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

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ClinicalTrials.gov Identifier: NCT01661491
Recruitment Status : Recruiting
First Posted : August 9, 2012
Last Update Posted : July 4, 2019
Sponsor:
Information provided by (Responsible Party):
Yale University

Tracking Information
First Submitted Date August 6, 2012
First Posted Date August 9, 2012
Last Update Posted Date July 4, 2019
Study Start Date August 2012
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: September 10, 2012)
Change from Baseline in the Average Unifrac Value in Fecal Microbiome & Metagenome Composition at 4 years [ Time Frame: 4 years ]
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
Original Primary Outcome Measures
 (submitted: August 6, 2012)
  • Fecal microbiome & metagenome composition [ Time Frame: Every 3 months for 4 years ]
    High throughput sequencing will be used to identify microbial taxa and microbial genes present in feces
  • Fecal inflammatory markers [ Time Frame: Every 3 months x 4 years ]
    Inflammatory markers (including fecal calprotectin, short chain fatty acids, rectal nitric oxide)
Change History Complete list of historical versions of study NCT01661491 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: July 2, 2019)
  • Change from Baseline in the Amounts of Calprotectin at 4 years [ Time Frame: 4 years ]
    Fecal calprotectin will be measured by elisa
  • Change from Baseline in the Amounts of Short Chain Fatty Acids at 4 years [ Time Frame: 4 years ]
    Fecal short chain fatty acids will be measured by gas chromatography
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Microbiome Acquisition and Progression of Inflammation and Airway Disease in Infants and Children With Cystic Fibrosis
Official Title Microbiome Acquisition and Progression of Inflammation and Airway Disease in Infants and Children With Cystic Fibrosis
Brief Summary 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.
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.

Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
Fecal samples
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.
Condition Cystic Fibrosis
Intervention Not Provided
Study Groups/Cohorts
  • Cystic Fibrosis
    Infants and toddlers with Cystic Fibrosis
  • Non-cystic fibrosis controls
    Infants and toddlers without Cystic Fibrosis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: August 6, 2012)
60
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 2020
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility 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
Sex/Gender
Sexes Eligible for Study: All
Ages 3 Months to 4 Years   (Child)
Accepts Healthy Volunteers Yes
Contacts
Contact: Marie Egan, MD (203) 785-2480 marie.egan@yale.edu
Contact: Barbara Kazmierczak, MD, PhD (203) 785-4140 barbara.kazmierczak@yale.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT01661491
Other Study ID Numbers 1206010476
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Yale University
Study Sponsor Yale University
Collaborators Not Provided
Investigators
Principal Investigator: Barbara I Kazmierczak, MD PhD Yale University
Principal Investigator: Marie Egan, MD Yale University
PRS Account Yale University
Verification Date July 2019