Clinical trial NCT01078740: Detection of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Activity in Rectal Tissues From Human Subjects
Official title: Detection of Cystic Fibrosis Transmembrane Conductance Regulator CFTR) Activity in Rectal Tissues From Human Subjects
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cystic Fibrosis
Keywords: cystic fibrosis
cystic fibrosis transmembrane conductance regulator
biomarkers
Intestinal Current Measurement
Lead sponsor: CF Therapeutics Development Network Coordinating Center
Sponsor class: NETWORK
Collaborators: name: Cystic Fibrosis Foundation
First posted: 2010-03-02
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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 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)

Primary outcomes:
measure: 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).
timeFrame: 24 hours
Secondary outcomes:
measure: To estimate the range of detectable CFTR activity among human rectal tissue of subjects with and without cystic fibrosis.
timeFrame: 24 hours
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Hospital
state: Alabama
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Chapel Hill
country: United States
facility: University of North Carolina Hospitals
state: North Carolina
Study officials:
affiliation: University of Alabama at Birmingham
name: JP Clancy, MD
role: PRINCIPAL_INVESTIGATOR
References: