Early-life MRI Biomarkers of Longer-term Respiratory Morbidity in Infants Born Extremely Preterm (EMBLEM)

NCT06065215 | Recruiting

• 1 other identifier: 486713
• Study Type: observational
• Target: 319
• Locations: 1 country
• Sites: 4

Brief Summary

Bronchopulmonary dysplasia (BPD) is a common, major complication of premature birth, associated with developmental and health consequences that continue into adulthood. Prediction of who will have these problems is challenging using traditional definitions of disease. It is believed that underdevelopment and injury occur in both lung tissue and the blood vessels in the lungs, with a sophisticated interplay between them that contributes to lung disease seen in prematurity. New magnetic resonance imaging (MRI) techniques can delineate tissue structure with unprecedented granularity, assessing lung tissue, blood vessels, and their interplay. The ability to identify, at an early stage, those infants destined for chronic lung disease with greater certainty will be useful in counseling families and critical for the effective introduction of promising new BPD therapies. 319 infants born less than 29 weeks gestation will be recruited from 4 centres, including 5 babies who received stem cell therapy in a clinical trial. Babies will be evaluated at 36 weeks post-conception with lung MRI, oscillometry (lung function), echocardiogram (heart ultrasound), and oscillometry. Lung health will be assessed every 3 months by phone questionnaire and chart review. At 18-21 months post-conception, babies will undergo neurodevelopmental assessment and lung function testing. The investigators will look at how well baseline MRI markers predict subsequent lung health and development, independently and combined with echocardiogram, lung ultrasound, and traditional markers of BPD. The investigators anticipate that these new MRI markers will measure lung health safely and longitudinally in babies born extremely preterm. By identifying predictors of longer-term lung disease, clinicians will be able to allocate resources to babies at the highest risk of severe disease. Further, The investigators envision that MRI will help identify babies who would benefit most from interventions like stem cell therapy and be useful for evaluation of future treatments.

Conditions

Lung Function; BPD - Bronchopulmonary Dysplasia

Outcome Measures

Primary Outcomes (1)

• Severe Post-prematurity Respiratory Disease (PRD)

  PRD will be defined based on the consensus definition of the Prematurity and Respiratory Outcomes Program. This composite outcome characterizes clinically relevant persistent respiratory morbidity in early life. It will be evaluated every 3 months from 36 weeks PMA to 18 months corrected age through parent questionnaire and chart review. Severe PRD is defined as a positive response to any of the following: ≥2 respiratory-related hospitalizations, home oxygen at 3 months corrected age or any home respiratory support, systemic corticosteroid or pulmonary vasodilators after discharge home, chronic respiratory symptoms (cough without cold or wheeze at least once per week) despite concurrent inhaled corticosteroids in ≥ 2 questionnaires, or death secondary to a cardiopulmonary cause. PRD has been used as a clinical outcome in cohort studies and an American Thoracic Society guideline on optimal neonatal care pathways and predictive perinatal characteristics.

  The evaluation will be conducted at regular intervals of every 3 months, commencing at 36 weeks PMA and continuing until the child reaches 18 months corrected age

Secondary Outcomes (1)

• Neurodevelopmental Impairment (NDI)

  Neurodevelopmental impairment will be determined at the 18-21 months corrected age visit

Interventions

Magnetic Resonance Imaging (MRI) DIAGNOSTIC_TEST

Magnetic Resonance Imaging (MRI) is a non-invasive medical imaging technique that uses powerful magnets and radio waves to generate detailed images of the body's internal structures. The MRI intervention includes using a specialized MRI machine and lung imaging protocol.

Echocardiogram DIAGNOSTIC_TEST

An echocardiogram, often called an "echo," is a non-invasive medical test that uses high-frequency sound waves (ultrasound) to create real-time images of the heart's structure and function. It provides valuable information about the heart's size, shape, and function.

Lung ultrasound DIAGNOSTIC_TEST

Lung ultrasound is a non-invasive imaging technique that employs high-frequency sound waves (ultrasound) to visualize the structures and conditions of the lungs. It is particularly valuable for diagnosing and monitoring lung-related conditions, such as pneumonia, pleural effusions, and pulmonary edema. The lung ultrasound intervention involves using an ultrasound machine equipped with a specialized probe gently placed on the chest to capture detailed images of the lungs and adjacent structures.

Eligibility Criteria

• Age: 35 Weeks - 21 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Babies will be recruited from four Canadian tertiary care pediatric centers: Children's Hospital of Eastern Ontario (CHEO), Ottawa, ON; Mount Sinai Hospital, Toronto, ON; Centre Hospitalier Universitaire Sainte-Justine, Montreal QC; and Montreal Children's Hospital, Montreal QC. MRI will occur at each site except Mount Sinai, whose babies will undergo MRI at The Hospital for Sick Children, Toronto, ON.

You may qualify if:

• Infants born at \<29 weeks gestation;
• currently \<36 weeks PMA.

You may not qualify if:

• Known interstitial lung disease, congenital lung anomaly, ciliary dysfunction, immunodeficiency, cystic fibrosis, neuromuscular disease, or structural heart disease (other than atrial septal defect/hemodynamically insignificant ventricular septal defect/patent ductus arteriosus);
• genetic syndrome or congenital anomaly;
• contraindications for MRI or transport;
• invasive or non-invasive ventilation that cannot be safely removed for MRI;
• current respiratory infection;
• family cannot speak English/French;
• transferred to another hospital prior to baseline study visit
• not receiving follow-up at one of the study centres.

Sponsors & Collaborators

• Children's Hospital of Eastern Ontario: lead
• The Hospital for Sick Children: collaborator
• MOUNT SINAI HOSPITAL: collaborator
• Hannover Medical School: collaborator
• St. Justine's Hospital: collaborator
• Montreal Children's Hospital of the MUHC: collaborator

Study Sites (4)

The Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

RECRUITING

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

RECRUITING

CHU-Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

ACTIVE NOT RECRUITING

Montreal Children's Hospital

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

MeSH Terms

Conditions

Bronchopulmonary Dysplasia

Interventions

Magnetic Resonance Imaging; Echocardiography

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)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Cardiac Imaging Techniques; Ultrasonography; Heart Function Tests; Diagnostic Techniques, Cardiovascular

Study Officials

• Sherri Katz

  Children's Hospital of Eastern Ontario

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sherri Katz

CONTACT

(613) 737-7600; skatz@cheo.on.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Division Head, Senior Scientist, Pediatric Respirologist

Study Record Dates

• First Submitted: September 27, 2023
• First Posted: October 3, 2023
• Study Start: March 30, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: February 24, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)