PrematurityNCT01607216
Functional and Lymphocytic Markers of Respiratory Morbidity in Hyperoxic Preemies
An observational study of Prematurity and Symptomatic Respiratory Disease, run by University of Rochester at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages Up to 7 days
- Conditions the study is for
- Prematurity, Symptomatic Respiratory Disease, Bronchopulmonary Dysplasia
- How many people
- 277 participants
- Where
- 2 sitesUnited States
- Study dates
- Aug 2011to Jul 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 7 days
- All sexes
- No healthy volunteers
- Child
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.
Who may be able to join
- 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
- 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
- Infants who are less than or equal to 7 days old
Who cannot join
- The infant is not considered to be viable (therapies limited due to futility decision made by clinical care team)
- 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 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
- Family does not speak or understand English
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Women and Children's Hospital of Buffalo
Buffalo, New York, 14222
University of Rochester Medical Center
Rochester, New York, 14642
About this study
Official title: 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.
Read the 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.
- Keywords
- Prematurity, Respiratory Illness, Lung Function, Lung Disease
- Medical subject headings
- Premature Birth, Bronchopulmonary Dysplasia, Lung Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
Symptomatic Respiratory Disease (SRD)
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.
Measured: Assessed every three months until 1 year corrected gestational age
Secondary outcomes (4)
Assessment of T lymphocyte numbers, subsets (CD4, CD8) and functional phenotype determined by flow cytometry.
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: 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
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.
Measured: 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.
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
Measured: 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
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.
Measured: At 40 +/- 5 weeks corrected gestational age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2012 (estimated)
- Study startAug 2011
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for PrematurityStudies of the same condition, open and under way.
- More trials run by University of RochesterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 277 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), University at Buffalo
- Responsible party
- Principal investigator, Gloria Pryhuber, University of Rochester
- Investigators
- Gloria Pryhuber, MD, Principal investigator, University of RochesterRita Ryan, MD, Principal investigator, University at BuffaloThomas Mariani, PhD, Principal investigator, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01607216
- Sponsor's protocol ID
- 37933
- Other IDs
- U01HL101813
- Status last verified
- Jan 2020
- First submitted
- 14 Mar 2012
- Last updated
- 13 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Maitre NL, Ballard RA, Ellenberg JH, Davis SD, Greenberg JM, Hamvas A, Pryhuber GS; Prematurity and Respiratory Outcomes Program. Respiratory consequences of prematurity: evolution of a diagnosis and development of a comprehensive approach. J Perinatol. 2015 May;35(5):313-321. doi: 10.1038/jp.2015.19. Epub 2015 Mar 26.
PubMed 25811285Pryhuber GS, Maitre NL, Ballard RA, Cifelli D, Davis SD, Ellenberg JH, Greenberg JM, Kemp J, Mariani TJ, Panitch H, Ren C, Shaw P, Taussig LM, Hamvas A; Prematurity and Respiratory Outcomes Program Investigators. Prematurity and respiratory outcomes program (PROP): study protocol of a prospective multicenter study of respiratory outcomes of preterm infants in the United States. BMC Pediatr. 2015 Apr 10;15:37. doi: 10.1186/s12887-015-0346-3.
PubMed 25886363Scheible KM, Emo J, Yang H, Holden-Wiltse J, Straw A, Huyck H, Misra S, Topham DJ, Ryan RM, Reynolds AM, Mariani TJ, Pryhuber GS. Developmentally determined reduction in CD31 during gestation is associated with CD8+ T cell effector differentiation in preterm infants. Clin Immunol. 2015 Dec;161(2):65-74. doi: 10.1016/j.clim.2015.07.003. Epub 2015 Jul 29.
PubMed 26232733Misra R, Shah S, Fowell D, Wang H, Scheible K, Misra S, Huyck H, Wyman C, Ryan RM, Reynolds AM, Mariani T, Katzman PJ, Pryhuber GS. Preterm cord blood CD4(+) T cells exhibit increased IL-6 production in chorioamnionitis and decreased CD4(+) T cells in bronchopulmonary dysplasia. Hum Immunol. 2015 May;76(5):329-338. doi: 10.1016/j.humimm.2015.03.007. Epub 2015 Mar 20.
PubMed 25797206Grier A, Qiu X, Bandyopadhyay S, Holden-Wiltse J, Kessler HA, Gill AL, Hamilton B, Huyck H, Misra S, Mariani TJ, Ryan RM, Scholer L, Scheible KM, Lee YH, Caserta MT, Pryhuber GS, Gill SR. Impact of prematurity and nutrition on the developing gut microbiome and preterm infant growth. Microbiome. 2017 Dec 11;5(1):158. doi: 10.1186/s40168-017-0377-0.
