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

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

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).

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Other: Nasal potential difference measurement

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: 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 Names: NPD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	Every visit

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start: September 1, 2003
• Primary Completion (ACTUAL): December 18, 2019
• Study Completion (ACTUAL): December 18, 2019

Study Registration Dates

• First Submitted: December 27, 2007
• First Submitted That Met QC Criteria: January 9, 2008
• First Posted (ESTIMATE): January 10, 2008

Study Record Updates

• Last Update Posted (ACTUAL): January 29, 2020
• Last Update Submitted That Met QC Criteria: January 27, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Diagnosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: 98-001589