Rare CFTR Mutation Cell Collection Protocol (RARE)

Description

Over 1,900 mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein are implicated in causing Cystic Fibrosis (CF). Potential therapies that directly target defective CFTR are being evaluated in important clinical trials, but most target the most common CFTR mutation F508del. Many patients with rare CF mutations are not able to participate in those studies. The RARE study is specifically designed for people with CF caused by rare mutations. Eligible rare mutations are listed below: • CF patients who are heterozygous for pre-mature stop codons as noted below: i. one allele must be a F508del ii. the other allele must be a pre-mature stop codon mutation • CF Patients with other genotypes that require Study PI permission: i. CF patients with two mutations that are not eligible for Trikafta ii. CF patients homozygous or heterozygous (other allele must be F508del) for rare mutations of special interest (e.g., 711+3A-\>G, 2789+5G-\>A, 3272-26A-\>G, 3849+10kbC-\>T). Other rare mutations will be considered on a case by case basis This is a multi-site, specimen collection study. Investigators will collect blood, intestinal cells and nasal cells from each participant. Cells from these specimens will be used to test future CFTR modulators to see if they might work for people with study eligible rare mutations. Having cells to test in the lab is an important first step in identifying potential new therapies for people with these mutations.

Conditions

Cystic Fibrosis

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Study Overview

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Study Details

Study overview

Over 1,900 mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein are implicated in causing Cystic Fibrosis (CF). Potential therapies that directly target defective CFTR are being evaluated in important clinical trials, but most target the most common CFTR mutation F508del. Many patients with rare CF mutations are not able to participate in those studies. The RARE study is specifically designed for people with CF caused by rare mutations. Eligible rare mutations are listed below: • CF patients who are heterozygous for pre-mature stop codons as noted below: i. one allele must be a F508del ii. the other allele must be a pre-mature stop codon mutation • CF Patients with other genotypes that require Study PI permission: i. CF patients with two mutations that are not eligible for Trikafta ii. CF patients homozygous or heterozygous (other allele must be F508del) for rare mutations of special interest (e.g., 711+3A-\>G, 2789+5G-\>A, 3272-26A-\>G, 3849+10kbC-\>T). Other rare mutations will be considered on a case by case basis This is a multi-site, specimen collection study. Investigators will collect blood, intestinal cells and nasal cells from each participant. Cells from these specimens will be used to test future CFTR modulators to see if they might work for people with study eligible rare mutations. Having cells to test in the lab is an important first step in identifying potential new therapies for people with these mutations.

Rare CFTR Mutation Cell Collection Protocol (RARE)

Rare CFTR Mutation Cell Collection Protocol (RARE)

Condition
Cystic Fibrosis
Intervention / Treatment

-

Contacts and Locations

Birmingham

University of Alabama at Birmingham, Birmingham, Alabama, United States, 35233

Palo Alto

Lucile S. Packard Children's Hospital, Palo Alto, California, United States, 94394

Aurora

Children's Hospital Colorado, Aurora, Colorado, United States, 80045

Minneapolis

University of Minnesota Medical Center, Fairview, Minneapolis, Minnesota, United States, 55455

New York

Morgan Stanley Children's Hospital of New York, New York, New York, United States, 10032

Cincinnati

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States, 45229

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • * Male or female ≥ 12 years of age at time of consent
  • * Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with CF and one or more of the following criteria (1. Sweat chloride ≥ 60 milliequivalents/Liter (mEq/L) by quantitative pilocarpineiontophoresis test (QPIT) OR upon permission of the RARE Investigator- Sponsors, 2. Two well-characterized mutations in the cystic fibrosis transmembrane conductive regulator (CFTR) gene, 3.Abnormal nasal potential difference (NPD) (change in NPD in response to a low chloride solution and isoproterenol of lessthan -6.6 mV)
  • * Confirmed genotype of the current recruitment focus for certain target rare mutations. The initial recruitment focus will be CF patients who are homozygous for pre-mature stop codons. Operations Memos will detail any future current genotype targets.
  • * Written informed consent (and assent when applicable) obtained from participant or participant's legal representative and ability to comply with the requirements of the study.
  • * Willing to travel (if needed) to a regional study site for cell collection.
  • 1. Presence of a medical condition, abnormality, or laboratory value(s) that in the opinion of the onsite principal investigator and/or collaborating gastroenterologist may compromise the quality of the data or place the subject at significant risk by undergoing the research related biopsy, including:
  • 2. Positive pregnancy test (for female of childbearing potential) at the study visit.
  • 3. Breastfeeding (if patient opts to use sedation).
  • 4. Current use of drugs with significant risks of compromising immunity (e.g. oral steroid use \>20 mg/day) for \>14 days prior to the rectal biopsy.
  • 5. History of organ transplant.
  • 6. Use of oral anticoagulant medications (e.g., chronic anticoagulant therapy such as warfarin or platelet inactivators such as aspirin) within seven days prior to rectal biopsy.
  • 7. Unable or unwilling to withhold use of oral anticoagulant medications (e.g., chronic anticoagulant therapy such as warfarin or platelet inactivators such as aspirin) within 7 days after rectal biopsy.

Ages Eligible for Study

12 Years to

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

George Solomon,

Study Record Dates

2024-12-01