Cystic FibrosisPhase 1/2NCT03617718
Project 2 Airway Potential Hydrogen (pH) in Asthma
A Phase 1/2 study testing Glycine Buffer in people with Cystic Fibrosis and Asthma, run by Case Western Reserve University at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Cystic Fibrosis, Asthma, Severe Persistent Asthma
- What is being tested?
- Glycine Buffer
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Nov 2018to 16 Jul 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Show all 25Show fewer
- 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
- Post bronchodilator FEV1 < 55% predicted on the day of study procedures including the Inhaled glycine buffer challenge test and bronchoscopy. (These events may be rescheduled in the event participants meet all inclusion criteria at the time of screening)
- 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
- No history of severe allergic/atopic disease requiring immunotherapy or immunomodulators
- Subjects with Cystic Fibrosis
- Adult male or female age ≥ 18 and ≤ 50 at time of enrollment
- Confirmed diagnosis of CF as evidenced by 1 or more clinical features consistent with the CF phenotype and 1 or more of the following laboratory criteria:
- Sweat chloride equal to or greater than 60 m/Eq/L by quantitative pilocarpine iontophoresis test (Sweat Test)
- Two well-characterized disease causing mutations in the Cystic fibrosis transmembrane conductance regulator (CFTR) gene.
- Weight > 50 kg at screening visit
- Mild obstructive lung disease defined as post bronchodilator baseline FEV1 > 70% predicted for age, height and gender
- Clinically stable with no significant changes in health status within 4 weeks, including FEV1 within 10% of baseline, at the time of screening (may be rescreened)
Who cannot join
- 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
Show all 39Show fewer
- 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
- Respiratory or other infection requiring systemic antibiotics within the previous 14 days (can be rescreened)
- Current use of a vitamin K antagonist (warfarin) or other anticoagulant (e.g., heparin, clopidogrel, enoxaparin or dalteparin)
- Current use of beta-adrenergic blockers, tricyclic antidepressants, meperidine (or related central nervous system (CNS) agents), or nitrates
- Inherited or acquired blood coagulation disorder, congenital methemoglobinemia, or a familial hemoglobinopathy that impacts oxygen delivery (e.g., sickle cell)
- Any illness, condition or recent surgeries that may increase the risks associated with the study
- Participation in an investigational drug study within the 4 week period prior to screening (Visit 1)
- Severe Asthma specific exclusion criteria
- Asthma exacerbation within 4 weeks prior to screening (Visit 1) (may be rescreened)
- Initiation of new chronic treatment or change in dose of chronic treatment for asthma within 2 months of screening
- Intubation for asthma within the past 12 months
- More than 3 exacerbations within the past 6 months
- Cystic fibrosis specific exclusion criteria
- Positive sputum culture for Burkholderia cepacia complex organism within the previous 12 months
- Active treatment for non-tuberculous mycobacterium
- International Normalized Ratio (INR) > 1.2 at time of screening
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 times the upper limit of normal at screening, history of biliary cirrhosis or portal hypertension
- Treatment with Kalydeco (ivacaftor) within 12 weeks of screening
- History of pulmonary hypertension
- Severe malnutrition
- Pulse oximetry < 92% at screening or chronic use of supplemental oxygen
- Currently listed for lung or other organ transplantation
- Pneumothorax within 2 years
- Hemoptysis other than trace during the past 12 months or history of life threatening hemoptysis ever
- Initiation of any new chronic treatment with 4 weeks of screening (can be rescreened)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University Hospitals Cleveland Medical Center - Asthma Research Center
Cleveland, Ohio, 44106
Indiana University School of Medicine
Indianapolis, Indiana, 46202
About this study
Official title: Methods to Identify and Treat Severe Asthma Patients Project 2: Airway pH Phenotyping
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.
