Ivacaftor for Acquired CFTR Dysfunction in Chronic Rhinosinusitis

• Status: Recruiting
• Trial end date: 2024-05-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this pilot study is to explore wither ivacaftor in refractory CRS patients will demonstrate safety and tolerability; restore CFTR-mediated Cl- secretions as measured by EDSPD testing; produce detectable improvements in validated measures of CRS including the SNOT-22 questionnaire, Lund-MacKay CT scan grading, and Lund-Kennedy endoscopic scores; and provide beneficial effects on readily measured markers of sinonasal inflammation and infection (IP-10, IL-8, and Pseudomonas CFUs).

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Alabama at Birmingham
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Anti-Bacterial Agents; Ivacaftor

Criteria

Inclusion Criteria:

• 18 years of age

• Patient has provided informed consent

• Diagnosis of CRS made by one of the investigators

• Standard of care CT scan with definitive demonstration of isolated or diffuse mucosal thickening, bone changes, and air fluid levels, obtained within 30 days of treatment

• Positive culture of at least one gram negative bacteria (e.g. Pseudomonas, E. coli, Steenotrophomonas) within 30 days prior to testing

• Previous surgery with (at least) exposed maxillary and ethmoid sinuses

• Ability to perform EDSPD testing such that nasal cavity space and sinus openings are sufficient for catheter placement

• Negative pregnancy test for females of childbearing potential within 72 hours of testing and start of study treatment

Exclusion Criteria:

• < 18 years of age

• Acute illness other than sinusitis within 2 weeks before start of study treatment that, in the opinion of the investigator, would preclude participation

• Currently taking medications that are moderate or strong CP3A inhibitors

• History of asthma attack requiring emergency room visit or treatment with oral steroids within 2 months prior to study treatment

• History of solid organ or hematological transplantation

• History of known immunodeficiency, autoimmune or granulomatous disorder

• Serum creatinine > 1.5x upper normal limit

• Abnormal liver function, as defined by serum AST > 2x upper normal limit, serum ALT > 2x upper normal limit, Alkaline phosphatase > 2x upper normal limit, Total bilirubin > 2x upper normal limit

• Women who are pregnant or breastfeeding