Multidimensional Phenotype Classification in Grade 3 Bronchopulmonary Dysplasia

NCT06475976 | Recruiting DMC

• 2 other identifiers: 23-021005R01HL168066
• Study Type: observational
• Target: 130
• Locations: 1 country
• Sites: 1

Brief Summary

Bronchopulmonary Dysplasia (BPD), or chronic lung disease of prematurity, is the most consequential complication of preterm birth and is strong predictor of childhood pulmonary and neurodevelopmental disability, particularly in infants diagnosed with grade 3 BPD (ventilator dependence at 36 weeks' postmenstrual age), the most severe disease form. This study aims to (1) generate the first empirically defined phenotype classification system for grade 3 BPD developed using a rich array of objective and quantitative cardiopulmonary diagnostic, clinical, and biological data; and (2) define the association between phenotype subgroups and neurodevelopmental and respiratory outcomes through 2 years' corrected age.

Conditions

Bronchopulmonary Dysplasia

Keywords

Bronchopulmonary Dysplasia; BPD; Multidimensional Phenotype

Outcome Measures

Primary Outcomes (1)

• Empirically defined phenotype subgroup

  The number and characteristics of phenotype subgroups will be empirically defined using cluster analyses applied to the collected cardiopulmonary diagnostic and clinical data. All recorded diagnostic and clinical information will be considered for inclusion in these analyses. Final study reports will indicate which diagnostic and clinical data were most associated with cluster classification. The strength of association between assigned cluster and neurodevelopmental and respiratory outcomes assessed through 26 months' corrected age will be defined.

  Up to 26 months' corrected age

Secondary Outcomes (6)

• Moderate to severe neurodevelopmental impairment (NDI)

  Up to 26 months' corrected age

• Total problem behavior score

  Up to 26 months' corrected age

• Health related quality of life

  Up to 26 months' corrected age

• Abnormal respiratory signs/symptoms

  Up to 26 months' corrected age

• Moderate to severe respiratory compromise

  Up to 26 months' corrected age

Study Arms (1)

Diagnostic cohort

Study participants will undergo the following diagnostic tests:

Diagnostic Test: Chest computed tomography (CT) with angiography; Diagnostic Test: Bronchoscopy with bronchoalveolar lavage; Diagnostic Test: Echocardiography; Diagnostic Test: 24 hour esophageal pH ("potential of hydrogen") - multichannel intraluminal impedance (MII) monitoring (reflux testing)

Interventions

Chest computed tomography (CT) with angiography DIAGNOSTIC_TEST

A CT scan uses a doughnut-shaped machine to take x-rays in a circle around the body. CT scans help doctors learn about the structure of the lungs, heart, and blood vessels in the chest. A CT scan provides more information than regular x-rays. CT w/angiography - injection of intravenous contrast during the CT to image the blood vessels within the chest.

Diagnostic cohort

Bronchoscopy with bronchoalveolar lavage DIAGNOSTIC_TEST

During a bronchoscopy, a lung doctor inserts a small flexible camera into the breathing tube and main branches of the airways within the lungs. During the test, a small amount of sterile fluid is placed into the lung and then retrieved (lavage). This fluid is tested for evidence of infection.

Diagnostic cohort

Echocardiography DIAGNOSTIC_TEST

An echo uses sound waves to create computer pictures of the heart.

Diagnostic cohort

24 hour esophageal pH ("potential of hydrogen") - multichannel intraluminal impedance (MII) monitoring (reflux testing) DIAGNOSTIC_TEST

24 hour pH/MII testing is used to measure gastroesophageal reflux. A small feeding tube like catheter is passed through the nose or mouth into the esophagus. The catheter is used to measure the frequency and acidity of reflux episodes during a 24 hour monitoring period.

Diagnostic cohort

Eligibility Criteria

• Age: 1 Month - 1 Year
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

This study will enroll male and female infants born very premature and who are receiving prolonged invasive ventilation at the time of study enrollment between 36 and 65 weeks postmenstrual age for high grade (2 or 3) bronchopulmonary dysplasia. A parent or guardian caregiver will be enrolled as a dyad with the enrolled infant to facilitate collection of parental stress index data through 2 year follow-up.

You may qualify if:

• Male or female infant born with gestational age \<32 weeks
• Postmenstrual age between 36-65 weeks at enrollment
• Receiving invasive ventilation at enrollment
• Grade 3 BPD or grade 2 BPD with need for chronic invasive ventilation at enrollment
• Parental informed consent (provides the consent to participate)

You may not qualify if:

• Contraindication to 1 or more of the study diagnostic procedures
• Family unable/unlikely to commit to 2-year follow-up
• Unlikely to survive the 6-8-week diagnostic period
• Parental consent not provided (decline consenting for study)
• Aneuploidy or other severe congenital abnormality not-representative in BPD
• At the time of consent, a parent or guardian caregiver will be invited to participate as an enrolled dyad using the following eligibility criteria:
• Parent or legal guardian of an enrolled infant subject
• Informed consent
• Unable/unlikely to complete study procedures

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Tracheal aspirate fluid Blood Urine Stool Bronchoalveolar Lavage (BAL)

MeSH Terms

Conditions

Bronchopulmonary Dysplasia

Interventions

Bronchoscopy; Echocardiography; Hydrogen-Ion Concentration

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Pulmonary Surgical Procedures; Thoracic Surgical Procedures; Cardiac Imaging Techniques; Diagnostic Imaging; Ultrasonography; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Chemical Phenomena

Study Officials

• Erik Jensen, MD, MSCE

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

• Krithika Lingappan, MD, PhD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Erik Jensen, MD, MSCE

CONTACT

267-648-2720; jensene@chop.edu

Krithika Lingappan, MD, PhD

CONTACT

8324058684; lingappank@chop.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2024
• First Posted: June 26, 2024
• Study Start: December 5, 2023
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): July 31, 2029
• Last Updated: July 20, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data will be available following completion of all study procedures, follow-up assessments, and primary data analyses.
• Access Criteria: Researchers with a bonafide interest and suitable plan of use will be granted access to the study data.

Locations

US (1)