Project 2 Airway Potential Hydrogen (pH) in Asthma

NCT03617718 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 03-18-28P01HL158507
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 2

Brief Summary

This study is testing a non invasive way to measure airway pH in individuals with Asthma and Cystic Fibrosis using a new inhaled drug. The airway pH will help health care providers in creating tailored treatment plans for individuals suffering from these specific conditions.

Conditions

Cystic Fibrosis; Asthma; Severe Persistent Asthma; Healthy

Outcome Measures

Primary Outcomes (5)

• Changes in Fractional Exhaled Nitric Oxide (FeNO) levels

  FeNO measurements will be compared among the three different participant groups (Cystic Fibrosis, Severa Asthma and Healthy Volunteers).

  Baseline, every 15 minutes after administration of glycine buffer for 60 minutes

• Frequency of shared phenotypic features among participants with low airway pH compared to those with low exhaled breath condensate (EBC) pH

  The number of times that the phenotypic features of low EBC pH ( high BMI (\>30), low methacholine PC20 (\<5), age, and bronchoalveolar lavage neutrophils) are also shared with participants that are found to have a low airway pH.

  Baseline, 3 months

• Large airway pH as measured by bronchoscopy

  Visit 3 (day 21)

• Middle airway pH as measured by bronchoscopy

  Visit 3 (day 21)

• Lower airway pH as measured by bronchoscopy

  Visit 3 (day 21)

Study Arms (3)

Cystic Fibrosis

EXPERIMENTAL

All Cystic Fibrosis participants will undergo screening, baseline characterization, a non-invasive challenge test with inhaled alkaline glycine buffer, followed by repeated measurements of airway function and inflammation, and a research bronchoscopy.

Drug: Glycine Buffer

Asthma

EXPERIMENTAL

All Asthma participants will undergo screening, baseline characterization, a non-invasive challenge test with inhaled alkaline glycine buffer, followed by repeated measurements of airway function and inflammation, and a research bronchoscopy.

Drug: Glycine Buffer

Healthy Control

EXPERIMENTAL

All Healthy Control participants will undergo screening, baseline characterization, a non-invasive challenge test with inhaled alkaline glycine buffer, followed by repeated measurements of airway function and inflammation, and a research bronchoscopy.

Drug: Glycine Buffer

Interventions

Glycine Buffer DRUG

Subjects will be asked to perform an Inhaled Glycine Buffer followed by a series of Pulmonary Function Tests (PFTs) and then a research bronchoscopy will happen at visit 3.

Asthma; Cystic Fibrosis; Healthy Control

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects with Severe Asthma
• Asthma diagnosis established during at least 3 months of evaluation and care by an asthma specialist (pulmonologist or allergist).
• Adult male or female age ≥ 18 and ≤ 50 years at the time of enrollment
• Forced expiratory volume in 1 second (FEV1) bronchodilator reversibility \> 12% or methacholine FEV1 by 20% of baseline (PC20) \< 16 mg/ml (historical methacholine data from previous NIH trial including Severe Asthma Research Program (SARP) or Asthma Network (AsthmaNet) will be allowed).
• If FEV1 is \<50% predicted, precluding methacholine challenge testing, investigator acceptance of the diagnosis of asthma is acceptable
• Treatment with high-dose inhaled corticosteroids (\> 880 mcg fluticasone or highest marketed equivalent/day) along with a second controller or systemic corticosteroids for at least 3 months prior to enrollment and for at least 6 of the last 12 months.
• Lack of asthma control despite this treatment evidenced by any one of the following:
• Asthma Control Questionnaire (ACQ) \> 1.5 or Asthma Control Test (ACT) \< 20
• \>2 bursts of systemic corticosteroids (3 days or more) in the previous 12 months
• \>1 hospitalization or ICU stay for acute asthma in the previous 12 months
• Mild to moderate obstructive lung disease with 45%\< FEV1 \< 80% predicted (with low FEV1/FVC) prior to bronchodilator
• Healthy Volunteers
• Adult males or females age ≥ 18 and ≤ 50 years at time of enrollment
• Non-smokers
• No history of asthma, chronic obstructive pulmonary disease (COPD), or other chronic lung disease

You may not qualify if:

• General (applying to all participants)
• \> 5 pack year smoking history
• Body mass index (BMI) greater than 45
• Unable to perform repeatable consistent efforts in pulmonary function testing
• Individuals with prior diagnosis of vocal cord dysfunction or an anatomic anomaly that would increase the risks associated with the bronchoscopy procedure
• Prior diagnosis of any chronic lung disease that in the investigator's opinion would make them unsuitable for study participation
• History of premature birth before 35 weeks gestation
• Planning to relocate away from the clinical center (Cleveland, Ohio) area before study completion
• Lack of reliable communications channel (hard-wire phone, cell phone, email for follow-up contacts after bronchoscopy)
• Allergic to anesthetic medication(s) that would prevent participation in the study's bronchoscopy
• Blood pressure parameters outside the normal range of 90-180 mm Hg systolic and 50-100 mm Hg diastolic at time of screening
• Individuals with diabetes mellitus (type 1 or type 2) (subjects with CF who have CF related diabetes may be enrolled)
• Individuals with renal failure or creatinine \> 1.8 mg/dl at time of screening
• Individuals who are pregnant, breastfeeding, or are unwilling to use a medically acceptable method of birth control (as indicated on the Birth Control Methods Reference Card) from the time of consent until the end of the study to avoid pregnancy
• Individuals who report additional chronic diseases requiring medication of the heart, lungs, kidney, liver, brain, etc., or afflicted with any acute or chronic pathology that in the opinion of the screening physician makes them unsuitable for study such as coronary artery disease

Sponsors & Collaborators

• Case Western Reserve University: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• University Hospitals Cleveland Medical Center: collaborator

Study Sites (2)

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

University Hospitals Cleveland Medical Center - Asthma Research Center

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Cystic Fibrosis; Asthma

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Kristie R Ross, MD

  University Hospitals Cleveland Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: All participants will go through the same study procedures.

Study Record Dates

• First Submitted: July 19, 2018
• First Posted: August 6, 2018
• Study Start: November 1, 2018
• Primary Completion: July 16, 2025
• Study Completion: July 16, 2025
• Last Updated: August 15, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, CSR
• Time Frame: Available Immediately following publication. No end date
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.

Locations

US (2)