Phenotypic and Genetic Assessment of Tracheal and Esophageal Birth Defects in Patients

NCT03455881 | Unknown

• 2 other identifiers: CIN_PhenoandGeneticTED_0011P01HD093363-01
• Study Type: observational
• Target: 360
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators propose a preliminary study performing exome sequencing on samples from patients and their biologically related family members with tracheal and esophageal birth defects (TED). The purpose of this study is to determine if patients diagnosed with TED and similar disorders carry distinct mutations that lead to predisposition. The investigators will use advanced, non-invasive magnetic resonance imaging (MRI) techniques to assess tracheal esophageal, lung, and cardiac morphology and function in Neonatal Intensive Care Unit (NICU) patients. MRI techniques is done exclusively if patient is clinically treated at primary study location and if patient has not yet had their initial esophageal repair.

Conditions

Tracheoesophageal Fistula; Esophageal Atresia; Laryngeal Cleft; Tracheal Stenosis; Bronchial Stenosis; Esophageal Bronchus; Congenital High Airway Obstruction Syndrome

Keywords

TEF; EA; Tracheal Esophageal birth Defect (TED)

Outcome Measures

Primary Outcomes (2)

• Genomic Sequencing

  Identify novel genes and mutations in patients with TEDs using trio genomic sequencing of TED patients and their parents.

  1 day

• Anatomic phenotypes using MRI

  Investigate the esophageal, tracheal, mediastinal and pulmonary anatomy in patients with TEDs.

  1 day

Secondary Outcomes (1)

• Change in the anatomic phenotype using MRI

  Change in MRI from pre-repair to discharge

Study Arms (4)

NICU TED Genetic Cohort

This study involves one inpatient biofluid collection encounter from the subject, one biofluid collection encounter from each biological parent, and an optional biofluid collection encounter from other biological family members.

NICU TED MRI Cohort

This study involves up to three inpatient NICU MRI encounters. The first MRI may be done before surgical repair if the clinical team feels the infant is clinically stable. The second MRI may be completed post-surgical repair of TED. An additional 3rd MRI may be done prior to the time of discharge from the NICU. The pre repair, post-surgical, and pre discharge MRIs will provide valuable data for the understanding of tracheal esophageal malformation disorders and may provide clinical guidance for the participant's care.

TED Genetic Cohort

This study involves one biofluid collection encounter from the subject, one biofluid collection encounter from each biological parent, and an optional biofluid collection encounter from other biological family members.

NICU Control MRI Cohort

This study involves two inpatient NICU MRI encounters. The first MRI will occur within the first month of life, and the second MRI will occur prior to discharge.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Approximately 100 NICU TED patient/parent trios for the NICU TED Genetic cohort. Approximately 100 NICU TED patients for the NICU TED MRI cohort. These patients will also be in the NICU TED cohort. Approximately 155 TED patient/parent trios from the Esophageal Center for the Esophageal Center Genetic cohort. Approximately 5 NICU infants with normal tracheal and esophageal anatomy for the NICU Control MRI cohort.

You may qualify if:

• Patient that has been diagnosed by clinical team with a congenital TED OR family member to the TED diagnosed patient.
• Willingness to donate biological specimens.
• Ability to consent/assent as appropriate.

You may not qualify if:

• Unable to determine or unavailable parent trio.
• Unable to provide DNA sample.
• Inability to provide consent.
• NICU TED Genetic Cohort:
• Infant born between 24 and 42 weeks PMA.
• TED diagnosed by clinical team.
• Inpatient in the Neonatal Intensive Care Unit (NICU) OR family member to the inpatient in the NICU.
• Willingness to donate biological specimens.
• Ability to consent/assent as appropriate.
• Unable to determine or unavailable parent trio.
• Unable to provide DNA sample.
• Inability to provide consent.
• NICU TED MRI Cohort:
• Infant born between 24 and 42 weeks PMA.
• TED diagnosed by clinical team.

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Columbia University: collaborator

Study Sites (1)

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

RECRUITING

Related Publications (19)

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• Mahalik SK, Sodhi KS, Narasimhan KL, Rao KL. Role of preoperative 3D CT reconstruction for evaluation of patients with esophageal atresia and tracheoesophageal fistula. Pediatr Surg Int. 2012 Oct;28(10):961-6. doi: 10.1007/s00383-012-3111-9. Epub 2012 Jun 22.

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Biospecimen

Retention: SAMPLES WITH DNA

Biofluids, such as, blood and/or salvia and surgical tissue samples

MeSH Terms

Conditions

Tracheoesophageal Fistula; Esophageal Atresia; Laryngeal cleft; Tracheal Stenosis

Condition Hierarchy (Ancestors)

Esophageal Fistula; Digestive System Fistula; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Respiratory Tract Fistula; Respiratory Tract Diseases; Tracheal Diseases; Fistula; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Digestive System Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Paul Kingma, MD, PhD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paul Kingma, MD, PhD

CONTACT

(513)636-2995; paul.kingma@cchmc.org

Study Design

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

Study Record Dates

• First Submitted: February 12, 2018
• First Posted: March 7, 2018
• Study Start: March 28, 2018
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2026
• Last Updated: March 8, 2023

Record last verified: 2023-03

Locations

US (1)