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Lung Obstruction in Adulthood of Prematurely Born (LUNAPRE) (LUNAPRE)

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ClinicalTrials.gov Identifier: NCT02923648
Recruitment Status : Recruiting
First Posted : October 4, 2016
Last Update Posted : October 6, 2016
Sponsor:
Collaborators:
Swedish Heart Lung Foundation
The Swedish Research Council
Stockholm County Council, Sweden
Stockholm South General Hospital
University of California, San Francisco
Kyoto University
Göteborg University
University of Oulu
Information provided by (Responsible Party):
Asa Wheelock, Karolinska Institutet

Brief Summary:
Obstructive lung disease is an increasing global health problem of pandemic proportions, with COPD alone affecting >10% of the population. Smoking is the main and most well studies risk factor for developing COPD. However, chronic airway obstruction also in never-smoking populations has recently been recognized as an increasing health problem. Prematurely born children, particularly survivors of bronchopulmonary dysplasia (BPD), defined as the need for oxygen therapy up to the 28th day of life for children born prior to gestational week 32, have an increased incidence of both airway obstruction and hyper-reactivity, both representing major risk factors for developing COPD, or asthma, later in life. The purpose of this study is to perform in-depth clinical and molecular characterizations of of the lungs of survivors of BPD as they enter adulthood, and compare these profiles to relevant control groups (individuals with mild asthma, healthy prematurely born, and healthy individuals born at full term). Specifically, alterations at the epigenetic, mRNA, microRNA, protein and metabolite level as well as associated molecular pathways critical in the pathological mechanisms of obstructive lung disease related to premature birth and BPD will be identified.

Condition or disease
Premature Birth- and BPD-related Obstructive Lung Disease

Detailed Description:
Chronic Obstructive Pulmonary Disease (COPD) is an umbrella diagnosis defined by obstructive lung function impairments, and is likely to be caused by a multitude of etiologies including environmental exposures, genetic predispositions and developmental factors. Due to the heterogeneity of the disease, molecular and mechanistic sub-phenotyping of COPD represents an essential step to facilitate the development of relevant diagnostic and treatment options for this constantly growing patient group. Obstructive lung disease is an increasing global health problem of pandemic proportions, with COPD alone affecting >10% of the population, and predicted by WHO to become the 5th leading cause of morbidity and disability worldwide by year 2020. Smoking is the main and most well studies risk factor for developing COPD. However, chronic airway obstruction also in never-smoking populations has recently been recognized as an increasing health problem: An estimated 10% of patient diagnosed with COPD have never smoked, representing 1% of the general public. Low birth weight and premature birth represent important risk factors for developing pulmonary obstruction in adulthood. Particularly prematurely born children with bronchopulmonary dysplasia (BPD), defined as the need for oxygen therapy up to the 28th day of life for children born prior to gestational week 32, have an increased incidence of both airway obstruction and hyper-reactivity, both representing major risk factors for developing COPD, or asthma, later in life. The purpose of the LUNAPRE study is to perform in-depth clinical and molecular characterizations of of the lungs of survivors of BPD as they enter adulthood, and compare these profiles to relevant control groups. The study encompasses profiling of epigenetic alterations, mRNA, miRNA, proteomes, metabolomes and lipid mediators from multiple lung compartments (airway epithelium, alveolar macrophages, exosomes, and bronchoalveolar exudates) using a range of 'omics platforms, in combination with extensive clinical phenotyping of very prematurely born subjects with- and without BPD in the neonatal period as they enter adulthood, as well as healthy subjects with mild asthma born at term. The primary objective of the study is to identify molecular alterations that persist into adulthood that are related to early onset obstructive lung disease, specifically by correlating clinical phenotypes with multi-molecular 'omics profiling from several lung compartments of the study groups. Secondary goals involve identification of subsets of prognostic/diagnostic biomarkers for classification of the defined subgroups, as well as relevant pharmaceutical targets.

