search
Back to results

Elucidation of Acid-Induced Pulmonary Inflammation

Primary Purpose

Gastroesophageal Reflux, Asthma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
lansoprazole
placebo
Sponsored by
University of Utah
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastroesophageal Reflux

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: chronic cough consistent with bronchoreactivity Gastroesophageal reflux Exclusion Criteria: Severe asthmatics who have been hospitalized within the last 6 months or who have required oral steroid use within the last 4 weeks Severe coronary artery disease Cigarette/cigar smoking within the last 6 months Documented allergies affecting the respiratory system Subjects with contraindications to pH/impedance probe Hemophilia Septal deviation Subjects with contraindications to bronchoscopy as outlined by the American Thoracic Society Guidelines Anticoagulation Pregnancy Incarcerated patients Current oral steroid use (may suppress levels of inflammation) Upper respiratory infection within the last 2 weeks Ongoing acid suppression with a proton pump inhibitor, however, patients may be included if they have discontinued their proton pump inhibitor within the last 1 month with stable asthma symptoms as defined by stable utilization of inhaled steroids

Sites / Locations

  • University of Utah Health Sciences Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Lansoprazole therapy

Placebo

Arm Description

Lansoprazole 30 mg orally twice daily

placebo orally twice daily

Outcomes

Primary Outcome Measures

Change in Lymphocyte Count
Change in mean lymphocyte count in bronchus intermedius biopsies between lansoprazole and placebo groups, measured in lymphocytes per square millimeter. Overall mean differences were compared (post-intervention mean lymphocyte count minus pre-intervention mean lymphocyte count) between the two intervention groups.

Secondary Outcome Measures

Log Change in Tumor Necrosis Factor (TNF) Alpha Measurement
Change in TNF alpha cytokine expression from bronchoalveolar lavage aspirate samples between lansoprazole and placebo groups, measured in log picograms per milliliter (log (pg/mL)) units, pre- and post-intervention.

Full Information

First Posted
August 8, 2006
Last Updated
June 25, 2016
Sponsor
University of Utah
search

1. Study Identification

Unique Protocol Identification Number
NCT00361972
Brief Title
Elucidation of Acid-Induced Pulmonary Inflammation
Official Title
Elucidation of Acid-Induced Pulmonary Inflammation
Study Type
Interventional

2. Study Status

Record Verification Date
June 2016
Overall Recruitment Status
Terminated
Why Stopped
limited recruitment
Study Start Date
August 2006 (undefined)
Primary Completion Date
April 2009 (Actual)
Study Completion Date
April 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Utah

