Nasal Potential Studies Utilizing Cystic Fibrosis Transmembrane Regulator (CFTR) Modulators

NCT01348204 | Completed Phase 2 DMC

• 1 other identifier: F100107002
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to develop new biomarkers for studies of cystic fibrosis (CF). Defects in the gene encoding Cystic Fibrosis Transmembrane Regulator (CFTR) cause CF, an autosomal recessive disorder affecting mainly the pulmonary and digestive tract, leading to early death largely due to progressive loss of pulmonary function. In vitro experiments show that quercetin - a dietary supplement with a well-established safety profile for human use, including clinical trials in a variety of disorders encompassing cancer, heart disease, and as an anti-inflammatory agent - induces activation of CFTR. The nasal potential difference (NPD) test is a measurement of voltage across the nasal membrane and as a fundamental biomarker for CFTR activity in vivo. The NPD is a useful, well-established tool in CF research to determine both diagnoses as well as to measure the effect of new therapies. In vitro experiments show that quercetin induces activation of CFTR additive to that seen with current NPD reagents. In addition, it activates rescued mutant CFTR in vitro (∆F508 CFTR the most common cause of CF), whereas conventional agonists do not. Preliminary in vivo experiments mirrored these results and show that quercetin activates CFTR in human (n=12) NPD tests. Importantly, quercetin perfusion was well-tolerated by a validated sinus questionnaire and physician assessed nasal examination rating. These studies provide strong support for use of quercetin as potentiator of CFTR Cl- channel function by nasal administration. By adding quercetin to the sequence of perfusion solutions for NPD, the investigators may be better suited to detect ∆F508 CFTR activity of rescued mutant protein in the CF patient population.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• NPD Biomarker

  Determine whether the NPD biomarker can be improved by including the potentiator quercetin to activate CFTR dependent ion channel activity among CF individuals with surface localized CFTR mutations

  patients enroll for a single 2-4 hour visit

Secondary Outcomes (1)

• Residual CFTR activity

  patients enroll for a single 2-4 hour visit

Study Arms (1)

quercetin

EXPERIMENTAL

health food supplement

Other: quercetin

Interventions

quercetin OTHER

health food supplement

quercetin

Eligibility Criteria

• Age: 8 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• years old
• absence of pulmonary exacerbation in the last 2 weeks
• willingness to perform nasal potential difference measurement

You may not qualify if:

• Need for chronic oxygen supplementation
• positive for B. cepecia within the last year
• active participation in another interventional trial utilizing ion transport modulators
• interfering medical conditions
• pregnant females

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Quercetin

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

Intervention Hierarchy (Ancestors)

Flavonols; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Steven M Rowe, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 1, 2010
• First Posted: May 5, 2011
• Study Start: March 1, 2010
• Primary Completion: June 1, 2011
• Study Completion: November 1, 2011
• Last Updated: January 31, 2012

Record last verified: 2012-01

Locations

US (1)