Rare CFTR Mutation Cell Collection Protocol (RARE)

This is a single-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 the study site (UAB) 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 research coordinator can provide more detail on how much participants will be paid.
• This study is being conducted at UAB

Visit Schedule:

Two day study visit

Inclusion criteria

• Male or female ≥ 17 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

• 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.