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study will evaluate how heartburn may lead to different types of inflammation in one's airways. Additionally, the study will determine whether aggressive treatment of heartburn results in improvement in both symptoms of heartburn and asthma but also in documented improvement in airway inflammation as determined by biopsy. The results of this study will be important in directing future research into the relationship between heartburn and asthma and may provide a clue whether certain subtypes of asthma may be caused primarily by gastroesophageal reflux (GER).
Detailed Description
Currently, many Americans suffer from asthma. The exact mechanism by which airway inflammation leads to asthma symptoms has yet to be clearly explained. In previous studies, persons with asthma appear to have different types of inflammation in their lungs. The reasons for this difference remain a mystery. Allergy is known to play a role in bronchospasm. Other mechanisms have not been discovered. It is known that asthma and heartburn are correlated. Studies have confirmed a direct relationship between cough and heartburn (Gastroesophageal reflux). Other researchers have determined that asthma is often worsened by GER. Determination of the exact relationship between these two entities remains unclear. Heartburn may contribute to airway inflammation in asthmatics, resulting in different patterns of inflammation between those people with and without GER. In fact, adult-onset asthma may result primarily from longstanding heartburn. This has yet to be proven. This study will evaluate how heartburn may lead to different types of inflammation in one's airways. Additionally, the goal of this study is to determine whether aggressive treatment of heartburn results in improvement in both symptoms of heartburn and asthma but also in documented improvement in airway inflammation as determined by biopsy. The results of this study will be important in directing future research into the relationship between heartburn and asthma and may provide a clue whether certain subtypes of asthma may be caused primarily by GER. A total of 30 subjects will be studied, randomized to twice daily lansoprazole or placebo. Study procedures are as follows: A. Esophageal studies and validated questionnaires: Patients will be evaluated with validated SF-36 Quality of Life Questionnaire, Mini-asthma Quality of Life Questionnaire, and GER Questionnaire. Patients will undergo esophageal manometry and pH detection with a 24- hour pH probe to confirm the presence of pathologic GER. B. Bronchoscopy: After an overnight fast, subjects will report to the bronchoscopy suite as directed. Bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsy will be performed following the University of Utah's standardized protocol. Bronchoscopy and endobronchial biopsies present minimal risk to asthmatic airways when performed by appropriate, trained personnel. Conscious sedation with intravenous remifentanyl and propofol will be administered by a trained nurse experienced in conscious sedation. The nose and pharynx will be anesthetized with 1% lidocaine administered by nebulization and by lidocaine jelly administered topically to the nasal mucosa. Additional lidocaine will be administered via the bronchoscope to the vocal cords, trachea, main carina and mainstem bronchi. The total dose of lidocaine will not exceed 400 mg. All subjects will have continuous cardiac and oxygen saturation monitoring and will receive supplemental oxygen during the procedure sufficient to maintain SpO2 > 90%. The subject will be placed in a recumbent position and the bronchoscope will be introduced via the nose. After passing the vocal cords, the bronchoscope will be introduced via the right mainstem bronchus into the right middle lobe where it will be wedged into a segmental bronchus. (Should, for any reason, the right middle lobe be inaccessible, the same procedure will be used to wedge the bronchoscope into a lingular segment in the left lung.) A 60 cc aliquot of room temperature normal saline will be instilled through the bronchoscope and recovered using the same syringe. This procedure will be repeated three more times (total lavage volume of 240 cc) and the recovered volumes will be pooled and measured. Forceps biopsies of respiratory mucosa will then be taken from the trachea, main carina, bronchus intermedius and right middle lobe areas. Two to six biopsies will be taken from each site. Specific tissue from each site will be frozen and stored for future use. Individuals will be randomized to lansoprazole 30 mg twice daily or placebo (all patients will undergo lifestyle modification for reflux) for 6 weeks. It has been determined in previous studies that higher levels of acid suppression are needed to result in clinical improvement in asthma. Patients will be monitored by telephone at regular intervals. Rescue inhaler use, hospitalizations, exercise tolerance, and study compliance will be assessed and recorded to document clinical progress. Patients will be asked to maintain their standard inhaler therapy (especially that of inhaled steroids). Any changes to the therapy will be immediately reported to the investigators. If subjects experience an acute flare, appropriate medications will be given until the patient is stable to return to their initial inhaler regimen. If patients remain on stable medication throughout the trial, repeat bronchoscopy will be performed at 6 weeks. After 6 weeks, patients will once again undergo bronchoscopy with BAL/biopsies. Cytokine protein arrays will be repeated. Comparisons will then be made intra-group before and after therapy. Additional comparisons of inflammation and bronchial hyper-responsiveness will be made between groups. Randomization will allow the investigators to control for any changes in cytokine patterns due to seasonal affect (if both groups reduce the concentration of Interleukin-5 in a similar pattern, this is more likely seasonal than due to acid suppression). Primary outcome will include change in cellular infiltration in the bronch specimens of lymphocytes. Secondary outcome will include RNA expression changes of tumor necrosis factor (TNF) alpha from BAL samples.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastroesophageal Reflux, Asthma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lansoprazole therapy
Arm Type
Active Comparator
Arm Description
Lansoprazole 30 mg orally twice daily
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
placebo orally twice daily
Intervention Type
Drug
Intervention Name(s)
lansoprazole
Other Intervention Name(s)
Prevacid
Intervention Description
30 mg of lansoprazole twice daily for 6 weeks
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
placebo comparator to lansoprazole 30 mg, twice daily for 6 weeks
Primary Outcome Measure Information:
Title
Change in Lymphocyte Count
Description
Change in mean lymphocyte count in bronchus intermedius biopsies between lansoprazole and placebo groups, measured in lymphocytes per square millimeter. Overall mean differences were compared (post-intervention mean lymphocyte count minus pre-intervention mean lymphocyte count) between the two intervention groups.
Time Frame
Baseline and 6 weeks
Secondary Outcome Measure Information:
Title
Log Change in Tumor Necrosis Factor (TNF) Alpha Measurement
Description
Change in TNF alpha cytokine expression from bronchoalveolar lavage aspirate samples between lansoprazole and placebo groups, measured in log picograms per milliliter (log (pg/mL)) units, pre- and post-intervention.
Time Frame
Baseline and 6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: chronic cough consistent with bronchoreactivity Gastroesophageal reflux Exclusion Criteria: Severe asthmatics who have been hospitalized within the last 6 months or who have required oral steroid use within the last 4 weeks Severe coronary artery disease Cigarette/cigar smoking within the last 6 months Documented allergies affecting the respiratory system Subjects with contraindications to pH/impedance probe Hemophilia Septal deviation Subjects with contraindications to bronchoscopy as outlined by the American Thoracic Society Guidelines Anticoagulation Pregnancy Incarcerated patients Current oral steroid use (may suppress levels of inflammation) Upper respiratory infection within the last 2 weeks Ongoing acid suppression with a proton pump inhibitor, however, patients may be included if they have discontinued their proton pump inhibitor within the last 1 month with stable asthma symptoms as defined by stable utilization of inhaled steroids
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kathryn Peterson, MD
Organizational Affiliation
University of Utah
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Utah Health Sciences Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Elucidation of Acid-Induced Pulmonary Inflammation

We'll reach out to this number within 24 hrs