Ignite Creation Date:
2024-05-05 @ 12:10 PM
Last Modification Date:
2024-10-26 @ 9:21 AM
Study NCT ID:
NCT00262652
Status:
TERMINATED
Last Update Posted:
2011-06-27
First Post:
2005-12-06
Brief Title:
Safety and Efficacy Study of the Use of Sodium Pyruvate Bronchodilation in Asthmatics
Sponsor:
Emphycorp
Organization:
Emphycorp
Study Overview
Official Title:
Sodium Pyruvate Bronchodilation in Asthmatics
Status:
TERMINATED
Status Verified Date:
2005-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Patients did not respond to therapy
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Sodium pyruvate in sodium chloride solution will be delivered by nebulization to the lungs It is believed that this administration will produce bronchodilation in asthmatics as determined by improvement in FEV1 FEV1 is a measure of lung function and will be determined after administration of sodium pyruvate The study is a blinded so subjects may receive either the sodium pyruvate or a sodium chloride placebo The primary endpoint will be the improvement of FEV1 after 15 minutes in subjects receiving sodium pyruvate compared to the FEV1 of subjects receiving the sodium chloride placebo
Detailed Description:
Sodium Pyruvate an intermediate metabolite has been investigated as a therapeutic agent to reduce reactive oxygen species in the lung Evaluation of FEV1 as a safety parameter and sequela of reactive oxygen species reduction identified inhaled Sodium Pyruvate as a potential bronchodilator
A number of lung diseases are typically characterized by marked inflammation at the site of the lung injury This inflammatory process leads to further destruction of surrounding healthy lung tissue and a continuation and expansion of the sites of inflammation This inflammatory process results in the production of reactive oxygen species including superoxide anions and hydrogen peroxide at the site of inflammation
Nitric oxide is a known bronchodilator as well as a vasodilator It has been used successfully used to treat patients with various pulmonary disorders 1 When endogenous nitric oxide is exposed to oxygen radicals however it is converted to the toxic oxidant nitrogen dioxide and its bronchodilating effect is mitigated Conversely nitrogen dioxide is a known deep lung irritant Its adverse consequences include the following pulmonary inflammation reduced levels of lung antioxidants 2 impairment of respiratory defense mechanisms leading to increased susceptibility to respiratory pathogens 3 and increased incidence and severity of respiratory infections reduced lung function and increased asthma and COPD symptoms
Reactive oxygen species especially superoxide anions are known to compromise lung function by increasing bronchoconstriction As a result of the increasing inflammation and the production of reactive oxygen species and the decrease in nitric oxide that is believed to occur with the interstitial lung diseases healthy tissue is damaged and lung function is compromised
Based on our present understanding of the disease process involved with these lung diseases it appears that an intervention in the inflammatory process that would result in a reduction in reactive oxygen species and a subsequent increase in nitric oxide could be an effective way to intervene in the disease process This intervention would prevent the further spread of inflammation and lung damage caused by the production of reactive oxygen species such as superoxide anions and hydrogen peroxide and increase lung function by increasing bronchodilation
Sodium pyruvate is a reactive oxygen species antagonist that has been shown to neutralize oxygen radicals specifically lowering the overproduction of superoxide anions regulate the production and level of other inflammatory mediators and increase the synthesis of nitric oxide 4 Sodium pyruvate also increases cellular levels of glutathione a major cellular antioxidant which is reduced dramatically in antigen-induced lung disease patients 5
In pilot studies in mild asthmatic subjects it was demonstrated that inhalation of low doses 05 mM of nebulized sodium pyruvate decreased expired hydrogen peroxide by 30 at four hours compared to inhalation of a nebulized saline control These subjects also experienced increased pulmonary function as determined by FEV1 128 and PEF 345 measurements after four hours referenced in Cellular Sciences IND 50089 It is theorized that the reactive oxygen species antagonist properties of sodium pyruvate reduced the production of oxygen radicals including hydrogen peroxide and increased the levels of nitric oxide Together this led to reduced inflammation and lung damage and increased lung function through improved bronchodilation
In summary it is believed that inhalation of sodium pyruvate will reduce the lung damage resulting from the increase in reactive oxygen species associated with the inflammation component of the disease and will enhances the availability of nitric oxide to produce bronchodilation by enhancing its synthesis and protecting it from destruction by reactive oxygen species
Experimental Clinical Protocol Hypothesis Sodium Pyruvate delivered by nebulization to the lungs produces bronchodilation in asthmatics as measured by FEV1
Intent Provide support for further drug development of nebulized Sodium Pyruvate as a therapeutic agent in asthma
Design Randomized double-blind placebo-controlled cross-over study of 52 completed subjects
Treatment 1 05 mM sodium pyruvate in 09 saline solution 5ml Cellular Sciences CA nebulized via a Pari LC PlusR reusable nebulizer powered by a ProNebR compressor Midlothian VA Treatment 2 Saline 09 5ml Baxter nebulized using the same nebulizer system as above A randomization algorithm using random permuted blocks 4-8 subjects will be used to generate treatment order assignments An unblinded statistician will generate this list of treatment order assignments
