Glycine Buffer for Airway pH Measurement in Asthma

No longer recruiting at 1 trial location

Overseen By Rebecca Gammell

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Case Western Reserve University

Must be taking: Inhaled corticosteroids

Must not be taking: Anticoagulants, Beta-blockers

Disqualifiers: Diabetes, Renal failure, Chronic lung disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new inhaled drug, glycine buffer, to measure airway pH levels in people with asthma and cystic fibrosis. The goal is to find a non-invasive method to gather information that helps doctors create tailored treatment plans for these conditions. Participants will undergo tests to assess airway function and inflammation. Those with severe, hard-to-control asthma or cystic fibrosis in stable health might be suitable for the trial. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude participants using certain medications like vitamin K antagonists, beta-adrenergic blockers, and tricyclic antidepressants. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that the Glycine Buffer is likely to be safe for humans?

Research has shown that inhaling an alkaline glycine buffer is generally safe. Studies found no negative effects on participants' lung function or vital signs, indicating that the treatment did not harm their breathing or overall health during the studies. However, ongoing research is necessary to confirm these findings, as with any new treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the trial of inhaled alkaline glycine buffer for asthma because it offers a novel way to measure airway pH, which could provide new insights into the condition. Unlike traditional treatments that focus on reducing inflammation or dilating airways, this approach aims to understand the role of airway acidity in asthma. By improving our understanding of airway pH, this trial could lead to more targeted and effective treatments in the future.

What evidence suggests that this inhaled glycine buffer is effective for measuring airway pH in asthma and cystic fibrosis?

Research has shown that inhaling a special alkaline solution, such as the Glycine Buffer used in this trial, can safely raise the pH level in the airways. In earlier studies, this treatment did not harm lung function or overall health. The solution reduces acidity in the airways, potentially benefiting people with asthma and cystic fibrosis. This pH change might aid in developing better treatments for these conditions. Overall, using this solution has shown promise in safely adjusting airway pH without negative effects. Participants in this trial will undergo a non-invasive challenge test with inhaled alkaline glycine buffer to further evaluate its effects. ^{1 3 6 7 8}

Who Is on the Research Team?

Kristie Ross, MD

Principal Investigator

University Hospitals Cleveland Medical Center

Are You a Good Fit for This Trial?

Adults aged 18-50 with Asthma or Cystic Fibrosis can join this trial. For asthma, they need a history of severe symptoms and poor control despite treatment. People with cystic fibrosis must have mild lung disease and meet diagnostic criteria. Healthy volunteers without chronic lung diseases or severe allergies are also eligible. Exclusions include certain medications, recent exacerbations, other chronic illnesses, pregnancy, smoking history over 5 pack years, and inability to perform consistent pulmonary tests.

Inclusion Criteria

My health has been stable, and my lung function hasn't significantly changed in the last 4 weeks.

People who are not experiencing any health issues.

I have severe asthma.

Exclusion Criteria

I haven't had an asthma attack in the last 4 weeks.

Your blood pressure is too high or too low at the time of screening.

I haven't started any new long-term treatments in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Characterization

Participants undergo baseline characterization including non-invasive challenge test with inhaled alkaline glycine buffer

1 week

1 visit (in-person)

Non-invasive Challenge Test

Participants receive the Glycine Buffer inhalation and undergo repeated measurements of airway function and inflammation

1 day

1 visit (in-person)

Research Bronchoscopy

Participants undergo a bronchoscopy to measure airway pH and other parameters

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the challenge test and bronchoscopy

3 months

Periodic follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Glycine Buffer

Trial Overview The trial is testing an inhaled Glycine Buffer to measure airway pH non-invasively in individuals with Asthma and Cystic Fibrosis. The goal is to help healthcare providers create personalized treatment plans based on the airway pH levels measured during the study procedures.

How Is the Trial Designed?

Group I: Healthy Control Experimental Treatment 1 Intervention

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.

Group II: Cystic Fibrosis Experimental Treatment 1 Intervention

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.

