes, a cell type preferentially recruited to the lungs of premature infants and capable of contributing to disease pathogenesis, by genome-wide expression profiling, in order to uncover novel disease pathways and define a gene expression signature associated with disease risk. Finally, we propose to build a statistical model, using cellular and molecular phenotypes and additional clinical variables, for stratifying risk of lung morbidity within the first year of life.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
277

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Buffalo, New York, United States, 14222
        • Women and Children's Hospital of Buffalo
      • Rochester, New York, United States, 14642
        • University of Rochester Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 1 week (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Eligible subjects are limited to patients born at the Golisano Children's Hospital at the University of Rochester Medical Center and at Women's and Children's Hospital, University at Buffalo. All admissions to the participating Neonatal Intensive Care Units will be screened for eligibility.

Description

Inclusion Criteria:

  1. Premature infants born at gestational age 24 0/7 to 35 6/7 week and admitted to the Neonatal Intensive Care Unit or normal newborn nursery at URMC or UB
  2. Healthy term infants 37 0/7 to 41 6/7 recruited from the birthing centers or Ob/Gyn floors (3-1200 at URMC) prior to discharge
  3. Infants who are less than or equal to 7 days old

Exclusion Criteria:

  1. The infant is not considered to be viable (therapies limited due to futility decision made by clinical care team)
  2. Congenital heart disease (not including PDA and hemodynamically insignificant VSD or ASD)
  3. Structural abnormalities of the upper airway, lungs or chest wall
  4. Other congenital malformations or syndromes that adversely affect life expectancy or cardio-pulmonary development
  5. Family is unlikely to be available for long-term follow-up as determined by the site investigators dependent on the distance of the infant's residence from the follow-up center and/or family plans to move out of the region
  6. Family does not speak or understand English

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Premature Infant
Infants born 23 0/7 weeks gestation to 35 6/7 weeks gestation.
Healthy Full Term Infants
Infants born between 37 0/7 weeks gestation to 41 6/7 weeks gestation.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Symptomatic Respiratory Disease (SRD)
Time Frame: Assessed every three months until 1 year corrected gestational age
The primary goal of the PROP studies (single center and multicenter protocols) 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 up to 1 year corrected age. We propose a composite primary outcome of SRD that is based on serial parental reports of respiratory symptoms, medications, hospitalizations and dependence on technology during the first year of life.
Assessed every three months until 1 year corrected gestational age

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Assessment of T lymphocyte numbers, subsets (CD4, CD8) and functional phenotype determined by flow cytometry.
Time Frame: Measured and compared at birth, at term corrected gestational age and at 1 year corrected gestational age
Assessment of T lymphocyte numbers, subsets (CD4, CD8) and functional phenotype including characteristics of effector and memory function, and intracellular cytokine production in response to in vitro T cell receptor nonspecific and specific stimulation
Measured and compared at birth, at term corrected gestational age and at 1 year corrected gestational age
Measure of severity of lung disease at 40 +/- 5 weeks corrected gestational age
Time Frame: From birth at premature gestational age to at 40 +/- 5 weeks corrected gestational age
Severity of lung disease will be assessed by length of time on mechanical ventilation, length of time on oxygen, oxygen requirement at 36 weeks corrected gestational age, need for pulmonary medications at determined at hospital discharge, or at 40 +/- 5 weeks corrected gestational age.
From birth at premature gestational age to at 40 +/- 5 weeks corrected gestational age
Statistical correlation of CD4 and CD8 lymphocyte function with severity and persistence of lung disease.
Time Frame: At at 40 +/- 5 weeks corrected gestational age and at one year of age
The severity of lung disease prior to first hospital discharge and the persistence and severity of SRD in the first year of life will be compared with the T cell lymphocyte phenotypes at birth, at hospital discharge and at one year of life. Specifically, at minimum, the ability of T lymphocytes at rest and after stimulation to produce interferon gamma at the test time points will be compared with the history of lung disease. The intent is to identify biomarkers and to suggest immune-mediated mechanisms for lung disease in preterm infants
At at 40 +/- 5 weeks corrected gestational age and at one year of age
Gene expression analysis of CD8 cells collected by FACS from preterm infants nearing discharge
Time Frame: At 40 +/- 5 weeks corrected gestational age
Patterns of gene expression identified in isolated and sorted CD8 T cells from preterm infants just prior to discharge from the neonatal intensive care unit will be identified and compared to the severity and persistence of symptomatic respiratory disease (SRD) over the first year of life.
At 40 +/- 5 weeks corrected gestational age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Rochester

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)
National Institutes of Health (NIH)
University at Buffalo

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Gloria Pryhuber, MD, University of Rochester
  • Principal Investigator: Rita Ryan, MD, University at Buffalo
  • Principal Investigator: Thomas Mariani, PhD, University of Rochester

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 14, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 24, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 30, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 13, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 7, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 37933
  • U01HL101813 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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