Viral Pathogenesis of Early Cystic Fibrosis Lung Disease (Early CF)

The purpose of this study is to test the hypothesis that early viral infections alter the bacterial flora and inflammatory profile in the airway and accelerate progression of pulmonary disease in infants with cystic fibrosis.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis

Detailed Description

The proposed study is a unique international collaboration between three large CF research centers. This proposal will determine the impact of early respiratory viral infections on bacterial flora and inflammatory profiles in the CF airway as well as the impact of these pathogens on clinical, physiologic and structural markers of disease.The proposed study is designed to follow infants diagnosed with CF through newborn screening to determine the effect of viral infections on the lower airway microbiome, clinical symptoms, pulmonary function and structural changes during the first year of life. The proposed study will measure lower airway inflammation and infection using BAL, oral swabs, and nasal swabs; outcomes will be assessed through infant lung function testing, computerized tomography scans of the chest, and pulmonary exacerbation rate.

• Study Type: Observational
• Enrollment (Actual): 65

Contacts and Locations

Study Locations

• Australia
  • West Perth, Australia, 6872
    • Telethon Kids Institute
  • Victoria
    • Melbourne, Victoria, Australia
      • The Royal Children's Hospital
• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children at Indiana University Health
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • St. Louis Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 4 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Infants, less than 4 months of age who have been diagnosed with Cystic Fibrosis

Description

Inclusion Criteria:

1. Diagnosis of CF by newborn screening, at least one clinical feature of CF, and documented sweat chloride greater than 60 mEq/L by quantitative pilocarpine iontophoresis or compatible genotype with two identifiable mutant CFTR alleles.
2. Less than 4 months of age at Screening Visit
3. Ability to comply with study visits and study procedures as judged by site investigator.

Exclusion Criteria:

1. Intercurrent respiratory illness, defined as increase in cough, wheezing, or respiratory rate with onset 14 days before iPFT-bronchoscopy visit.
2. Measured hemoglobin oxygen saturation less than 95% during the iPFT-bronchoscopy visit.
3. History of adverse reaction to sedation.
4. Clinically significant upper airway obstruction as determined by the site investigator.
5. Severe gastroesophageal reflux, defined as persistent frequent emesis despite therapy.
6. Major organ dysfunction, not including pancreatic dysfunction.
7. Physical findings that would compromise the safety of the subject or the quality of the study data as determined by site investigator.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral infection	To determine the effect(s) of viral infections on the evolution of endobronchial bacterial infection and inflammation in CF infants.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary exacerbation rate	To identify the impact of respiratory viruses on the onset, frequency, and duration of respiratory symptoms in CF infants diagnosed through newborn screening.	12 Months
Forced Expiratory Volume	To assess development of early lung disease as defined through physiological measures of forced expiratory flows, lung volumes, and ventilation inhomogeneity in CF infants.	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bronchiectasis	To evaluate the association of early viruses on the development of early lung disease in CF infants as defined through comprehensive structural and airway modeling techniques.	12 Months

Collaborators and Investigators

• Sponsor: Indiana University School of Medicine
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Stephanie D. Davis, MD, Indiana University School of Medicine

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: September 17, 2013
• First Submitted That Met QC Criteria: October 25, 2013
• First Posted (Estimate): October 31, 2013

Study Record Updates

• Last Update Posted (Actual): April 4, 2017
• Last Update Submitted That Met QC Criteria: April 3, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Lung Diseases; Pulmonary Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: 1R01HL116211-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No