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Study Type : Observational
Estimated Enrollment : 102 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Lung Obstruction in Adulthood of Prematurely Born (LUNAPRE)
Study Start Date : March 2013
Estimated Primary Completion Date : December 2016
Estimated Study Completion Date : December 2021

Group/Cohort
Very prematurely born with BPD
Very prematurely born (gestational age [GA]< 32 weeks) with bronchopulmonary dysplasia (BPD) as defined by Jobe and Bancalari 2001, age 18-22.
Very prematurely born without BPD
Very prematurely born (GA< 32 weeks) without BPD in the neonatal period, age 18-22
Asthma full-term control group
Subjects with mild atopic asthma, born at term (GA> 37 weeks), age 18-22
Healthy full-term control group
Healthy participants, born at term (GA>37 weeks), age 18-22



Primary Outcome Measures :
  1. Forced expiratory volume in 1 second (FEV1) including reversibilityForced expiratory volume in 1 second (FEV1) including reversibilityForced expiratory volume in 1 second (FEV1) including reversibility [ Time Frame: Measured at baseline ]
  2. Forced Vital Capacity (FVC) including reversibility [ Time Frame: Measured at baseline ]
  3. Impulse oscillometry [ Time Frame: Measured at baseline ]
  4. Airway hyper-reactivity (methacholine test) [ Time Frame: Measured at baseline ]
  5. Emphysema and airway wall thickness, as shown on low radiation chest CT scan [ Time Frame: Measured at baseline ]

Secondary Outcome Measures :
  1. COPD status (according to GOLD initiative standards as well as LLN) [ Time Frame: Determined at baseline ]
  2. Molecular alterations due to BPD and/or premature birth persisting into adulthood [ Time Frame: Determined at baseline ]
  3. Molecular gender differences [ Time Frame: Determined at baseline ]

Biospecimen Retention:   Samples With DNA
Bronchoalveolar lavage (BAL) cells, BAL fluid, bronchial biopsies, airway epithelial brushings, serum, plasma, blood cells, and urine are collected and stored.


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 22 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Participants from the two prematurely born groups are recruited from cohort sfollowed since birth at Sach's Children's Hospital, Stockholm. Participants in the full term born groups are recruited from the general population through advertisements.
Criteria

Inclusion Criteria:

  • Spirometry of postbronchodilator forced expiratory volume in 1 second (FEV1) >50% of predicted level for premature groups

Exclusion Criteria:

  • Smoking
  • Other lung diseases
  • Received antibiotics in the 3 months prior to study entry
  • Treatment with oral or inhaled glucocorticoids within past 3 months prior to study entry

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): NCT02923648


Contacts
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Contact: Magnus Skold, MD, PhD magnus.skold@ki.se
Contact: Asa M Wheelock, PhD asa.wheelock@ki.se

Locations
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Sweden
Karolinska Institutet/Karolinska University Hospital Solna Recruiting
Stockholm, Sverige, Sweden, 17176
Contact: Magnus Skold, MD, PhD       magnus.skold@ki.se   
Contact: Asa M Wheelock, PhD       asa.wheelock@ki.se   
Principal Investigator: C. Magnus Skold, MD, PhD         
Principal Investigator: Asa M Wheelock, PhD         
Stockholm Southern General Hospital Recruiting
Stockholm, Sweden
Contact: Eva Berggren-Broström, MD, PhD         
Sponsors and Collaborators
Karolinska Institutet
Swedish Heart Lung Foundation
The Swedish Research Council
Stockholm County Council, Sweden
Stockholm South General Hospital
University of California, San Francisco
Kyoto University
Göteborg University
University of Oulu
Investigators
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Principal Investigator: Magnus Skold, MD, PhD Karolinska Institute, Karolinska University Hospital
Principal Investigator: Asa M Wheelock, PhD Karolinska Institutet
Principal Investigator: Erik Melén, MD, PhD Karolinska Institute, Stockholm Southern General Hospital
Principal Investigator: Eva Berggren-Brostrom, MD, PhD Stockholm Southern General Hospital
Principal Investigator: Anders Lindén, MD, PhD Karolinska Institute, Karolinska University Hospital
Principal Investigator: Sven Nyrén, MD, PhD Karolinska Institute, Karolinska University Hospital

Publications:
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Responsible Party: Asa Wheelock, Associate professor, Karolinska Institutet
ClinicalTrials.gov Identifier: NCT02923648     History of Changes
Other Study ID Numbers: 2012/1872-31/4
First Posted: October 4, 2016    Key Record Dates
Last Update Posted: October 6, 2016
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
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Lung Diseases
Premature Birth
Lung Diseases, Obstructive
Respiratory Tract Diseases
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications