Rare CFTR Mutation Cell Collection Protocol (RARE)

NCT03161808 | Recruiting

• 1 other identifier: RARE-OB-16
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

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

Outcome Measures

Primary Outcomes (4)

• The Number of samples collected from cystic fibrosis participants with rare CFTR mutations

  CFTR mutations will be confirmed. Once the mutations are confirmed as RARE study eligible mutations, the specimen(s) collected will be expanded, added to a specimen bank and made available to the research community for the evaluation of potential CFTR modulating agents.

  2-5 year observational period

• The number of nasal cells collected

  Nasal cells will be collected from all participants.

  2-5 year observational period

• Number of Blood samples

  Blood samples will be collected from all participants

  2-5 year observational period

• Number of rectal samples collected

  Rectal biopsy samples will be collected from all participants

  2-5 year observational period

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects with a diagnosis of CF who meet all of the inclusion and none of the exclusion criteria will be eligible for participation in this study.

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Significantly diseased distal rectal/GI tissue that could place the participant 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)
• Any of the following abnormal lab values at the study visit:
• i. Platelets \< 50 x 10\^3/µL ii. Hemoglobin \< 10 gm/dL iii. Hematocrit \< 30% iv. WBC \> 20 x 10\^3/µL v. Neutropenia (ANC \< 1.5 x 10\^3/µL) vi. Lymphopenia (absolute lymphocyte count \< 1.5 x 10\^3/µL) vii. PT/INR \> 1.5 viii. Other bleeding diathesis
• Positive pregnancy test (for female of childbearing potential) at the study visit.
• Breastfeeding (if patient opts to use sedation).
• 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.
• History of organ transplant.
• 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.
• 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.

Sponsors & Collaborators

• George Solomon: lead
• Cystic Fibrosis Foundation: collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Nasal epithelial cells and blood (to confirm CFTR genotype and to derive iPSCs) will be collected from all subjects; consent for whole genome sequencing analysis will be obtained

MeSH Terms

Conditions

Cystic Fibrosis

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

Central Study Contacts

Heather Y Hathorne, PhD

CONTACT

205-638-9568; hyhathorne@uabmc.edu

Justin A Anderson, MS

CONTACT

205-689-8573; justinanderson@uabmc.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: May 9, 2017
• First Posted: May 22, 2017
• Study Start: October 5, 2017
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: February 2, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)