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

NCT02477319 | Completed Results

• 1 other identifier: PROSPECT
• Study Type: observational
• Target: 452
• Locations: 1 country
• Sites: 38

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

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (2)

• Sweat Chloride by Cohort (Part A Only)

  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.

  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.

• 6 Month Change in FEV1 Percent Predicted (Part B Only)

  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.

  Baseline and 6 months

Study Arms (2)

Part A

* Cohort 1: Healthy Controls * Cohort 2: Partial CFTR function CF (class IV/V) * Cohort 3: Absent CFTR function CF (Class I/II)

Other: Observational

Part B

CF patients who are homozygous for the F508del

Other: Observational

Interventions

Observational OTHER

Part A; Part B

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Part A N = 260 (210 CF, 50 non-CF controls) * Cohort 1: 50 non-CF control subjects ≥ 12 years of age, with at least 15 subjects 12 - 21 yrs of age * Cohort 2: 50 Partial CFTR Function CF subjects with at least one class IV/V CFTR mutation, ≥ 12 years of age * Cohort 3 160 Absent CFTR Function CF subjects with two class I/II mutations ≥ 12 years of age Part B Up to 250 CF subjects who are homozygous for F508del mutation and who are prescribed ivacaftor/lumacafor for clinical care will be allowed to enroll. This will include : * Cohort 3 subjects homozygous for F508del mutation from Part A who are prescribed ivacaftor/lumacaftor will be invited to participate in Part B (up to 100 potential subjects). * Up to 150 additional CF subjects homozygous for F508del mutation ≥ 12 years of age who did not participate in Part A but are otherwise eligible for participation in Part B.

You may qualify if:

• \. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative.
• \. Be willing and able to adhere to the study visit schedule and other protocol requirements 3. Male or female ≥ 12 years of age at Visit 1. 4. Have a body mass index (BMI) of:
• For subjects ≥ 18 years of age: ≤ 30 kg/m2
• For subjects 12 - 17 years of age: ≤ 95th percentile 5. Be a non-smoker for ≥ 1 year at screening and have ≤ 10 pack-year history of smoking.
• \. To participate in the optional DNA banking component of this study, subject must have signed the informed consent indicating willingness to participate in the genomic component of the study. Refusal to give consent for this component does not exclude a subject from participation in the study.
• Written informed consent (and assent when applicable) obtained from subject or subject's legal representative.
• Male or female ≥ 12 years of age at Visit 1.
• Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and the following criteria: Cohort 2: (Partial Function CFTR CF)
• Two mutations in the CFTR gene:
• At least one allele must be a Class IV or V mutation
• The second allele can be within any CFTR mutation class.
• Pancreatic sufficient (based on the absence of daily PERT use)
• At least one historic sweat chloride ≥60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT) OR sweat chloride results ≥ 40, but \< 60mEQ/L upon permission of the PROSPECT Investigator-Sponsors.
• Cohort 3: (Absent Function CF)
• Two class I or II CFTR mutations

You may not qualify if:

• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
• A history of any clinically significant medical illness or medical disorder that requires ongoing systemic medical therapy, including (but not limited to) cardiovascular disease, neuromuscular disease, hematological disease including bleeding disorders, chronic respiratory disease (including persistent asthma), hepatic or gastrointestinal (GI) disease, neurological disease, neoplastic disease, renal diseases, or endocrine disorders including diabetes.
• Acute illness requiring any new prescription or over-the-counter treatment within 14 days prior to Visit 1.
• Major or traumatic surgery within 12 weeks prior to Visit 1.
• For females of child-bearing potential: a positive pregnancy test at Visit 1.
• Initiation of any new chronic therapy within 28 days prior to Visit 1.
• Use of an investigational agent within 28 days prior to Visit 1.
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
• Initiation of newly prescribed antibiotics \[oral, intravenous (IV), and/or inhaled\] for acute respiratory symptoms within 2 weeks of Visit 1.
• Major or traumatic surgery within 12 weeks prior to Visit 1.
• For females of child-bearing potential: a positive pregnancy test at Visit 1.
• Initiation of any new chronic therapy (e.g., ibuprofen Pulmozyme®, hypertonic saline, azithromycin, TOBI®, Cayston®) within 4 weeks prior to Visit 1.
• Use of an investigational agent within 28 days prior to Visit 1.
• Use of oral corticosteroids in doses exceeding 10 mg prednisone/day or 20 mg prednisone/every other day (subjects on oral steroids will be on stable doses for \> 12 weeks prior to visit 1).
• Active treatment for nontuberculous mycobacterial (NTM) infection, consisting of ≥ two antibiotics (oral, IV, and/or inhaled).

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Cystic Fibrosis Foundation: collaborator

Study Sites (38)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Childrens Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Lucile S. Packard Children's Hospital

Palo Alto, California, 94394, United States

Location

The Children's Hospital Colarado

Aurora, Colorado, 80045, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

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

Chicago, Illinois, 60611-2605, United States

Location

Indianapolis University Hospital; James Whitcomb Riley Hospital for Children

Indianapolis, Indiana, United States

Location

The University of Kansas Hospital

Kansas City, Kansas, 66160, United States

Location

John Hopkins University

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

Devon Children's Hospital at Spectrum Health

Grand Rapids, Michigan, 49503, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Cardinal Glennon Children's Medical Center

St Louis, Missouri, 63104, United States

Location

St. Louis Children's Hospital

St Louis, Missouri, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Location

Women and Children's Hospital of Buffalo

Buffalo, New York, 14222, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Maria Fareri Children's Hospital; Westchester Medical Center

Valhalla, New York, 10595, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

University Hospital of Cleveland

Cleveland, Ohio, 44106, United States

Location

Nation Wide Childrens Hospital

Columbus, Ohio, United States

Location

Oregon Health & Sciences University

Portland, Oregon, 97239, United States

Location

Hershey Medical Center; Penn State Children's Hospital

Hershey, Pennsylvania, 17033, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29403, United States

Location

The Children's Hospital at Vanderbilt

Nashville, Tennessee, 37232-9500, United States

Location

Baylor College of Medicine/Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84132, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98145-9807, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 55455, United States

Location

Related Publications (1)

• Sagel SD, Khan U, Heltshe SL, Clancy JP, Borowitz D, Gelfond D, Donaldson SH, Moran A, Ratjen F, VanDalfsen JM, Rowe SM. Clinical Effectiveness of Lumacaftor/Ivacaftor in Patients with Cystic Fibrosis Homozygous for F508del-CFTR. A Clinical Trial. Ann Am Thorac Soc. 2021 Jan;18(1):75-83. doi: 10.1513/AnnalsATS.202002-144OC.

  PMID: 32644818 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Watchful Waiting

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Results Point of Contact

• Title: Umer Khan (Principal Biostatistician)
• Organization: Seattle Children's Hospital

umer.khan@seattlechildrens.org

206-884-7516

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 22, 2015
• First Posted: June 22, 2015
• Study Start: March 1, 2015
• Primary Completion: April 25, 2018
• Study Completion: July 27, 2018
• Last Updated: May 20, 2020
• Results First Posted: May 20, 2020

Record last verified: 2020-05

Locations

US (38)