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A Two-Part Multicenter Prospective Longitudinal Study of CFTR-dependent Disease Profiling in Cystic Fibrosis (PROSPECT)

Completed
Conditions
Cystic Fibrosis
Interventions
Other: Observational
Registration Number
NCT02477319
Lead Sponsor
University of Alabama at Birmingham
Brief Summary

identify and validate biomarkers that might reflect partial restoration of CFTR function and can be used to monitor disease progression, and ii) evaluate the mechanistic effects of CFTR modulators and other relevant therapies in individuals with CF

Detailed Description

Cystic fibrosis (CF) is a genetic disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Over 1,900 mutations, categorized into five genotypic or functional classes are implicated in causing CF. Severity of disease varies widely in CF based on CFTR-dependent and independent factors. Progressive obstructive lung disease is the main determinant of morbidity and mortality in CF; therefore it is critical to identify biomarker profiles that reflect and predict this phenotypic variability, and understand their relationship to residual CFTR activity. Emerging CFTR modulator therapies that directly target defective CFTR are being evaluated in pivotal clinical trials and may become available in the next few years. It is not known how partial restoration of CFTR function might impact CF disease progression and disease-related biomarkers. Thus there is urgent need to i) identify and validate biomarkers that might reflect partial restoration of CFTR function and can be used to monitor disease progression, and ii) evaluate the mechanistic effects of CFTR modulators and other relevant therapies in individuals with CF

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
452
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Part AObservational* Cohort 1: Healthy Controls * Cohort 2: Partial CFTR function CF (class IV/V) * Cohort 3: Absent CFTR function CF (Class I/II)
Part BObservationalCF patients who are homozygous for the F508del
Primary Outcome Measures
NameTimeMethod
Sweat Chloride by Cohort (Part A Only)For cohort 1, sweat chloride at Day 0 is time frame. For cohorts 2-3, sweat chloride averaged across all 3 visits at days 0, 14 and 90 is time frame.

This is the primary endpoint for Part A per the PROSPECT protocol. Mean sweat chloride was not reported for Part B, as it is not a relevant statistic.

For cohort 1, sweat chloride is from day 0 only. For cohorts 2-3, sweat chloride was averaged from days 0, 14, 90 via a random intercept longitudinal model.

6 Month Change in FEV1 Percent Predicted (Part B Only)Baseline and 6 months

This is the primary endpoint for Part B per the PROSPECT protocol. Change in FEV1 Percent Predicted is only relevant for Part B as it captures changes in lung function post-initiation of Ivacaftor/Lumacaftor.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (38)

Children's Hospital of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

Hershey Medical Center; Penn State Children's Hospital

🇺🇸

Hershey, Pennsylvania, United States

Froedtert Hospital

🇺🇸

Milwaukee, Wisconsin, United States

Akron Children's Hospital

🇺🇸

Akron, Ohio, United States

University of North Carolina at Chapel Hill

🇺🇸

Chapel Hill, North Carolina, United States

Childrens Hospital Los Angeles

🇺🇸

Los Angeles, California, United States

Indianapolis University Hospital; James Whitcomb Riley Hospital for Children

🇺🇸

Indianapolis, Indiana, United States

John Hopkins University

🇺🇸

Baltimore, Maryland, United States

Cincinnati Children's Hospital Medical Center

🇺🇸

Cincinnati, Ohio, United States

University Hospital of Cleveland

🇺🇸

Cleveland, Ohio, United States

Baylor College of Medicine/Texas Children's Hospital

🇺🇸

Houston, Texas, United States

Seattle Children's Hospital

🇺🇸

Seattle, Washington, United States

Nation Wide Childrens Hospital

🇺🇸

Columbus, Ohio, United States

University of Washington Medical Center

🇺🇸

Seattle, Washington, United States

Children's Hospital of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh of UPMC

🇺🇸

Pittsburgh, Pennsylvania, United States

Lucile S. Packard Children's Hospital

🇺🇸

Palo Alto, California, United States

Ann & Robert H. Lurie Children's Hospital of Chicago

🇺🇸

Chicago, Illinois, United States

The University of Kansas Hospital

🇺🇸

Kansas City, Kansas, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Children's Hospital Boston

🇺🇸

Boston, Massachusetts, United States

Devon Children's Hospital at Spectrum Health

🇺🇸

Grand Rapids, Michigan, United States

Children's Mercy Hospital

🇺🇸

Kansas City, Missouri, United States

Cardinal Glennon Children's Medical Center

🇺🇸

Saint Louis, Missouri, United States

Dartmouth Hitchcock Medical Center

🇺🇸

Lebanon, New Hampshire, United States

Women and Children's Hospital of Buffalo

🇺🇸

Buffalo, New York, United States

Maria Fareri Children's Hospital; Westchester Medical Center

🇺🇸

Valhalla, New York, United States

Columbia University Medical Center

🇺🇸

New York, New York, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

University of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

St. Louis Children's Hospital

🇺🇸

Saint Louis, Missouri, United States

National Jewish Health

🇺🇸

Denver, Colorado, United States

Children's Hospital of Michigan

🇺🇸

Detroit, Michigan, United States

Oregon Health & Sciences University

🇺🇸

Portland, Oregon, United States

The Children's Hospital at Vanderbilt

🇺🇸

Nashville, Tennessee, United States

Primary Children's Hospital

🇺🇸

Salt Lake City, Utah, United States

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

The Children's Hospital Colarado

🇺🇸

Aurora, Colorado, United States

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