Study of the Ability of Clarithromycin to Induce Oxidative Stress
Condition: Oxidative Stress
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of the study is to examine whether Klacid® (Clarithromycin) will induce oxidative
      stress (stress from oxygen) in healthy subjects. This is done by measuring the content of a
      particular substance in the urine sample, which is released when the body is exposed to
      oxidative stress. In addition, there will also be taken blood samples, which is analysed for
      another substance that is indicative of oxidative stress.
    

Detailed description: 
      The purpose of the study is to examine whether Klacid® induce oxidative stress in healthy
      subjects.

      Many studies have shown that atherosclerosis can cause acute myocardial infarction (AMI). The
      development of atherosclerosis is exacerbated by simultaneous infection with Chlamydophila
      pneumoniae, and its accompanying inflammation. There has been shown a positive association
      between Chlamydophila pneumoniae antibodies and the incidence of cardiovascular
      complications, suggesting that Chlamydophila pneumoniae could exacerbate the development of
      atherosclerosis [1]. It has therefore been tried to treat atherosclerotic AMI- patients
      prophylactically with macrolide antibiotics (which is used to treat Chlamydia infections), to
      halt development of the atherosclerosis and the accompanying risk of a new acute myocardial
      infarction.

      Two minor studies have demonstrated a positive effect of macrolide-treatment, why a major
      Danish study of Clarithromycin was implemented [2-4]. Clarithromycin treatment was tested
      against placebo in 4373 atherosclerotic patients who had had an AMI. It appeared that the use
      of clarithromycin led to an increased cardiovascular mortality, which could not be explained
      [4]. The finding of the study suggests that clarithromycin cannot be used for secondary
      prophylaxis of cardiovascular complications, but whether clarithromycin can be used for
      primary prophylaxis is not known.

      It has been shown that oxidative stress can participate in the development of cardiovascular
      complications [5], and it could be such an oxidative stress that had led to the increased
      mortality in the above study. Especially because a recent american study found evidence that
      bactericidal antibiotics induce oxidative stress in bacteria, leading to cell death [6]. This
      oxidative stress contributes significantly to the impact of the bactericidal antibiotics,
      which was thought to be primarily attributed to their specific drug/target interactions. The
      same study also examined erythromycin, from which clarithromycin is a derivate. Erythromycin
      showed no induction of oxidative stress, but clarithromycin is twice as effective as
      erythromycin, which could be due to oxidative stress caused by clarithromycin.

      This study seeks to clarify a possible mechanism for clarithromycin, by an examination on
      healthy volunteers without atherosclerosis.
    

Intervention name(s): Clarithromycin
Intervention type(s): Drug
Intervention description(s): Prolonged release tablet, 500 mg, 1 tablet a day for a week
Other intervention name(s): Klacid Uno; ATC: J01FA09
Intervention MeSH terms: Clarithromycin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Screening
Keywords: oxidative stress; 8-oxo-deoxyguanine; 8-oxodG; clarithromycin; malondialdehyde; mda; vitamine C; ascorbic acid