Group III: Asthma Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Case Western Reserve University

Lead Sponsor

Trials

314

Recruited

236,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

University Hospitals Cleveland Medical Center

Collaborator

Trials

348

Recruited

394,000+

Published Research Related to This Trial

In a study of 956 patients suspected of having laryngopharyngeal reflux disease (LPRD), the Ryan score, which is considered a gold standard for diagnosis, showed poor correlation with other assessment tools like the Reflux Symptom Index (RSI) and Reflux Finding Score (RFS), indicating that some cases of LPRD may be missed.

Pharyngeal pH monitoring is suggested as a useful diagnostic tool for LPRD, highlighting the need for more effective indices to improve detection rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of 24-hour pharyngeal pH monitoring and clinical feature in laryngopharyngeal reflux disease. Wang, G., Qu, C., Wang, L., et al.[2019]

Daily pH monitoring in asthma patients can help identify gastroesophageal reflux, which may contribute to asthma symptoms, but requires careful pre-treatment to avoid triggering asthma attacks.

Using modified pH measuring techniques over 48 hours can assess the effectiveness of antisecretory medications, potentially leading to better asthma management and improved quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[METHODOLOGICAL FEATURES OF THE pH-METRY IN PATIENTS WITH A COMBINATION OF GASTROESOPHAGEAL REFLUX DISEASE AND BRONCHIAL ASTHMA]. Kazyulin, AN., Dicheva, DT., Parcvania-Vinogradova, EV., et al.[2018]

Inhalation of an alkaline glycine buffer safely alkalinizes the airways without causing any adverse effects on lung function or vital signs, as shown in a study involving 20 non-smoking adults (10 healthy and 10 with obstructive airway disease).

The study demonstrated a significant increase in the pH of exhaled breath condensate (EBC) by 0.235 pH units after inhalation of the higher-dose alkaline buffer, confirming effective airway alkalinization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of an alkalinizing buffer designed for inhaled medications in humans. Davis, MD., Walsh, BK., Dwyer, ST., et al.[2021]

The study found that adding glycine to sodium phosphate buffer solutions during freezing can significantly influence pH changes, with lower concentrations (≤ 50 mM) helping to suppress the pH decrease that typically occurs, which is important for maintaining protein stability.

At higher concentrations (> 100 mM), glycine can lead to more complete crystallization of the buffer salt, potentially causing harmful pH shifts, but it can also stabilize proteins through a mechanism that prevents them from interacting with the crystallizing salts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of glycine on pH changes and protein stability during freeze-thawing in phosphate buffer systems. Pikal-Cleland, KA., Cleland, JL., Anchordoquy, TJ., et al.[2013]

In a study involving 8 asthmatic subjects, inhalation of buffered HCl and H2SO4 at pH 2.0 caused significant bronchoconstriction, with all subjects showing increased airway resistance after HCl and glycine, and 7 out of 8 after H2SO4 and glycine.

The results indicate that the buffering of acids with glycine increases their titratable acidity, which is linked to a greater bronchoconstrictive response, suggesting that both pH and chemical composition play critical roles in airway reactivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of titratable acidity in acid aerosol-induced bronchoconstriction. Fine, JM., Gordon, T., Thompson, JE., et al.[2019]

The study found that dry powder inhalers (DPIs) have a significantly lower inherent pH (mean pH 5.06) compared to metered dose inhalers (MDIs) (mean pH 6.45), indicating that DPIs may be more acidic.

Lactose-based DPIs resulted in greater drops in salivary and plaque pH, which could pose a risk for enamel demineralization, although none of the inhalers tested caused plaque pH to drop below the critical level of pH 6.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of the acidogenic potential of asthma inhalers. Tootla, R., Toumba, KJ., Duggal, MS.[2022]

In a study of 29 allergic stable asthmatic children and 13 healthy controls, exhaled breath condensate (EBC) pH levels were significantly lower in asthmatics, suggesting airway acidification may contribute to asthma pathophysiology.

Ammonia levels in EBC were also lower in asthmatic children compared to controls, and there was a positive correlation between EBC pH and ammonia concentrations, indicating a potential link between these factors in allergic asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acid-base equilibrium in exhaled breath condensate of allergic asthmatic children. Carraro, S., Folesani, G., Corradi, M., et al.[2013]

The study emphasizes the importance of measuring pH in physiological buffers for clinical diagnosis, particularly in the pH range of 7 to 9, which is critical for blood and plasma function.

