The Leaky Lung Test

A Novel Non-invasive Way to Measure Airway Epithelial Permeability in Human Subjects

This is a clinical trial designed to test the hypothesis that measuring the absorption and excretion of inhaled mannitol will provide a clinically useful marker of airway epithelial permeability in asthma.

Study Overview

• Status: Completed
• Conditions: Lung Diseases, Obstructive; Asthma; Allergy; Reactive Airway Disease
• Intervention / Treatment: Drug: Mannitol

Detailed Description

A cohort of subjects with asthma and healthy controls will be exposed to inhaled mannitol according to FDA approved protocols for bronchoprovocation. Mannitol will be measured in the bloodstream and urine and used to determine an airway permeability index. This is a proof of concept study and not a trial of new therapeutics.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria: Asthma The diagnosis of asthma will be based on a consistent history, physical exam, and previous physician diagnosis of asthma. Consistent historical features of asthma include episodic wheezing, shortness of breath, chest tightness, or cough, often precipitated by known environmental triggers (e.g. respiratory viral infection, exposure to pollen, exercise, or stress). Consistent physical findings of asthma include audible expiratory wheezing and findings of associated diseases (e.g. eczema, allergic rhinitis), although the physical exam may be normal in between asthma attacks. Subjects will need to be free of asthma symptoms at time of challenge testing. Most asthmatic subjects should demonstrate bronchial reactivity during the mannitol challenge test.

Inclusion criteria: Non-asthmatic controls Healthy control subjects will be recruited in order to define baseline values for serum and urine mannitol. Healthy control subjects will be defined by the lack of symptoms or physical findings of asthma or other allergic diseases (e.g. eczema, allergic rhinitis), and absence of any other chronic lung disease. Healthy subjects should also not demonstrate bronchial reactivity during a mannitol challenge test.

Exclusion Criteria:

1. >5 pack year history of tobacco use or active smoking.
2. Other chronic or active lung diseases (e.g. COPD, pulmonary fibrosis, lung cancer)
3. History of significant renal insufficiency of liver disease
4. Asthma subjects with severe disease according to NAEPP guidelines (e.g. severe ongoing symptoms despite high-dose inhaled or oral glucocorticoids)
5. Asthma subjects with a baseline FEV1<65% predicted
6. Asthma subjects unwilling or unable to withhold medications prior to testing
7. Pregnant women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Asthma; Subjects with asthma will be exposed to inhaled mannitol according to FDA approved protocols.	Drug: Mannitol; Subjects will be challenged with inhaled mannitol according to already approved protocols.; Other Names: Aridol for bronchoprovocation
Experimental: Controls; Healthy control subjects will be exposed to inhaled mannitol according to FDA approved protocols.	Drug: Mannitol; Subjects will be challenged with inhaled mannitol according to already approved protocols.; Other Names: Aridol for bronchoprovocation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Airway permeability index (Urinary clearance of mannitol overtime)	Urinary clearance of mannitol overtime	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absorption of mannitol (Absorption and clearance of mannitol from the bloodstream)	Absorption and clearance of mannitol from the bloodstream	6 hours

Collaborators and Investigators

• Sponsor: University of Rochester
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH); Pharmaxis
• Investigators: Principal Investigator: Steve N Georas, M.D., University of Rochester

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: December 1, 2014
• First Submitted That Met QC Criteria: December 2, 2014
• First Posted (Estimate): December 3, 2014

Study Record Updates

• Last Update Posted (Actual): January 4, 2018
• Last Update Submitted That Met QC Criteria: January 2, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Physiological Effects of Drugs; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Mannitol
• Other Study ID Numbers: RSRB00043414; R01HL122424 (U.S. NIH Grant/Contract)