Ignite Creation Date:
2024-05-05 @ 4:43 PM
Last Modification Date:
2024-10-26 @ 9:23 AM
Study NCT ID:
NCT00308243
Status:
COMPLETED
Last Update Posted:
2011-07-19
First Post:
2006-03-27
Brief Title:
Inhaled Sodium Pyruvate for the Treatment of Cystic Fibrosis
Sponsor:
Emphycorp
Organization:
Emphycorp
Study Overview
Official Title:
Inhaled Sodium Pyruvate for the Treatment of Cystic Fibrosis A Phase I Double Blind Placebo Controlled Safety Study Stage 1
Status:
COMPLETED
Status Verified Date:
2011-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
It is hypothesized that the inhalation of sodium pyruvate will reduce lung damage in patients with Cystic Fibrosis CF by its ability to reduce levels of toxic reactive oxygen and nitrogen compounds associated with the chronic inflammatory component of the disease The primary objective of the study is to assess the safety of inhaled sodium pyruvate in 09 sodium chloride saline solution in people with CF Further to determine whether inhaled sodium pyruvate will improve lung function as determined by spirometry or reduced inflammatory markers in induced sputum of people with CF
Detailed Description:
Cystic fibrosis CF is the most common lethal inherited disease of Caucasians Approximately 30000 people in the United States and 70000 worldwide have a diagnosis of CF It is caused by mutations in the cystic fibrosis transmembrane regulator CFTR gene The clinical manifestations characteristic of CF include progressive bronchiectatic lung disease with thick mucus production and colonization by Pseudomonas aeruginosa The CFTR gene mutation results in altered cell transport properties which affect both chloride and glutathione secretion Chronic inflammation associated with activated neutrophils and macrophages is a common feature of CF Highly reactive toxic oxygen superoxide anion free hydroxyl radical hydrogen peroxide and nitrogen species nitric oxide peroxynitrites are abundant in the chronic inflammatory response in CF and appear to play a prominent role in the pathogenesis of this disease These reactive oxygen and nitrogen species have been shown to be directly toxic to various mammalian tissues including lung via DNA damage and cell membrane lipid peroxidation In addition elevated levels of hydrogen peroxide and nitric oxide have been demonstrated in sputum and bronchoalveolar lavage fluid of patients with CF asthma and chronic obstructive pulmonary disease Clearly reactive oxygen and nitrogen species are implicated in the pathogenesis of a variety of lung diseases including CF
Sodium pyruvate is an antagonist of both reactive oxygen and nitrogen species It also has the potential to increase intracellular levels of thiol compounds major sources of intracellular anti-oxidants Sodium pyruvate has been shown to act as an anti-inflammatory agent that can reduce the number of infiltrating neutrophils and levels of oxygen radicals at wound sites thereby limiting the production of pro-inflammatory mediators Thus it is hypothesized that the inhalation of sodium pyruvate will reduce lung damage in patients with CF by its ability to reduce levels of toxic reactive oxygen and nitrogen species associated with the chronic inflammatory component of the disease
The trial is a Phase I Safety Study that will be conducted in three Stages The study is designed to assess the safety of administering sodium pyruvate inhalation therapy to CF subjects once a day for one day then twice a day for one day and finally twice a day for four weeks All testing including the screening visit and Stage 1 and Stages 2 and 3 will be conducted at the University of Minnesota UMN General Clinical Research Center GCRC
Stage 1 - Single dose inhalation - 24 hours n15 Participants with CF will receive a single dose of sodium pyruvate 5 ml in physiological saline via a Pari-Jet hand-held nebulizer Pari LC Plus nebulizer system and will be followed at UMN GRC for four hours with a follow up telephone interview at 24 hours Three concentrations 05 mM 15 mM and 50 mM of sodium pyruvate solution will be studied Five subjects will receive the lowest concentration of sodium pyruvate solution then another five subjects will receive the middle dose of sodium pyruvate solution and finally a third group of five subjects will receive the highest dose of sodium pyruvate solution