Read the detailed description
Asthma can affect patients in different ways. Some of the differences in how severe asthma is or how well patients respond to asthma medicines are due to differences in the biology of the airways or breathing tubes. The pH of the airway, which is a measure of the balance between acids and bases in our airways, is one example of how differences in biology can affect asthma and other lung diseases. Airway pH can be measured during a procedure called a bronchoscopy, in which a camera is inserted into the airways or breathing tubes. The lower the pH, the more acid is present. People with lower airway pHs, or more acid present in their airways/breathing tubes, tend to have more trouble with their asthma.
The pH value or acid level in the airway plays a role in respiratory function (breathing) and preventing inflammation (swelling) in the respiratory tract (throat, airways, and lungs). Studies have found that in individuals with asthma, Cystic Fibrosis (CF) and other pulmonary disorders, a lower pH value is present in the airway when compared to healthy individuals. Studies have also found that patients with asthma have a lower airway pH during asthma flares, and may affect how well some breathing medicines work. If we can better identify the changes in the airways or breathing pipes in patients with asthma and CF, we may be able to help patients make better choices about the medicines or treatments that are most likely to work best for each patient.
Right now the only way to measure airway pH is with a bronchoscopy procedure. During a bronchoscopy, a scope with a camera is inserted into the breathing tubes, often under sedation in a special procedure area. This research study is being done to test if we can measure how acidic the airway is in a simple and non-invasive test that can be done in a doctor's office.
This non-invasive diagnostic test, called a Glycine Buffer Challenge test, may be able to identify which asthma and CF patients have low airway pH levels. We are also studying the phenotypes (observable traits) in asthma and CF patients with decreased airway pH values. If this research study is successful, in the future (after this research study is done) we may be able to offer better ways to treat patients with low airway pH.
The Glycine Buffer Challenge test includes giving an investigational drug to breathe in (inhale). The investigational drug is the Glycine Buffer. "Investigational" means the drug is not approved by any regulatory agencies including the Food and Drug Administration (FDA), and is still being tested for safety and effectiveness. The research is registered with the FDA, but again the Glycine Buffer treatment in this study administered (during the Glycine Buffer challenge testing) is not an approved treatment or diagnostic test for asthma.
The study will enroll a total of 75 volunteers; 50 volunteers with severe asthma, 15 volunteers with cystic fibrosis, and 10 healthy volunteers.
- Conditions
- Cystic Fibrosis, Asthma, Severe Persistent Asthma, Healthy
- Being tested
- Glycine Buffer
- Medical subject headings
- Cystic Fibrosis, Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Glycine BufferDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Glycine Buffer |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: Baseline, 3 months
Large airway pH as measured by bronchoscopy
Measured: Visit 3 (day 21)
Middle airway pH as measured by bronchoscopy
Measured: Visit 3 (day 21)
Lower airway pH as measured by bronchoscopy
Measured: Visit 3 (day 21)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2018
- Study start1 Nov 2018
- Primary completion16 Jul 2025
- Study completion16 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- All participants will go through the same study procedures.
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Western Reserve University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), University Hospitals Cleveland Medical Center
- Responsible party
- Principal investigator, Kristie Ross, University Hospitals Cleveland Medical Center
- Investigators
- Kristie R Ross, MD, Principal investigator, University Hospitals Cleveland Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03617718
- Sponsor's protocol ID
- 03-18-28
- Other IDs
- P01HL158507
- Status last verified
- Aug 2025
- First submitted
- 19 Jul 2018
- Last updated
- 15 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All of the individual participant data collected during the trial, after deidentification and analysis will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Methods to Identify and Treat Severe Asthma Patients Project 2: Airway pH Phenotyping
- ClinicalTrials.gov ID
- NCT03617718
- Acronym / sponsor ID
- 03-18-28
- Conditions
- Cystic Fibrosis, Asthma, Severe Persistent Asthma, Healthy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Case Western Reserve UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), University Hospitals Cleveland Medical Center
- Study start
- 1 Nov 2018 (actual)
- Primary completion
- 16 Jul 2025 (actual)
- Study completion
- 16 Jul 2025 (actual)
- First posted
- 6 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Asthma can affect patients in different ways. Some of the differences in how severe asthma is or how well patients respond to asthma medicines are due to differences in the biology of the airways or breathing tubes. The pH of the airway, which is a measure of the balance between acids and bases in our airways, is one example of how differences in biology can affect asthma and other lung diseases. Airway pH can be measured during a procedure called a bronchoscopy, in which a camera is inserted into the airways or breathing tubes. The lower the pH, the more acid is present. People with lower airway pHs, or more acid present in their airways/breathing tubes, tend to have more trouble with their asthma.
