Phase I/II Nitric Oxide (NO) Study
Sodium Pyruvate/Nitric Oxide (NO) Pilot Study in Subjects with Lung Disease
 A Phase I controlled pilot clinical trial was designed to determine if a single inhaled dose of sodium pyruvate altered NO levels in expired breath of individuals with COPD (emphysema and chronic bronchitis) or bronchial asthma, and whether this altered level of NO was correlated with improved spirometry values.
Fifteen normal volunteers and sixty subjects with diagnosed lung disease, including emphysema, chronic bronchitis, or bronchial asthma were treated with either a single administration of 0.5 mM, 1.5 mM, or 5.0 mM sodium pyruvate in 0.9% sodium chloride solution (the experimental drug products). Lung function (PEF† and FEV1), expired NO levels, and vital signs were determined prior to administration of the drug products to each subject. Spirometry measurements, expired NO levels, and vital signs were then determined after administration of the drug, and compared to the pre-drug values.
A statistically significant improvement in FEV1 was observed in subjects in the Combined COPD (COPD + Asthma) group (p=0.035), and the Asthma Alone group (p=0.044) 1-hour post inhalation of 0.5 mM sodium pyruvate as compared to the preinhalation value. These changes represented an approximate 5% increase in FEV1. No significant change in the FEV1 was observed in subjects with COPD after the inhalation of sodium pyruvate at either the 1.5 mM or 5.0 mM concentrations.
A significant decrease in expired breath NO levels was observed in subjects in the combined asthma COPD group (p<0.000; 19.0% decrease) and COPD alone group (p=0.003; 24.6% decrease) 1 hour post inhalation of 0.5 mM sodium pyruvate as compared to pre-inhalation values. Figure 4 Also, a significant decrease in expired breath NO levels was observed in subjects in the combined asthma COPD group (p=0.001; 19.4%)), asthma alone group (p=0.008; 16.1% decrease), and the COPD Alone group (p=0.037; 13.6% decrease) 1 hour post inhalation of 1.5 mM sodium pyruvate as compared to preinhalation values. There were no detectable significant changes in expired breath NO levels, FEV1, or PEF after inhalation of the 5.0 mM dose of sodium pyruvate in subjects with COPD as compared to pre-inhalation values. What was noted in these studies was that NO values increased with the inhalation of the 5.0mM concentrations in 55% of the patients by 16%. This is consistent with the literature, that high levels of sodium pyruvate up regulates the synthesis of NO. Figure 4
There were no significant changes observed in normal control subjects after the inhalation of sodium pyruvate, at any of the doses (0.5mM, 1.5mM, and 5.0mM), as compared to preinhalation values for any of the parameters measured. Figure 4
In this study of moderate to severe asthmatics and COPD patients, expired breath NO was reduced in by 24% in 92% of the COPD patients, and in the combined asthmatic COPD group NO was decreased by 19% with 90% of patients obtaining a reduction of NO. 80% of these patients showed a positive FEV. In the 1.5mM concentrations, NO was reduced in 85% of the patients obtaining an overall reduction of NO in the entire group of 20 by 19%. Treating patients with the 5mM concentrations decreased NO levels in only 45% of the patients by 16% with 55% of the patients having an increase in NO production by 13%. The increased production of NO from inhalation of the 5mM concentration did not promote bronchial dilation or bronchial constriction. Again this is new finding that inhaled pyruvate protects NO from becoming peroxynitrite, which decreases FEV1 values. This finding is contrary to literature data that indicated increases in NO tended to decrease FEV1 measurements (40). Figure 4
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