PubMed 29228972Hoover J, Wambach J, Vachharajani A, Warner B, Carroll JL, Kemp JS. Postmenstrual age at discharge in premature infants with and without ventilatory pattern instability. J Perinatol. 2020 Jan;40(1):157-162. doi: 10.1038/s41372-019-0530-7. Epub 2019 Oct 14.
PubMed 31611617
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prematurity and Respiratory Outcome Program: Single Center Study of Functional and Lymphocytic Markers of Respiratory Morbidity in Hyperoxic Preemies
- ClinicalTrials.gov ID
- NCT01607216
- Acronym / sponsor ID
- 37933
- Keywords
- Prematurity, Respiratory Illness, Lung Function, Lung Disease
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 277 participants (actual)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), University at Buffalo
- Study start
- Aug 2011
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 30 May 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- Up to 7 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- 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.
Key inclusion criteria (3 listed)
- 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
- 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
- Infants who are less than or equal to 7 days old
Key exclusion criteria (6 listed)
- The infant is not considered to be viable (therapies limited due to futility decision made by clinical care team)
- 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 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
4 secondary outcomes
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
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
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
Gene expression analysis of CD8 cells collected by FACS from preterm infants nearing discharge
Time frame: At 40 +/- 5 weeks corrected gestational age
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2020.
- Background: PubMed 25811285Maitre NL, Ballard RA, Ellenberg JH, Davis SD, Greenberg JM, Hamvas A, Pryhuber GS; Prematurity and Respiratory Outcomes Program. Respiratory consequences of prematurity: evolution of a diagnosis and development of a comprehensive approach. J Perinatol. 2015 May;35(5):313-321. doi: 10.1038/jp.2015.19. Epub 2015 Mar 26.
- Background: PubMed 25886363Pryhuber GS, Maitre NL, Ballard RA, Cifelli D, Davis SD, Ellenberg JH, Greenberg JM, Kemp J, Mariani TJ, Panitch H, Ren C, Shaw P, Taussig LM, Hamvas A; Prematurity and Respiratory Outcomes Program Investigators. Prematurity and respiratory outcomes program (PROP): study protocol of a prospective multicenter study of respiratory outcomes of preterm infants in the United States. BMC Pediatr. 2015 Apr 10;15:37. doi: 10.1186/s12887-015-0346-3.
- Background: PubMed 26232733Scheible KM, Emo J, Yang H, Holden-Wiltse J, Straw A, Huyck H, Misra S, Topham DJ, Ryan RM, Reynolds AM, Mariani TJ, Pryhuber GS. Developmentally determined reduction in CD31 during gestation is associated with CD8+ T cell effector differentiation in preterm infants. Clin Immunol. 2015 Dec;161(2):65-74. doi: 10.1016/j.clim.2015.07.003. Epub 2015 Jul 29.
- Results publication: PubMed 25797206Misra R, Shah S, Fowell D, Wang H, Scheible K, Misra S, Huyck H, Wyman C, Ryan RM, Reynolds AM, Mariani T, Katzman PJ, Pryhuber GS. Preterm cord blood CD4(+) T cells exhibit increased IL-6 production in chorioamnionitis and decreased CD4(+) T cells in bronchopulmonary dysplasia. Hum Immunol. 2015 May;76(5):329-338. doi: 10.1016/j.humimm.2015.03.007. Epub 2015 Mar 20.
- Results publication: PubMed 29228972Grier A, Qiu X, Bandyopadhyay S, Holden-Wiltse J, Kessler HA, Gill AL, Hamilton B, Huyck H, Misra S, Mariani TJ, Ryan RM, Scholer L, Scheible KM, Lee YH, Caserta MT, Pryhuber GS, Gill SR. Impact of prematurity and nutrition on the developing gut microbiome and preterm infant growth. Microbiome. 2017 Dec 11;5(1):158. doi: 10.1186/s40168-017-0377-0.
- Derived from this study: PubMed 31611617Hoover J, Wambach J, Vachharajani A, Warner B, Carroll JL, Kemp JS. Postmenstrual age at discharge in premature infants with and without ventilatory pattern instability. J Perinatol. 2020 Jan;40(1):157-162. doi: 10.1038/s41372-019-0530-7. Epub 2019 Oct 14.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gloria Pryhuber, MD principal investigator
University of Rochester
Rita Ryan, MD principal investigator
University at Buffalo
Thomas Mariani, PhD principal investigator
University of Rochester
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Prematurity and Symptomatic Respiratory Disease, run by University of Rochester at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Symptomatic Respiratory Disease (SRD) (time frame: Assessed every three months until 1 year corrected gestational age). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01607216, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2020.