The pH value or acid level in the airway plays a role in respiratory function (breathing) and preventing inflammation (swelling) in the respiratory tract (throat, airways, and lungs). Studies have found that in individuals with asthma, Cystic Fibrosis (CF) and other pulmonary disorders, a lower pH value is present in the airway when compared to healthy individuals. Studies have also found that patients with asthma have a lower airway pH during asthma flares, and may affect how well some breathing medicines work. If we can better identify the changes in the airways or breathing pipes in patients with asthma and CF, we may be able to help patients make better choices about the medicines or treatments that are most likely to work best for each patient.
Right now the only way to measure airway pH is with a bronchoscopy procedure. During a bronchoscopy, a scope with a camera is inserted into the breathing tubes, often under sedation in a special procedure area. This research study is being done to test if we can measure how acidic the airway is in a simple and non-invasive test that can be done in a doctor's office.
This non-invasive diagnostic test, called a Glycine Buffer Challenge test, may be able to identify which asthma and CF patients have low airway pH levels. We are also studying the phenotypes (observable traits) in asthma and CF patients with decreased airway pH values. If this research study is successful, in the future (after this research study is done) we may be able to offer better ways to treat patients with low airway pH.
The Glycine Buffer Challenge test includes giving an investigational drug to breathe in (inhale). The investigational drug is the Glycine Buffer. "Investigational" means the drug is not approved by any regulatory agencies including the Food and Drug Administration (FDA), and is still being tested for safety and effectiveness. The research is registered with the FDA, but again the Glycine Buffer treatment in this study administered (during the Glycine Buffer challenge testing) is not an approved treatment or diagnostic test for asthma.
The study will enroll a total of 75 volunteers; 50 volunteers with severe asthma, 15 volunteers with cystic fibrosis, and 10 healthy volunteers.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- All participants will go through the same study procedures.
| Arm | Type | Receives |
|---|---|---|
| Cystic Fibrosis | Experimental | Drug: Glycine BufferAll 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. |
| Asthma | Experimental | Drug: Glycine BufferAll 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. |
| Healthy Control | Experimental | Drug: Glycine BufferAll 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (25 listed)
- 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
Key exclusion criteria (39 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Glycine BufferSubjects 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. | Drug | Asthma, Cystic Fibrosis, Healthy Control |
Primary outcome
Changes in Fractional Exhaled Nitric Oxide (FeNO) levels
Time frame: Baseline, every 15 minutes after administration of glycine buffer for 60 minutes
FeNO measurements will be compared among the three different participant groups (Cystic Fibrosis, Severa Asthma and Healthy Volunteers).
Frequency of shared phenotypic features among participants with low airway pH compared to those with low exhaled breath condensate (EBC) pH
Time frame: Baseline, 3 months
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.
Large airway pH as measured by bronchoscopy
Time frame: Visit 3 (day 21)
Middle airway pH as measured by bronchoscopy
Time frame: Visit 3 (day 21)
Lower airway pH as measured by bronchoscopy
Time frame: Visit 3 (day 21)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2025.
- Individual participant dataSharing planned: Yes. All of the individual participant data collected during the trial, after deidentification and analysis will be shared.
Related trials for Cystic Fibrosis
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kristie R Ross, MD principal investigator
University Hospitals Cleveland Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Glycine Buffer in people with Cystic Fibrosis and Asthma, run by Case Western Reserve University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Fractional Exhaled Nitric Oxide (FeNO) levels (time frame: Baseline, every 15 minutes after administration of glycine buffer for 60 minutes). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2025.