Study of the Ability of Clarithromycin to Induce Oxidative Stress (CLAROX)

August 8, 2008 updated by: Rigshospitalet, Denmark

A Randomized, Single Blinded, Open-Label Crossover-Study of the Possible Induction of Oxidative Stress by Clarithromycin in Healthy Subjects

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Kopenhagen O, Denmark, 2100
        • Department of Clinical Pharmacology Q, Rigshospitalet, Blegdamsvej 9

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 35 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: SCREENING
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Drug: Clarithromycin
Prolonged release tablet, 500 mg, 1 tablet a day for a week
Other Names:
  • Klacid Uno
  • ATC: J01FA09
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
Drug: Clarithromycin
Prolonged release tablet, 500 mg, 1 tablet a day for a week
Other Names:
  • Klacid Uno
  • ATC: J01FA09

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Amount of 8-oxo-deoxyguanine in 24 hour-urine measured in nmol/mmol creatinine
Time Frame: End of study (July-August 2008)
End of study (July-August 2008)
Amount of Malondialdehyde in plasma
Time Frame: End of study (July-August 2008)
End of study (July-August 2008)

Secondary Outcome Measures

Outcome Measure
Time Frame
Amount of Total Vitamin C (Ascorbic acid) in plasma
Time Frame: End of study (July-August 2008)
End of study (July-August 2008)
Caffeine-metabolite ratio in 24 hour-urine
Time Frame: End of Study (July-August 2008)
End of Study (July-August 2008)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rigshospitalet, Denmark

Investigators

  • Principal Investigator: Henrik E Poulsen, dr. med., Head of Department, Department of Clinical Pharmacology, Rigshospitalet

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2008

Primary Completion (ACTUAL)

July 1, 2008

Study Completion (ACTUAL)

July 1, 2008

Study Registration Dates

First Submitted

June 26, 2008

First Submitted That Met QC Criteria

June 27, 2008

First Posted (ESTIMATE)

June 30, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

August 11, 2008

Last Update Submitted That Met QC Criteria

August 8, 2008

Last Verified

August 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3-12-1-18-15-23
  • EudraCT 2008-001299-61
  • VEK H-D-2008-026
  • DKMA 2612-3720
  • Datatilsynet 2008-41-2030

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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