Glycine Buffer for Airway pH Measurement in Asthma
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
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
Trial Summary
What is the purpose of this trial?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.
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.
What data supports the effectiveness of the treatment Glycine Buffer for airway pH measurement in asthma?
Research suggests that inhaling an alkaline glycine buffer can safely increase the pH in the airways without harming lung function, which may help manage conditions like asthma where airway acidification is a concern.
12345Is Glycine Buffer safe for human use?
The research articles provided do not contain specific safety data for Glycine Buffer or its variants in humans.
678910How is the Glycine Buffer treatment different from other asthma treatments?
The Glycine Buffer treatment is unique because it involves inhaling a solution that helps to balance the pH levels in the airways, potentially reducing acidity without affecting lung function. This approach is different from typical asthma treatments that focus on reducing inflammation or opening airways.
134511Eligibility Criteria
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.
+22 more
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.
+36 more
Trial Timeline
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
Participant Groups
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.
3Treatment groups
Experimental Treatment
Group I: Healthy ControlExperimental Treatment1 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 FibrosisExperimental Treatment1 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: AsthmaExperimental Treatment1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University Hospitals Cleveland Medical Center - Asthma Research CenterCleveland, OH
Indiana University School of MedicineIndianapolis, IN
Loading ...
Who Is Running the Clinical Trial?
Case Western Reserve UniversityLead Sponsor
National Institutes of Health (NIH)Collaborator
National Heart, Lung, and Blood Institute (NHLBI)Collaborator
University Hospitals Cleveland Medical CenterCollaborator
References
Safety of an alkalinizing buffer designed for inhaled medications in humans. [2021]Airway acidification plays a role in disorders of the pulmonary tract. We hypothesized that the inhalation of alkalinized glycine buffer would measurably alkalinize the airways without compromising lung function or causing adverse events. We evaluated the safety of an inhaled alkaline glycine buffer in both healthy subjects and in subjects with stable obstructive airway disease.
[METHODOLOGICAL FEATURES OF THE pH-METRY IN PATIENTS WITH A COMBINATION OF GASTROESOPHAGEAL REFLUX DISEASE AND BRONCHIAL ASTHMA]. [2018]Conducting daily pH monitoring in patients with asthma has a number of features. Due to the fact that the introduction of the pH probe in such patients may provoke an asthma attack, necessary pre-treatment of the patients to the study. It is necessary to perform the procedure for achieving remission of asthma medication. Utility of the modified pH measuring techniques (prolonged, 48-hour) is the need to identify pathological gastroesophageal reflux in patients with asthma and evaluate the effectiveness of antisecretory drugs, allowing for improved asthma, increasing the period of remission, and to improve the quality of life of patients.
Acid-base equilibrium in exhaled breath condensate of allergic asthmatic children. [2013]The dysregulation of airway pH control may have a role in asthma pathophysiology. The measurement of exhaled breath condensate (EBC) pH and ammonia levels may be used as a noninvasive method to study acid-base status in the airway of asthmatics.
Utility of 24-hour pharyngeal pH monitoring and clinical feature in laryngopharyngeal reflux disease. [2019]Label="BACKGROUND" NlmCategory="BACKGROUND">pH monitoring can reflect the changes in H+ in the airway.
An evaluation of the acidogenic potential of asthma inhalers. [2022]The aims of the present study were firstly to investigate the inherent pH and titratable acidity of commercially available paediatric asthma inhalers in the United Kingdom and secondly to assess their in vivo acidogenic potential (saliva pH and plaque pH (PpH) tests) in a group of healthy adult volunteers.
Glycine crystallization during spray drying: the pH effect on salt and polymorphic forms. [2013]Spray drying of aqueous solutions of glycine revealed a strong pH effect on the salt and polymorphic forms of the resulting powders. Adjusting pH by aqueous HCl or NaOH between 1.7 and 10.0 caused the glycine solutions to crystallize as two polymorphs (alpha and gamma) of the neutral glycine ((+)H(3)NCH(2)CO(2) (-)) and as three salts (diglycine HCl, (+)H(3)NCH(2)CO(2) (-). (+)H(3)NCH(2)CO(2)H. C1(-); glycine HCl, (+)H(3)NCH(2)CO(2)H. C1(-); and sodium glycinate, H(2)NCH(2)CO(2) (-). Na(+)). Although alpha-glycine crystallized from solutions without pH adjustment (pH 6.2), changing the pH to 4.0 and 8.0 caused gamma-glycine to crystallize as the preferred polymorph. This phenomenon is attributed to the pH effect on the dimeric growth unit of alpha-glycine. The formation of alpha-glycine by spray drying solutions of neutral glycine contrasts the outcome of freeze drying, which yields beta-glycine. Because gamma-glycine is thermodynamically more stable than alpha-glycine, the crystallization of gamma-glycine by pH adjustment provides a way to improve the physical stability of glycine-containing formulations. Spray drying at low pH yielded various mixtures of neutral glycine and its HCl salts: pH 3.0, gamma-glycine and diglycine HCl; pH 2.0, diglycine HCl; and pH 1.7 (the natural pH of glycine HCl), diglycine HCl (major component) and glycine HCl (minor component). Spray drying glycine HCl solutions (pH 1.7) yielded the same diglycine HCl/glycine HCl mixture as did spray drying neutral glycine solutions acidified to pH 1.7. Obtaining diglycine HCl by spray drying glycine HCl solutions indicates a 50% loss of HCl during processing. The extent of HCl loss could be altered by changing the inlet temperature of the spray drier. Spray drying glycine solutions at pH 9.0 and 10.0 gave predominantly gamma-glycine and an additional crystalline product, possibly sodium glycinate. The glycine powders spray dried at different pH had different particle morphologies and sizes, which may influence their suitability for pharmaceutical formulations.
Effect of glycine on pH changes and protein stability during freeze-thawing in phosphate buffer systems. [2013]Previous studies have established that the selective precipitation of a less soluble buffer component during freezing can induce a significant pH shift in the freeze concentrate. During freezing of sodium phosphate solutions, crystallization of the disodium salt can produce a pH decrease as great as 3 pH units which can dramatically affect protein stability. The objective of our study was to determine how the presence of glycine (0-500 mM), a commonly used bulking agent in pharmaceutical protein formulations, affects the pH changes normally observed during freezing in sodium phosphate buffer solutions and to determine whether these pH changes contribute to instability of model proteins in glycine/phosphate formulations. During freezing in sodium phosphate buffers, the presence of glycine significantly influenced the pH. Glycine at the lower concentrations ( 100 mM) in the sodium phosphate buffer resulted in a more complete crystallization of the disodium salt as indicated by the frozen pH values closer to the equilibrium value (pH 3.6). Although high concentrations of glycine can facilitate more buffer salt crystallization and these pH shifts may prove to be potentially damaging to the protein, glycine, in its amorphous state, can also act to stabilize a protein via the preferential exclusion mechanism.
Traceability of pH measurements by glass electrode cells: performance characteristic of pH electrodes by multi-point calibration. [2016]Routine pH measurements are carried out with pH meter-glass electrode assemblies. In most cases the glass and reference electrodes are thereby fashioned into a single probe, the so-called 'combination electrode' or simply 'the pH electrode'. The use of these electrodes is subject to various effects, described below, producing uncertainties of unknown magnitude. Therefore, the measurement of pH of a sample requires a suitable calibration by certified standard buffer solutions (CRMs) traceable to primary pH standards. The procedures in use are based on calibrations at one point, at two points bracketing the sample pH and at a series of points, the so-called multi-point calibration. The multi-point calibration (MPC) is recommended if minimum uncertainty and maximum consistency are required over a wide range of unknown pH values. Details of uncertainty computations for the two-point and MPC procedure are given. Furthermore, the multi-point calibration is a useful tool to characterise the performance of pH electrodes. This is demonstrated with different commercial pH electrodes. ELECTRONIC SUPPLEMENTARY MATERIAL is available if you access this article at http://dx.doi.org/10.1007/s00216-002-1506-5. On that page (frame on the left side), a link takes you directly to the supplementary material.