Patient Recruitment and Selection The large cohort of potential subjects who have previously participated in asthma studies through our clinical research laboratory will be apprised of the study Patients attending the UCLA Asthma and Cough Center will also be informed of the study Advertisements will be sent by regular mail and by e-mail to physicians participating in the UCLA Healthcare System and to local pulmonologists practicing throughout the Los Angeles area Local Allergists who collaborate with us in common clinical trial protocols will be informed of the study by personalized letter and e-mail Advertisements will be placed in the classified andor health sections of local newspapers A description of the study will be posted on internet sites featuring clinical research trials
Subjects will be recruited until a total of 52 complete the study Assuming a 5 drop-out and non-compliance rate we expect a total of 55 subjects recruited Patient Eligibility Criteria
A number of lung diseases are typically characterized by marked inflammation at the site of the lung injury This inflammatory process leads to further destruction of surrounding healthy lung tissue and a continuation and expansion of the sites of inflammation This inflammatory process results in the production of reactive oxygen species including superoxide anions and hydrogen peroxide at the site of inflammation
Nitric oxide is a known bronchodilator as well as a vasodilator It has been used successfully used to treat patients with various pulmonary disorders 1 When endogenous nitric oxide is exposed to oxygen radicals however it is converted to the toxic oxidant nitrogen dioxide and its bronchodilating effect is mitigated Conversely nitrogen dioxide is a known deep lung irritant Its adverse consequences include the following pulmonary inflammation reduced levels of lung antioxidants 2 impairment of respiratory defense mechanisms leading to increased susceptibility to respiratory pathogens 3 and increased incidence and severity of respiratory infections reduced lung function and increased asthma and COPD symptoms
Reactive oxygen species especially superoxide anions are known to compromise lung function by increasing bronchoconstriction As a result of the increasing inflammation and the production of reactive oxygen species and the decrease in nitric oxide that is believed to occur with the interstitial lung diseases healthy tissue is damaged and lung function is compromised
Based on our present understanding of the disease process involved with these lung diseases it appears that an intervention in the inflammatory process that would result in a reduction in reactive oxygen species and a subsequent increase in nitric oxide could be an effective way to intervene in the disease process This intervention would prevent the further spread of inflammation and lung damage caused by the production of reactive oxygen species such as superoxide anions and hydrogen peroxide and increase lung function by increasing bronchodilation
Sodium pyruvate is a reactive oxygen species antagonist that has been shown to neutralize oxygen radicals specifically lowering the overproduction of superoxide anions regulate the production and level of other inflammatory mediators and increase the synthesis of nitric oxide 4 Sodium pyruvate also increases cellular levels of glutathione a major cellular antioxidant which is reduced dramatically in antigen-induced lung disease patients 5
In pilot studies in mild asthmatic subjects it was demonstrated that inhalation of low doses 05 mM of nebulized sodium pyruvate decreased expired hydrogen peroxide by 30 at four hours compared to inhalation of a nebulized saline control These subjects also experienced increased pulmonary function as determined by FEV1 128 and PEF 345 measurements after four hours referenced in Cellular Sciences IND 50089 It is theorized that the reactive oxygen species antagonist properties of sodium pyruvate reduced the production of oxygen radicals including hydrogen peroxide and increased the levels of nitric oxide Together this led to reduced inflammation and lung damage and increased lung function through improved bronchodilation
In summary it is believed that inhalation of sodium pyruvate will reduce the lung damage resulting from the increase in reactive oxygen species associated with the inflammation component of the disease and will enhances the availability of nitric oxide to produce bronchodilation by enhancing its synthesis and protecting it from destruction by reactive oxygen species
Experimental Clinical Protocol Hypothesis Sodium Pyruvate delivered by nebulization to the lungs produces bronchodilation in asthmatics as measured by FEV1
Intent Provide support for further drug development of nebulized Sodium Pyruvate as a therapeutic agent in asthma
Design Randomized double-blind placebo-controlled cross-over study of 52 completed subjects
Treatment 1 05 mM sodium pyruvate in 09 saline solution 5ml Cellular Sciences CA nebulized via a Pari LC PlusR reusable nebulizer powered by a ProNebR compressor Midlothian VA Treatment 2 Saline 09 5ml Baxter nebulized using the same nebulizer system as above A randomization algorithm using random permuted blocks 4-8 subjects will be used to generate treatment order assignments An unblinded statistician will generate this list of treatment order assignments
Patient Recruitment and Selection The large cohort of potential subjects who have previously participated in asthma studies through our clinical research laboratory will be apprised of the study Patients attending the UCLA Asthma and Cough Center will also be informed of the study Advertisements will be sent by regular mail and by e-mail to physicians participating in the UCLA Healthcare System and to local pulmonologists practicing throughout the Los Angeles area Local Allergists who collaborate with us in common clinical trial protocols will be informed of the study by personalized letter and e-mail Advertisements will be placed in the classified andor health sections of local newspapers A description of the study will be posted on internet sites featuring clinical research trials
Subjects will be recruited until a total of 52 complete the study Assuming a 5 drop-out and non-compliance rate we expect a total of 55 subjects recruited Patient Eligibility Criteria
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None