Nasal Potential Difference (NPD) for the Diagnosis of Cystic Fibrosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Children's Hospital of Philadelphia
Sponsor:
Information provided by (Responsible Party):
Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT00589745
First received: December 27, 2007
Last updated: October 17, 2014
Last verified: October 2014
  Purpose

The purpose of this research study is to provide a novel method for the diagnosis of Cystic Fibrosis (CF). This protocol is designed to test the ability of the cells to regulate the movement of salt and water in people with features of CF in whom the diagnosis is not entirely clear. We will be studying these cells in the nose, by a technique called nasal transepithelial potential difference (NPD).


Condition Intervention
Cystic Fibrosis
Other: Nasal potential difference measurement

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Measurement of Transepithelial Nasal Potential Difference (NPD) for the Diagnosis of Cystic Fibrosis

Resource links provided by NLM:


Further study details as provided by Children's Hospital of Philadelphia:

Primary Outcome Measures:
  • The basis of analysis will be the NPD response patterns, which will be interpreted and classified by the PI, as consistent or inconsistent with the diagnosis of CF based on comparison with published standards. [ Time Frame: Every visit ] [ Designated as safety issue: No ]

Estimated Enrollment: 25
Study Start Date: September 2003
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Subjects being evaluated for CF
Subjects will be referred from physicians who are clinically concerned about the possibility of Cystic Fibrosis. Nasal potential difference measurement will be obtained to potentially help aid in diagnosis.
Other: Nasal potential difference measurement
Nasal potential difference measurement involves dripping small amounts of 5 test solutions into the anterior nostril. This is designed to test the ability of the cells to regulate the movement of salt and water in people with features of CF in whom the diagnosis is not entirely clear.
Other Name: NPD

Detailed Description:

Cystic Fibrosis (CF) is an autosomal recessive systemic disorder of exocrine glands and secretory epithelia. The disease results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene which cause a variety of abnormalities. CFTR is absent or dysfunctional in cystic fibrosis. Most of the defects in CFTR result in abnormal chloride ion transport and abnormally viscous mucus. Nasal epithelial CFTR function will be assessed by the NPD procedure.

NPD measurements are useful as a diagnostic tool in individuals with borderline or normal sweat chlorides, one or no identified CFTR mutations, and a clinical history suggestive of CF. The NPD has become the gold standard for detection and quantification of CFTR function in the airways. The assay has also served as an important endpoint since 1981. It has been used extensively and is standardized to assess the ability of new therapeutics in studies designed to replace, repair or restore defective ion transport in CF patients.

The assay basically involves dripping small amounts of the test solutions into the anterior nostril in order to measure uptake or secretion of sodium and chloride. There are five solutions required for the NPD measurement:

  • Solution #1: Buffered Ringers
  • Solution #2: Solution #1+Amiloride
  • Solution #3: Buffered Zero Chloride Solution + Amiloride
  • Solution #4: Solution #3 + Isoproterenol
  • Solution #5: Solution #4 + Adenosine 5'-Triphosphate-Disodium salt (ATP)

The Cystic Fibrosis Therapeutics Development Network (TDN) is a formal affiliation of CF Research Centers in the US. Two Standard Operating Procedures have been developed by the TDN for the NPD procedure and qualification of those performing the measurement.

Procedure Details:

Briefly, a series of stopcocks is configured to allow perfusion of the above solutions through the port at the tip of an exploring catheter (PE50 tubing. All test solutions are perfused at a rate of 5.0 cc per minute. In each nostril, the PD readings in Ringer's at 0.5, 1.0, 1.5, 2, and 3 cm (lumen negative) are averaged and taken as the average 'baseline' PD. The catheter tip is then placed at the most negative PD site and maintained for superperfusion measurements with a small piece of tape applied to the nasal tip (to hold the catheter for the duration of the protocol). All solutions are warmed to 37˚C prior to contact with the nasal mucosa.

For each perfusion condition, a steady-state recording is obtained. The recording lasts at least one minute (for Solution #1) and for three minutes (for Solutions #2, 3, and 4) prior to proceeding to the next solution within the sequence. Solution #5 is perfused for a minimum of one minute, and confirms retention of ATP-activated Clˉ secretion in both CF and non-CF individuals. Several readings are obtained for data analysis, and then all nasal P.D. tracings are scored by investigators.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All ethnic groups accepted
  • Individuals with borderline or normal sweat chloride, one or no identified CFTR mutations and a clinical history suggestive of CF.
  • Children less than 6-8 years of age may be unable to cooperate (hold still) for the procedure, or be frightened by the procedure. Sedation may be necessary for performance of the procedure on a young child

Exclusion Criteria:

  • n/a
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00589745

Contacts
Contact: Christina Kubrak, RRT, CCRC 1-267-426-5135 kubrak@email.chop.edu

Locations
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Children's Hospital of Philadelphia
Investigators
Principal Investigator: Ronald Rubenstein, M.D., PhD. Children's Hospital of Philadelphia
  More Information

No publications provided

Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT00589745     History of Changes
Other Study ID Numbers: 1998-9-1589
Study First Received: December 27, 2007
Last Updated: October 17, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Children's Hospital of Philadelphia:
Diagnosis

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lung Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on October 28, 2014