Nasal Potential Difference (NPD) Protocol in Chronic Rhinosinusitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02038166
Recruitment Status : Recruiting
First Posted : January 16, 2014
Last Update Posted : September 19, 2018
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Brad Woodworth, MD, University of Alabama at Birmingham

Brief Summary:
The purpose of this study is to determine if acquired (partial) Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) deficiency contributes substantially to the pathogenic mechanisms underlying Chronic Rhinosinusitis (CRS), creating a localized environment that impairs mucociliary clearance (MCC).

Condition or disease

Detailed Description:

Nasal Potential Difference (NPD) measurements will be conducted on participants. The NPD measurement, is a bioelectric assay of CFTR-dependent ion transport that has been used in a variety of protocols designed to detect CFTR function. A 4-Step protocol will be utilized. The nasal cavities will be perfused in a step-wise fashion with the following solutions: 1) Ringer's solution, 2) Ringer's solution + amiloride 100μM, 3) Low-Cl--containing solution, and 4) Low-Cl- + isoproterenol (10 µM). The potential difference will be monitored in nasal epithelium in comparison to an agar filled reference butterfly electrode placed in the volar aspect of the forearm, and connected via a calomel cell to a high impedance voltmeter.

Following placement of the subcutaneous reference bridge, the nasal probe will be secured 1-3 cm within the inferior meatus and secured in position at the most polarizing position. Each nare will then be sequentially perfused with Ringer solution. All nasal potential difference tracings will be scored independently by a single reviewer.

The investigator and an internal committee comprised of Gregory Fleming James Associate Scientists will oversee the safety of the study. Our internal committee is a multidisciplinary group consisting of physician and subspecialists who, collectively, have experience in treatment patients with cystic fibrosis and other airway disease in the conduct of randomized clinical trials. The primary responsibility of this committee is to protect the safety and welfare of subjects consenting to the investigator's procurement of remnant tissue during endoscopic sinus procedure. Members are responsible for reviewing procedural conduct, including acquisition of consents and materials, to protect patient well-being. An interim data safety review will be conducted on a yearly basis. The committee will consist of at least 3 members with clinical trials experience in airway diseases. During annual review, issues relating to the safety and process for acquiring human tissues will be reviewed. Summary reports from each annual meeting will be prepared and will address concerns about the procurement of tissue or any other information deemed pertinent to the review.

Study Type : Observational
Estimated Enrollment : 20 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Chloride Secretagogues for Acquired CFTR Dysfunction in Chronic Rhinosinusitis (NPD Protocol)
Study Start Date : January 2015
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : December 2019

Primary Outcome Measures :
  1. Measurable Difference in CFTR function [ Time Frame: One Year ]
    A >-5 mV increase in total chloride secretion (change in NPD following nominal Cl- solution + amiloride + isoproterenol) is typically designated as evidence of measurable difference in CFTR function. Results of NPD measurements between CRS patients and healthy controls will be examined.

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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients presenting to UAB for evaluation of CRS

The patient eligibility criteria are designed to limit enrollment to healthy individuals and patients who clearly have CRS based on Sinus and Allergy health partnership criteria, but who are sufficiently well (both in terms of CRS and in terms of concomitant illness, such as asthma) to safely participate in study procedures and provide interpretable results.

Inclusion Criteria:

a. Patients with CRS will be diagnosed according to Sinus and Allergy Health Partnership symptom-based and objective criteria as follows: i. Duration of disease is qualified by continuous symptoms (≥ 2 major factors or at least 1 major factor & 2 minor symptoms; Table 2) for ≥ 12 consecutive weeks or ≥ 12 weeks of physical findings. ii. One of these signs of inflammation must be present and identified in association with ongoing symptoms.

  1. Discolored nasal drainage arising from the nasal passages, nasal polyps, or polypoid swelling as identified on physical examination with nasal endoscopy.
  2. Edema or erythema of the middle meatus or ethmoid bulla
  3. Generalized or localized erythema or edema. If it does not involve the middle meatus or ethmoid bulla, CT scan is performed to confirm a diagnosis.
  4. The CT scan must demonstrate isolated or diffuse mucosal thickening, bone changes, air-fluid levels. b. Age ≥ 19 years and Weight ≥ 50 kg c. Ability to perform NPD testing d. Negative pregnancy test (for females of childbearing potential) e. Written informed consent

Exclusion Criteria:

  1. Acute illness within 2 weeks before start of study treatment.
  2. History of major asthma attack within 2 months prior to start of study treatment.
  3. Change in intranasal medications (including use of corticosteroids, cromolyn, atrovent, phenylephrine, or oxymetazoline) within 14 days prior to start of study treatment.
  4. Positive hepatitis B surface antigen, hepatitis C antibody test, or human immunodeficiency virus (HIV) test.
  5. Hemoglobin <10 gm/dL and Serum albumin <2.5 g/dL.
  6. Abnormal liver function (serum ALT, AST, alkaline phosphatase, or total bilirubin >2 times upper limit of normal).
  7. Abnormal renal function (serum creatinine >1.5 times upper limit of normal).
  8. Pregnancy or breast feeding.
  9. History of solid organ or hematological transplantation
  10. History of autoimmune or granulomatous disorder.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02038166

Contact: Lisa Clemons, MSN, RN (205) 934-9714

United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35244
Sponsors and Collaborators
University of Alabama at Birmingham
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Brad Woodworth, MD University of Alabama at Birmingham

Responsible Party: Brad Woodworth, MD, Associate Professor of Surgery, University of Alabama at Birmingham Identifier: NCT02038166     History of Changes
Other Study ID Numbers: F100930005
1K08HL107142-01 ( U.S. NIH Grant/Contract )
First Posted: January 16, 2014    Key Record Dates
Last Update Posted: September 19, 2018
Last Verified: September 2018

Additional relevant MeSH terms:
Paranasal Sinus Diseases
Nose Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases