Study of the Ability of Clarithromycin to Induce Oxidative Stress

NCT00707330 | Completed Phase 1

• 5 other identifiers: 3-12-1-18-15-23EudraCT 2008-001299-61VEK H-D-2008-026DKMA 2612-3720Datatilsynet 2008-41-2030
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Oxidative Stress

Keywords

oxidative stress; 8-oxo-deoxyguanine; 8-oxodG; clarithromycin; malondialdehyde; mda; vitamine C; ascorbic acid

Outcome Measures

Primary Outcomes (2)

• Amount of 8-oxo-deoxyguanine in 24 hour-urine measured in nmol/mmol creatinine

  End of study (July-August 2008)

• Amount of Malondialdehyde in plasma

  End of study (July-August 2008)

Secondary Outcomes (2)

• Amount of Total Vitamin C (Ascorbic acid) in plasma

  End of study (July-August 2008)

• Caffeine-metabolite ratio in 24 hour-urine

  End of Study (July-August 2008)

Study Arms (2)

1

EXPERIMENTAL

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

2

ACTIVE COMPARATOR

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

Interventions

Clarithromycin DRUG

Prolonged release tablet, 500 mg, 1 tablet a day for a week

Also known as: Klacid Uno, ATC: J01FA09

1; 2

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

Department of Clinical Pharmacology Q, Rigshospitalet, Blegdamsvej 9

Kopenhagen O, 2100, Denmark

Location

Related Publications (6)

• 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.

  PMID: 12538417 BACKGROUND

• 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.

  PMID: 9244203 BACKGROUND

• 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.

  PMID: 9259655 BACKGROUND

• 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.

  PMID: 16339220 BACKGROUND

• 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.

  PMID: 10872549 BACKGROUND

• 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.

  PMID: 17803904 BACKGROUND

MeSH Terms

Interventions

Clarithromycin

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Henrik E Poulsen, dr. med.

  Head of Department, Department of Clinical Pharmacology, Rigshospitalet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 26, 2008
• First Posted: June 30, 2008
• Study Start: May 1, 2008
• Primary Completion: July 1, 2008
• Study Completion: July 1, 2008
• Last Updated: August 11, 2008

Record last verified: 2008-08

Locations

DK (1)