Clinical trial NCT00992667: Inhaled Apocynin Decreases Reactive Oxygen Species Concentrations in Exhaled Breath Condensate in Mild Asthmatics
Official title: Inhaled Apocynin Decreases Reactive Oxygen Species Concentrations in Exhaled Breath Condensate in Mild Asthmatics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bronchial Asthma
Keywords: apocynin
asthma
Lead sponsor: Medical University of Lodz
Sponsor class: OTHER
Collaborators: name: Ministry of Science and Higher Education, Poland
First posted: 2009-10-09
Enrollment: 10
Sex: ALL
Minimum age (years): 22
Maximum age (years): 56
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The aim of the study is to investigate the effect of inhaled apocynin on ROS (reactive oxygen species) and NOS (reactive nitrogen species) synthesis in 10 nonsmoking mild asthmatics. Effects of nebulized apocynin (0.5 mg/ml, 6 ml) are assessed in exhaled breath condensate (EBC) after 30, 60 and 120 minutes.

Detailed description: The study had a double-blind, placebo-controlled, cross-over design, consisted of 2 visits, separated 30 ± 10 days. If during the first visit the drug was used, in the second visit - placebo or vice versa. Before and after procedure, safety measures (arterial blood pressure, heart rate value, and cough scale) were performed. The effect of a possible inhibitor of ROS formation was performed using corticosteroid-naive asthmatic subjects, which are more prone to oxidative stress than healthy non-smoking subjects. The study protocol was approved by the Ethics Committee of Medical University of Lodz (no. RNN/12/08/KE) and written consent was obtained from every subject prior to the study.

EBC was collected using a modification of the method described previously by Doniec et al.2005. The subjects breathed spontaneously through a mouthpiece for 20 min. Each subject wore a nose clip during this procedure. Approximately 2 ml of condensate was collected and immediately stored at -80°C until the procedure of H2O2, NO2- and NO3- measurement.

6 ml of apocynin of total dose 3 mg (0.5 mg/ml) has been nebulized through the mouthpiece with using of a nose clip.

The H2O2 concentration in EBC was measured according to the method applied previously by Nowak et al.2001. Determination of NO2- and NO3- with Griess solution was performed by micromethod, carried out in 96-well plates, according to Griess' method, modified the method described by Dziedzic et al.2003.

Eligibility criteria: Inclusion Criteria:

* patients suffering from bronchial asthma (mild)
* patients free of any medication at least 7 days before research
* patients had not suffered from any infectious diseases including upper respiratory tract infections for at least 3 months prior to the study

Exclusion Criteria:

* patients suffering from moderate or severe asthma
* patients taking medication 7 or less days before the study
* infectious diseases that had occurred 3 months or less before the study

Primary outcomes:
measure: blood pressure, peripheral blood differential count, lung functional tests, single breath carbon monoxide diffusing capacity
timeFrame: 6 months
Secondary outcomes:
measure: determination of H2O2, NO2- and NO3- concentrations in exhaled breath condensate, determination of NO2 concentration in serum, blood pressure, peripheral blood differential count, lung functional tests, single breath carbon monoxide diffusing capacity
timeFrame: 6 months
Other outcomes:
Locations:
city: Lodz
country: Poland
facility: Medical University of Lodz
state: Lodzkie
Study officials:
affiliation: Medical University of Lodz
name: Rafal Pawliczak, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Bateman ED, Hurd SS, Barnes PJ, Bousquet J, Drazen JM, FitzGerald JM, Gibson P, Ohta K, O'Byrne P, Pedersen SE, Pizzichini E, Sullivan SD, Wenzel SE, Zar HJ. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J. 2008 Jan;31(1):143-78. doi: 10.1183/09031936.00138707.
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citation: Peters EA, Hiltermann JT, Stolk J. Effect of apocynin on ozone-induced airway hyperresponsiveness to methacholine in asthmatics. Free Radic Biol Med. 2001 Dec 1;31(11):1442-7. doi: 10.1016/s0891-5849(01)00725-0.
citation: Nowak D, Kalucka S, Bialasiewicz P, Krol M. Exhalation of H2O2 and thiobarbituric acid reactive substances (TBARs) by healthy subjects. Free Radic Biol Med. 2001 Jan 15;30(2):178-86. doi: 10.1016/s0891-5849(00)00457-3.
citation: Gage MC, Thippeswamy T. Inhibitors of Src Family Kinases, Inducible Nitric Oxide Synthase, and NADPH Oxidase as Potential CNS Drug Targets for Neurological Diseases. CNS Drugs. 2021 Jan;35(1):1-20. doi: 10.1007/s40263-020-00787-5. Epub 2021 Jan 30.