Patients enrolled in Stage 1 will have one 6-hour visit at UMN GCRC Following administration of a single 5-mL dose of either 05 mM 15 mM or 50 mM sodium pyruvate in 09 saline solution the following tests will be performed
Post Inhalation of Study Drug
Spirometry
Post inhalation 05 Hr
Post inhalation 1 Hr
Post inhalation 2 Hr
Post inhalation 4 Hr
Sputum Induction
Post inhalation 1 Hr
SaO2
Post inhalation 05 Hr
Post inhalation 1 Hr
Post inhalation 2 Hr
Post inhalation 4 Hr
End of Visit
Blood and Urine Analysis
Post inhalation 4 Hr
Electrocardiogram
Post inhalation 4 Hr
Vital Signs
Post inhalation 4 Hr
The parameters for safety monitoring will include spirometry vital signs ECG SaO2 and routine blood and urine analysis which will be conducted pre- and post- inhalation of sodium pyruvate Follow up telephone interviews will also be conducted for each stage
With regard to efficacy spirometry and induced sputum samples will be monitored pre- and post- inhalation of sodium pyruvate Induced sputum samples will be evaluated for cellular content total WBC and differential and the fluid content assessed for total protein total DNA elastase glutathione GSH and GSSG H2O2 and inflammatory cytokines IL-1 IL-6 and IL-8 TNF-alpha
Sodium pyruvate is an antagonist of both reactive oxygen and nitrogen species It also has the potential to increase intracellular levels of thiol compounds major sources of intracellular anti-oxidants Sodium pyruvate has been shown to act as an anti-inflammatory agent that can reduce the number of infiltrating neutrophils and levels of oxygen radicals at wound sites thereby limiting the production of pro-inflammatory mediators Thus it is hypothesized that the inhalation of sodium pyruvate will reduce lung damage in patients with CF by its ability to reduce levels of toxic reactive oxygen and nitrogen species associated with the chronic inflammatory component of the disease
The trial is a Phase I Safety Study that will be conducted in three Stages The study is designed to assess the safety of administering sodium pyruvate inhalation therapy to CF subjects once a day for one day then twice a day for one day and finally twice a day for four weeks All testing including the screening visit and Stage 1 and Stages 2 and 3 will be conducted at the University of Minnesota UMN General Clinical Research Center GCRC
Stage 1 - Single dose inhalation - 24 hours n15 Participants with CF will receive a single dose of sodium pyruvate 5 ml in physiological saline via a Pari-Jet hand-held nebulizer Pari LC Plus nebulizer system and will be followed at UMN GRC for four hours with a follow up telephone interview at 24 hours Three concentrations 05 mM 15 mM and 50 mM of sodium pyruvate solution will be studied Five subjects will receive the lowest concentration of sodium pyruvate solution then another five subjects will receive the middle dose of sodium pyruvate solution and finally a third group of five subjects will receive the highest dose of sodium pyruvate solution
Patients enrolled in Stage 1 will have one 6-hour visit at UMN GCRC Following administration of a single 5-mL dose of either 05 mM 15 mM or 50 mM sodium pyruvate in 09 saline solution the following tests will be performed
Post Inhalation of Study Drug
Spirometry
Post inhalation 05 Hr
Post inhalation 1 Hr
Post inhalation 2 Hr
Post inhalation 4 Hr
Sputum Induction
Post inhalation 1 Hr
SaO2
Post inhalation 05 Hr
Post inhalation 1 Hr
Post inhalation 2 Hr
Post inhalation 4 Hr
End of Visit
Blood and Urine Analysis
Post inhalation 4 Hr
Electrocardiogram
Post inhalation 4 Hr
Vital Signs
Post inhalation 4 Hr
The parameters for safety monitoring will include spirometry vital signs ECG SaO2 and routine blood and urine analysis which will be conducted pre- and post- inhalation of sodium pyruvate Follow up telephone interviews will also be conducted for each stage
With regard to efficacy spirometry and induced sputum samples will be monitored pre- and post- inhalation of sodium pyruvate Induced sputum samples will be evaluated for cellular content total WBC and differential and the fluid content assessed for total protein total DNA elastase glutathione GSH and GSSG H2O2 and inflammatory cytokines IL-1 IL-6 and IL-8 TNF-alpha
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| Orphan Drug 02-1656 | None | None | None |