Study of the Ability of Clarithromycin to Induce Oxidative Stress
キーワード
概要
説明
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.
日付
| 最終確認済み: | 07/31/2008 |
| 最初に提出された: | 06/25/2008 |
| 提出された推定登録数: | 06/26/2008 |
| 最初の投稿: | 06/29/2008 |
| 最終更新が送信されました: | 08/07/2008 |
| 最終更新日: | 08/10/2008 |
| 実際の研究開始日: | 04/30/2008 |
| 一次完了予定日: | 06/30/2008 |
| 研究完了予定日: | 06/30/2008 |
状態または病気
介入/治療
Drug: Clarithromycin
段階
アームグループ
| 腕 | 介入/治療 |
|---|---|
| Experimental: 1 Subjects randomised to this arm will first be treated with Clarithromycin for a week, then have a 2-week washout, and finally one week of no treatment | |
| Active Comparator: 2 Subjects randomised to this arm will first receive one week of no treatment, then have a 2-week washout, and finally be treated with Clarithromycin for a week |
適格基準
| 研究の対象となる年齢 | 18 Years に 18 Years |
| 研究に適格な性別 | Male |
| 健康なボランティアを受け入れる | はい |
| 基準 | Inclusion Criteria: - Caucasian - Non-smoker - Body mass index (BMI) must be ≥18 and ≤ 30 - Blood pressure must be within the following limits: - Systolic blood pressure (110 mmHg > X < 140 mmHg) - Diastolic blood pressure (60 mmHg > Y < 90 mmHg) - Normal lipid plasma levels: - Total cholesterol (≤ 6,0 mmol/l) - HDL-cholesterol (≥ 0,9 mmol/l) - LDL-cholesterol (≤ 4,5 mmol/l) - Triglycerides (0,5-2,2 mmol/l) Exclusion Criteria: - Smokers - CRP: > 10 mg/l - Prolonged QT interval (defined as QTc > 450 msec.) - Severe renal insufficiency (Cpl (creatinine) > 0100 mmol/l) - Hereditary galactose intolerance - A special form of hereditary lactase deficiency (Lapp Lactase deficiency) - Glucose/galactose malabsorption - Use of medicines and herbal remedies that affect/is affected by Clarithromycin, or lead to QT prolongation, for example, cisapride, pimozide, terfenadine, ergotamine, dihydroergotamine, fluconazole, ritonavir, carbamazepine, kinidin, disopyramide, lovastatin, simvastatin, warfarin, acenocoumarol, sildenafil, Tadalafil, vardenafil, theophylline, tolterodine, triazolo benzodiazepins, omeprazole, colchinine, digoxin, zidovudine, phenytoin, valproat, atazanavir, itraconazole, saquinavir - Inborn condition with prolonged QT interval - The following disorders: - Coronary artery disease - Former cardiac arrhythmias - Severe heart insufficiency - Non-compensated hypokalemia (defined as Cpl (K) < 3.2 mmol/ l) and/or hypomagnesemia (defined as Cpl (Mg) < 0.67 mmol/l) - Bradycardia ( < 50 bpm) - Known allergy to clarithromycin or other macrolides - Narcotic - Eating food supplements |
結果
主な結果の測定
1. Amount of 8-oxo-deoxyguanine in 24 hour-urine measured in nmol/mmol creatinine [End of study (July-August 2008)]
2. Amount of Malondialdehyde in plasma [End of study (July-August 2008)]
二次的な結果の測定
1. Amount of Total Vitamin C (Ascorbic acid) in plasma [End of study (July-August 2008)]
2. Caffeine-metabolite ratio in 24 hour-urine [End of Study (July-August 2008)]