A dynamic system for the simulation of fasting luminal pH-gradients using hydrogen carbonate buffers for dissolution testing of ionisable compounds. [2013]The hydrogen carbonate buffer is considered as the most biorelevant buffer system for the simulation of intestinal conditions and covers the physiological pH range of the luminal fluids from pH 5.5 to about pH 8.4. The pH value of a hydrogen carbonate buffer is the result of a complex and dynamic interplay of the concentration of hydrogen carbonate ions, carbonic acid, the concentration of dissolved and solvated carbon dioxide and its partial pressure above the solution. The complex equilibrium between the different ions results in a thermodynamic instability of hydrogen carbonate solutions. In order to use hydrogen carbonate buffers with pH gradients in the physiological range and with the dynamics observed in vivo without changing the ionic strength of the solution, we developed a device (pHysio-grad®) that provides both acidification of the dissolution medium by microcomputer controlled carbon dioxide influx and alkalisation by degassing. This enables a continuous pH control and adjustment during dissolution of ionisable compounds. The results of the pH adjustment indicate that the system can compensate even rapid pH changes after addition of a basic or acidic moiety in amounts corresponding up to 90% of the overall buffer capacity. The results of the dissolution tests performed for a model formulation containing ionizable compounds (Nexium 20mg mups) indicate that both the simulated fasting intraluminal pH-profiles and the buffer species can significantly affect the dissolution process by changing the lag time prior to initial drug release and the release rate of the model compound. A prediction of the in vivo release behaviour of this formulation is thus most likely strongly related to the test conditions such as pH and buffer species.
Buffers for the physiological pH range: acidic dissociation constants of zwitterionic compounds in various hydroorganic media. [2019]The measurement of pH of a physiological buffer is an integral part of clinical diagnosis. For the standardization of pH and control of acidity in the physiological region of pH 7 to 9, as found in blood and plasma. Good et al., Ferguson et al., and Bellini et al. have listed hydrogen buffers which are N-substituted amino acids compatible with common biological media. Recently, the acid base behavior of BICINE, in aqueous solution and in different solvent mixtures has been studied by us. Other investigators reported similar results for (CAPS and CAPSO), (BES), (ACES and CHES), TRICINE, TES, ADA, (HEPPS and MOPSO), (MOPS), and (MOBS and HEPBS). These studies have provided precise knowledge about the suitability of a biological buffer. No work seems to have been done on the determination of second stage dissociation constants of 2-(4-Morphlinomethyl)propenoic acid, 2-[bis(2-hydroxyethyl)amino methyl]propenoic acid, 2-[bis(2-hydroxypropyl)aminomethyl]propenoic acid, and 2-[N-ethyl-N-(2-hydroxyethyl)aminomethyl]propenoic acid in aquo-organic solvent mixtures.
The role of titratable acidity in acid aerosol-induced bronchoconstriction. [2019]We evaluated the importance of pH, titratable acidity, and specific chemical composition in acid aerosol-induced bronchoconstriction in 8 asthmatic subjects. We administered aerosols of HCl and H2SO4 at pH 2.0 in an unbuffered state and buffered with glycine. The buffered acids were given in order of increasing titratable acidity (defined as the number of ml of 1 N NaOH required to neutralize 100 ml of acid solution to pH 7.0). Each set of buffered or unbuffered acid aerosols was given on a separate day and each aerosol was inhaled through a mouthpiece during 3 min of tidal breathing. Bronchoconstriction was assessed by measurement of specific airway resistance (SRaw) before and after inhalation of each aerosol. SRaw increased by more than 50% above baseline in 1 of 8 subjects after inhalation of unbuffered HCl and in no subjects after inhalation of unbuffered H2SO4, even at pH 2.0. In contrast, SRaw increased by greater than 50% in all 8 subjects after inhalation of HCl and glycine at pH 2.0 and 7 of 8 subjects after inhalation of H2SO4 and glycine at pH 2.0. The mean titratable acidity required to increase SRaw by 50% above baseline was calculated for each challenge by linear interpolation; these values for H2SO4 and glycine (5.1 ml of 1 N NaOH) and HCl and glycine (2.2 ml of 1 N NaOH) were slightly, but significantly, different (p = 0.01) and were considerably higher than the titratable acidity of the unbuffered acids at pH 2 (1.0 ml of 1 N NaOH).(ABSTRACT TRUNCATED AT 250 WORDS)