It highlights the need for further research on the second stage dissociation constants of specific amino acid-based buffers in aquo-organic solvent mixtures, as previous studies have focused on other established buffers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buffers for the physiological pH range: acidic dissociation constants of zwitterionic compounds in various hydroorganic media. Taha, M.[2019]

The pH of glycine solutions significantly affects the crystallization of glycine polymorphs and salts during spray drying, with gamma-glycine being favored at pH 4.0 and 8.0, which can enhance the stability of glycine formulations.

Spray drying at low pH (1.7) results in a mixture of diglycine HCl and glycine HCl, indicating a 50% loss of HCl during processing, which can be adjusted by changing the spray drier's inlet temperature, affecting the final product's properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycine crystallization during spray drying: the pH effect on salt and polymorphic forms. Yu, L., Ng, K.[2013]

Routine pH measurements using combination electrodes can introduce uncertainties, making proper calibration essential for accurate results.

Multi-point calibration (MPC) is recommended for minimizing uncertainty and ensuring consistent pH measurements across a wide range of values, as demonstrated with various commercial pH electrodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Traceability of pH measurements by glass electrode cells: performance characteristic of pH electrodes by multi-point calibration. Naumann, R., Alexander-Weber, Ch., Eberhardt, R., et al.[2016]

The hydrogen carbonate buffer is an effective system for simulating intestinal conditions, maintaining a physiological pH range of 5.5 to 8.4, which is crucial for studying drug dissolution.

The newly developed pHysio-grad® device allows for precise control of pH during dissolution tests, demonstrating that pH and buffer species significantly influence the release rates of ionizable drugs, such as Nexium, which can help predict in vivo drug behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A dynamic system for the simulation of fasting luminal pH-gradients using hydrogen carbonate buffers for dissolution testing of ionisable compounds. Garbacz, G., Kołodziej, B., Koziolek, M., et al.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7610037/

Safety of an Alkalinizing Buffer Designed for Inhaled ... In conclusion, we report that the inhalation of isotonic alkaline glycine is safe in humans with or without obstructive airway disease, and that both EBC pH and ...

2. withpower.com withpower.com/trial/phase-2-cystic-fibrosis-10-2018-b562c

Glycine Buffer for Airway pH Measurement in Asthma Inhalation of an alkaline glycine buffer safely alkalinizes the airways without causing any adverse effects on lung function or vital signs, as shown in a study ...

3. cdek.liu.edu cdek.liu.edu/trial/NCT03617718/

Trial | NCT03617718 This study is testing a non invasive way to measure airway pH in individuals with Asthma and Cystic Fibrosis using a new inhaled drug.

4. researchgate.net researchgate.net/figure/Comparison-of-alkaline-glycine-to-normal-saline-inhalation-study-1-Median-percentage_fig2_233964707

Comparison of alkaline glycine to normal saline inhalation ... We hypothesized that the inhalation of alkalinized glycine buffer would measurably alkalinize the airways without compromising lung function or causing adverse ...

5. researchexperts.utmb.edu researchexperts.utmb.edu/en/publications/safety-of-an-alkalinizing-buffer-designed-for-inhaled-medications

Safety of an alkalinizing buffer designed for inhaled ... RESULTS: Alkaline glycine inhalation was tolerated by all subjects in both studies, with no adverse effects on spirometric parameters or vital signs. Airway ...

6. liebertpub.com liebertpub.com/doi/abs/10.4187/respcare.01753

Safety of an Alkalinizing Buffer Designed for Inhaled ... RESULTS: Alkaline glycine inhalation was tolerated by all subjects in both studies, with no adverse effects on spirometric parameters or vital signs. Airway ...

7. researchgate.net researchgate.net/publication/233964707_Safety_of_an_Alkalinizing_Buffer_Designed_for_Inhaled_Medications_in_Humans

(PDF) Safety of an Alkalinizing Buffer Designed for Inhaled ... Results: Alkaline glycine inhalation was tolerated by all subjects in both studies, with no adverse effects on spirometric parameters or vital ...

8. media.cellsignal.com media.cellsignal.com/s3sds/9004-sds-EN-20241015185706.pdf

Safety Data Sheet (SDS) May cause skin, eye, and respiratory tract irritation. B. Health hazards information. Chemical name. LD50 Oral. LD50 Dermal. LC50 Inhalation.