Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT00262652 |
| Other study ID # |
CSI-UCLA-ASTHMA-01 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
Phase 1/Phase 2
|
| First received |
December 6, 2005 |
| Last updated |
June 24, 2011 |
| Start date |
January 2006 |
| Est. completion date |
September 2006 |
Study information
| Verified date |
November 2005 |
| Source |
Emphycorp |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
United States: Food and Drug Administration |
| Study type |
Interventional
|
Clinical Trial 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.
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 (0.5 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 (+12.8%) and PEF (+34.5%)
measurements after four hours (referenced in Cellular Sciences IND #50,089). 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: 0.5 mM sodium pyruvate in 0.9% saline solution, (5ml) (Cellular Sciences, CA)
nebulized via a Pari LC Plus(R) reusable nebulizer powered by a ProNeb(R) compressor
(Midlothian, VA) Treatment 2: Saline 0.9%, (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 and/or 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
