Study of the Ability of Clarithromycin to Induce Oxidative Stress
NCT ID: NCT00707330
Last Updated: 2008-08-11
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
26 participants
INTERVENTIONAL
2008-05-31
2008-07-31
Brief Summary
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Detailed Description
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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.
Conditions
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Keywords
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Study Design
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RANDOMIZED
CROSSOVER
SCREENING
NONE
Study Groups
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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
Clarithromycin
Prolonged release tablet, 500 mg, 1 tablet a day for a week
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
Clarithromycin
Prolonged release tablet, 500 mg, 1 tablet a day for a week
Interventions
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Clarithromycin
Prolonged release tablet, 500 mg, 1 tablet a day for a week
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
18 Years
35 Years
MALE
Yes
Sponsors
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Rigshospitalet, Denmark
OTHER
Responsible Party
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Head of Department of Clinical Parmacology
Principal Investigators
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Henrik E Poulsen, dr. med.
Role: PRINCIPAL_INVESTIGATOR
Head of Department, Department of Clinical Pharmacology, Rigshospitalet
Locations
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Department of Clinical Pharmacology Q, Rigshospitalet, Blegdamsvej 9
Kopenhagen O, , Denmark
Countries
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References
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Muhlestein JB, Anderson JL. Infectious serology and atherosclerosis: how burdensome is the risk? Circulation. 2003 Jan 21;107(2):220-2. doi: 10.1161/01.cir.0000043909.78380.a0. No abstract available.
Gupta S, Leatham EW, Carrington D, Mendall MA, Kaski JC, Camm AJ. Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction. Circulation. 1997 Jul 15;96(2):404-7. doi: 10.1161/01.cir.96.2.404.
Gurfinkel E, Bozovich G, Daroca A, Beck E, Mautner B. Randomised trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS Pilot Study. ROXIS Study Group. Lancet. 1997 Aug 9;350(9075):404-7. doi: 10.1016/s0140-6736(97)07201-2.
Jespersen CM, Als-Nielsen B, Damgaard M, Hansen JF, Hansen S, Helo OH, Hildebrandt P, Hilden J, Jensen GB, Kastrup J, Kolmos HJ, Kjoller E, Lind I, Nielsen H, Petersen L, Gluud C; CLARICOR Trial Group. Randomised placebo controlled multicentre trial to assess short term clarithromycin for patients with stable coronary heart disease: CLARICOR trial. BMJ. 2006 Jan 7;332(7532):22-7. doi: 10.1136/bmj.38666.653600.55. Epub 2005 Dec 8.
Dhalla NS, Temsah RM, Netticadan T. Role of oxidative stress in cardiovascular diseases. J Hypertens. 2000 Jun;18(6):655-73. doi: 10.1097/00004872-200018060-00002.
Kohanski MA, Dwyer DJ, Hayete B, Lawrence CA, Collins JJ. A common mechanism of cellular death induced by bactericidal antibiotics. Cell. 2007 Sep 7;130(5):797-810. doi: 10.1016/j.cell.2007.06.049.
Other Identifiers
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EudraCT 2008-001299-61
Identifier Type: -
Identifier Source: secondary_id
VEK H-D-2008-026
Identifier Type: -
Identifier Source: secondary_id
DKMA 2612-3720
Identifier Type: -
Identifier Source: secondary_id
Datatilsynet 2008-41-2030
Identifier Type: -
Identifier Source: secondary_id
3-12-1-18-15-23
Identifier Type: -
Identifier Source: org_study_id