Rare CFTR Mutation Cell Collection Protocol (RARE) (RARE)

• ClinicalTrials.gov Identifier: NCT03161808
• Recruitment Status: Recruiting
• First Posted: May 22, 2017
• Last Update Posted: August 26, 2022
• Sponsor: George Solomon
• Collaborator: Cystic Fibrosis Foundation
• Information provided by (Responsible Party): George Solomon, University of Alabama at Birmingham

Study Description

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.

Condition or disease
Cystic Fibrosis

Detailed Description:

This is a multi-site, specimen collection study for people with Cystic Fibrosis who have rare mutations. This study is non-interventional so there is no study drug or investigational treatment involved.

• Once a potentially eligible participant is identified (either self-identified or by their CF care center), and the person has expressed interest in participating in the study, the participant will be referred to a participating study site to receive additional information about the study and about travel arrangements (if needed).
• The eligibility criteria are broad and inclusive: Often studies have restrictions around lung function that limit who can participate. The only real restriction for this study rare mutations as defined on the RARE study eligible mutations list.
• Blood, intestinal cells, nasal cells will be collected from all participants.
• Participants will be compensated for the time of the visit and travel expenses will be pre-paid by the study. The study site research coordinator can provide more detail on how much participants will be paid.
• This study is being conducted at six regional sites. Participants may travel to any of the regional study sites to participate, but the participant will need to talk with the research coordinator at the site of their choice to get all of the study details before making a decision to participate. The study site research coordinator will put participants in contact with the travel agency to arrange and pre-pay for travel (including hotel, airline/train arrangements as needed).

Visit Schedule:

Two day study visit

Study Design

• Study Type: Observational
• Estimated Enrollment: 500 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Rare CFTR Mutation Cell Collection Protocol (RARE)
• Actual Study Start Date: October 5, 2017
• Estimated Primary Completion Date: December 1, 2024
• Estimated Study Completion Date: December 1, 2024

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. The Number of samples collected from cystic fibrosis participants with rare CFTR mutations [ Time Frame: 2-5 year observational period ]
   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. The number of nasal cells collected [ Time Frame: 2-5 year observational period ]
   Nasal cells will be collected from all participants.
3. Number of Blood samples [ Time Frame: 2-5 year observational period ]
   Blood samples will be collected from all participants
4. Number of rectal samples collected [ Time Frame: 2-5 year observational period ]
   Rectal biopsy samples will be collected from all participants

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

Eligibility Criteria

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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.

Criteria

Inclusion 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.

Exclusion Criteria:

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:

   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

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.

Contacts and Locations

Contacts

Contact: Heather Y Hathorne, PhD; 205-638-9568; hyhathorne@uabmc.edu

Contact: Justin A Wade, BS; 205-638-9188; jdwade@uabmc.edu

Locations

United States, Alabama

University of Alabama at Birmingham; Recruiting

Birmingham, Alabama, United States, 35233

Contact: Heather Hathorne, PhD, CCRC 205-639-9568 hyhathorne@uabmc.edu

Contact: Jonathan Y Bergeron, BS 205-638-2220 jbergeron@uabmc.edu

Principal Investigator: George M Solomon, MD

United States, California

Lucile S. Packard Children's Hospital; Recruiting

Palo Alto, California, United States, 94394

Contact: Lani Demchak 650-725-1087 lldemchak@stanford.edu

United States, Colorado

Children's Hospital Colorado; Recruiting

Aurora, Colorado, United States, 80045

Contact: Allison Keck 720-777-0734 Allison.Keck@childrenscolorado.org

United States, Minnesota

University of Minnesota Medical Center, Fairview; Recruiting

Minneapolis, Minnesota, United States, 55455

Contact: University of Minnesota, Participant Contact University of Minnesota, Participant Contact cftrials@umn.edu

United States, New York

Morgan Stanley Children's Hospital of New York; Recruiting

New York, New York, United States, 10032

Contact: Hossein Sadeghi 212-305-5122 HS762@cumc.Columbia.edu

United States, Ohio

Cincinnati Children's Hospital Medical Center; Recruiting

Cincinnati, Ohio, United States, 45229

Contact: Rachel Sobkowiak 513-803-0762 Rachel.Sobkowiak@cchmc.org

Sponsors and Collaborators

George Solomon

Cystic Fibrosis Foundation

More Information

• Responsible Party: George Solomon, MD, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT03161808
• Other Study ID Numbers: RARE-OB-16
• First Posted: May 22, 2017
• Last Update Posted: August 26, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Cystic Fibrosis; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases