Microbiome Acquisition and Progression of Inflammation and Airway Disease in Infants and Children With Cystic Fibrosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Yale University
Sponsor:
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT01661491
First received: August 6, 2012
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

Cystic Fibrosis (CF) is a fatal, recessive genetic disorder characterized by progressive inflammation and lung damage. It is unclear whether current treatment strategies, which focus on detection and eradication of pathogenic microorganisms in the lung, are the best way to prevent the initiation of early inflammation and lung damage. This study asks how early acquisition of microbial flora occurs in infants with CF and healthy baby controls, and whether this process initiates or influences early inflammation and clinical disease progression in CF.


Condition
Cystic Fibrosis

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Microbiome Acquisition and Progression of Inflammation and Airway Disease in Infants and Children With Cystic Fibrosis

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Change from Baseline in the Average Unifrac Value in Fecal Microbiome & Metagenome Composition at 4 years [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    High throughput sequencing will be used to identify microbial taxa and microbial genes present in feces, and to determine how these change over a period of 4 years


Secondary Outcome Measures:
  • Change from Baseline in the Amounts of Calprotectin at 4 years [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Change from Baseline in the Amounts of Short Chain Fatty Acids at 4 years [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Change from Baseline in the Amounts of Nitric Oxide at 4 years [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

Fecal samples


Estimated Enrollment: 60
Study Start Date: August 2012
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)
Groups/Cohorts
Cystic Fibrosis
Non-cystic fibrosis controls

Detailed Description:

Cystic Fibrosis is the most common lethal genetic disorder in Caucasian populations. Mutations of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) affect its ability to act as a chloride channel. The recent development of a transgenic pig model of CF has demonstrated that newborn CF lungs, free of bacteria and inflammation at birth, become colonized with a mixed microbial flora that likely initiates early inflammatory changes which precede clinically apparent deterioration in lung function.

Because chronic infection and inflammation play central roles in CF disease progression and exacerbations, many clinicians and researchers have focused on identifying pathogens associated with CF infection and inflammation. Recent studies outside the area of CF, however, have clearly demonstrated that "non-pathogens", such as the commensal flora carried by all humans at multiple mucosal sites, engage the host's innate and adaptive immune systems constantly. This interaction between "microbiome" and host genome is responsible for appropriate development and function of protective inflammatory and immune responses.

We hypothesize that acquisition of a commensal flora by newborns with CF may play a critical role in initiating pathogenic inflammatory responses that subsequently lead to lung damage. The acquired commensal flora may initially be identical to that of a non-CF infant, but may be altered by the direct or indirect effects of CFTR mutation on the mucosal environment. Such an altered flora is likely to encode different metabolic and regulatory functions, and may directly influence host inflammatory responses. If so, a novel therapeutic opportunity may exist to modulate this commensal flora, or to manipulate its immunomodulatory functions in a way that interrupts the insidious cycle of inflammation and damage that characterizes CF.

We propose to test our hypothesis in three specific aims: (1) Describe the acquisition and evolution of gut and respiratory tract microbiomes in CF infants and non-CF controls; (2) Determine the relationship between the microbiota and markers of inflammation in these two cohorts; and (3) Determine whether early declines in lung function are associated with inflammatory biomarkers or microbiome composition/function. This study is novel in its focus on a rarely studied population, at a time when interventions might significantly impact progression of this lethal disease and preserve pulmonary function. Its innovation lies in applying state of the art technologies and methods to samples that can be collected simply and non-invasively, thus increasing the likelihood that the findings of this study can be translated into clinical practice.

  Eligibility

Ages Eligible for Study:   3 Months to 4 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Infants and children up to the age of 4 with Cystic Fibrosis, and age-matched controls without cystic fibrosis will be eligible for this study. Participants will be recruited from the Cystic Fibrosis clinic and Primary Care Clinic of the Yale New Haven Hospital.

Criteria

Cystic Fibrosis participants:

Inclusion Criteria:

  • laboratory diagnosis of Cystic Fibrosis

Exclusion Criteria:

  • Major organ system disease other than Cystic Fibrosis
  • History of prematurity

Non Cystic Fibrosis control participants:

Inclusion Criteria:

  • Proof of a negative newborn CF screening test

Exclusion Criteria:

  • Major organ system disease
  • History of prematurity
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01661491

Contacts
Contact: Marie Egan, MD (203) 785-2480 marie.egan@yale.edu
Contact: Barbara Kazmierczak, MD, PhD (203) 785-4140 barbara.kazmierczak@yale.edu

Locations
United States, Connecticut
Cystic Fibrosis Clinic, Yale New Haven Hospital Recruiting
New Haven, Connecticut, United States, 06520
Contact: Marie Egan, MD    203-785-2480      
Primary Care Clinic, Yale New Haven Hospital Not yet recruiting
New Haven, Connecticut, United States, 06520
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Barbara I Kazmierczak, MD PhD Yale University
Principal Investigator: Marie Egan, MD Yale University
  More Information

No publications provided

Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT01661491     History of Changes
Other Study ID Numbers: 1206010476
Study First Received: August 6, 2012
Last Updated: June 12, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Inflammation
Fibrosis
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases

ClinicalTrials.gov processed this record on October 16, 2014