Detection of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Activity in Rectal Tissues From Human Subjects

This study has been completed.
Sponsor:
Collaborator:
Cystic Fibrosis Foundation
Information provided by (Responsible Party):
CF Therapeutics Development Network Coordinating Center
ClinicalTrials.gov Identifier:
NCT01078740
First received: February 26, 2010
Last updated: March 5, 2013
Last verified: March 2013
  Purpose

This is a pilot study. The purpose of the study is to facilitate the development of a new biomarker of cystic fibrosis transmembrane conductance regulator (CFTR) function using rectal tissue.


Condition
Cystic Fibrosis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Detection of Cystic Fibrosis Transmembrane Conductance Regulator CFTR) Activity in Rectal Tissues From Human Subjects

Resource links provided by NLM:


Further study details as provided by CF Therapeutics Development Network Coordinating Center:

Primary Outcome Measures:
  • To develop and improve techniques to detect mature CFTR protein at the rectal cell membrane by performing rectal biopsies and ex-vivo Intestinal Current Measurement (ICM). [ Time Frame: 24 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To estimate the range of detectable CFTR activity among human rectal tissue of subjects with and without cystic fibrosis. [ Time Frame: 24 hours ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Rectal biopsy


Enrollment: 57
Study Start Date: October 2009
Study Completion Date: August 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts
Non-CF subjects
Rectal tissue obtained from study subjects without cystic fibrosis (CF) as part of scheduled colonoscopy/biopsies performed for clinical care
CF subjects

Rectal tissue obtained from study subjects with cystic fibrosis (CF) in one of three ways:

  • Rectal biopsy as part of scheduled colonoscopy/biopsies performed for clinical care
  • Sigmoidoscopy/biopsy added onto a scheduled, unrelated procedure or surgery performed under general anesthesia
  • Sigmoidoscopy/biopsy performed for the sole purpose of obtaining rectal tissue for the current study

Detailed Description:

CF research has advanced to the point where small molecule agents have been developed to overcome the underlying genetic defects caused by CFTR mutations.

There is a critical need to develop new sensitive biomarkers of CFTR function and biochemistry that can be used in early phase clinical trials to demonstrate biologic effects of investigative agents in vivo. Intestinal Current Measurement (ICM) from rectal biopsy samples is an assay that has been proven to be sensitive and specific for CFTR function. This method and site of investigation is particularly attractive, since CFTR is expressed at high levels in the rectum, it is not altered by disease manifestations, and the tissue can be studied ex vivo, providing more flexibility in the nature of the techniques to detect and quantify CFTR activity.

This study will aid in the development of new biomarkers in human rectal tissue for use in CF clinical trials. Testing compounds that are designed to restore function to disease-causing CFTR genes and proteins will provide an opportunity to improve and standardize techniques in the acquisition and measurement of CFTR activity in rectal biopsy specimens.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Non-CF subjects: Adults undergoing endoscopic procedures (colonoscopies) who meet the eligibility criteria.

CF subjects: Adults with a diagnosis of CF who meet the eligibility criteria. CF subjects can include both patients who will be undergoing endoscopic (colonoscopies) and nonendoscopic procedures requiring anesthesia or sedation as a part of clinical care (e.g., sinus surgery, central line placement), or CF subjects not undergoing planned surgical/anesthetic procedures.

Criteria
  1. Non-CF subjects

    Inclusion Criteria:

    • Male or female 18-75 years of age at enrollment
    • Undergoing colonoscopy for clinical care
    • Written informed consent obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study

    Exclusion Criteria:

    • Any medical condition or laboratory values that in the opinion of the onsite principal investigator and/or collaborating gastroenterologist may place the subject at significant risk by undergoing the additional research related biopsies
    • Subjects with a history of radiation therapy to the rectum, prostate and/or pelvic area
  2. CF subjects undergoing a surgical procedure for clinical care

    Inclusion Criteria:

    • Confirmed diagnosis of CF based on the following criteria: ∆F508 homozygous
    • Male or female 18 years of age or greater at enrollment
    • Patient undergoing planned colonoscopy or other surgical procedure and agrees to undergo sigmoidoscopy and biopsy
    • Written informed consent obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study

    Exclusion Criteria:

    Any medical condition or laboratory values that in the opinion of the onsite principal investigator and/or collaborating gastroenterologist may place the subject at significant risk by undergoing the additional research related biopsies, including:

    • Significantly diseased distal rectal/gastrointestinal (GI) tissue (as judged by the collaborating gastroenterologist including radiation injury or history of radiation therapy to the rectum, prostate and/or pelvic area
    • Significant hemorrhoids or vascular abnormalities (as judged by the collaborating gastroenterologist)
    • Significant colonic infection (as judged by the collaborating gastroenterologist)
  3. CF subjects undergoing sigmoidoscopy biopsy procedure for study purposes only

Inclusion Criteria:

  • Confirmed diagnosis of CF based on the following criteria: ∆F508 homozygous
  • Male or female 18 years of age or greater at enrollment
  • Written informed consent obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study
  • CBC, PT/PTT within acceptable range (see exclusion criteria for values) within 14 days of the procedure
  • Negative pregnancy test (if applicable) completed within two (2) days of the procedure

Exclusion Criteria:

Any medical condition or laboratory values that in the opinion of the onsite principal investigator and/or collaborating gastroenterologist may place the subject at significant risk by undergoing the additional research related biopsies, including:

  • Bleeding diathesis (platelets <50,000, INR >1.5)
  • Anemia (hemoglobin <10 gm/dL, or hematocrit <30%
  • White blood count >20,000
  • Neutropenia (ANC <1,500) or lymphopenia (absolute lymphocyte count <1,500)
  • Positive pregnancy test (if applicable)
  • Breastfeeding
  • Significantly diseased distal rectal/GI tissue that could place the study subject at risk by participating in the study (as judged by the collaborating gastroenterologist, such as significant hemorrhoids, vascular abnormalities, colonic infection, radiation injury or history of radiation therapy to the rectum, prostate and/or pelvic area)
  • Use of drugs with significant risks of compromising immunity (oral steroid use > 20 mg/day)
  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: NCT01078740

Locations
United States, Alabama
University of Alabama at Birmingham Hospital
Birmingham, Alabama, United States, 35249
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, North Carolina
University of North Carolina Hospitals
Chapel Hill, North Carolina, United States, 27514
Sponsors and Collaborators
CF Therapeutics Development Network Coordinating Center
Cystic Fibrosis Foundation
Investigators
Principal Investigator: JP Clancy, MD University of Alabama at Birmingham
  More Information

No publications provided

Responsible Party: CF Therapeutics Development Network Coordinating Center
ClinicalTrials.gov Identifier: NCT01078740     History of Changes
Other Study ID Numbers: ICM001
Study First Received: February 26, 2010
Last Updated: March 5, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by CF Therapeutics Development Network Coordinating Center:
cystic fibrosis
cystic fibrosis transmembrane conductance regulator
biomarkers
Intestinal Current Measurement

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

ClinicalTrials.gov processed this record on July 28, 2014