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Oxidative StressPhase 1CLAROXNCT00707330

Study of the Ability of Clarithromycin to Induce Oxidative Stress

A Phase 1 study testing Clarithromycin in people with Oxidative Stress, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 35 years, men onlyHealthy volunteers can take part
Conditions the study is for
Oxidative Stress
What is being tested?
Clarithromycin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteDenmark
Study dates
May 2008to Jul 2008
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 35 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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)
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  • 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)

Who cannot join

  • 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)
Show all 18Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Denmark1 site

  • Department of Clinical Pharmacology Q, Rigshospitalet, Blegdamsvej 9

    Kopenhagen O, 2100

Other trials in Denmark

About this study

Official title: 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.

Read the 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.

Being tested
Clarithromycin
Keywords
oxidative stress, 8-oxo-deoxyguanine, 8-oxodG, clarithromycin, malondialdehyde, mda, vitamine C, ascorbic acid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ClarithromycinDrug

    Also called Klacid Uno, ATC: J01FA09

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

Study groups in NCT00707330
Study groupRoleWhat they receive
1ExperimentalSubjects 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
Receives: Drug: Clarithromycin
2Active comparatorSubjects 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
Receives: Drug: Clarithromycin

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: End of study (July-August 2008)

  2. Amount of Malondialdehyde in plasma

    Measured: End of study (July-August 2008)

Secondary outcomes (2)

  1. Amount of Total Vitamin C (Ascorbic acid) in plasma

    Measured: End of study (July-August 2008)

  2. Caffeine-metabolite ratio in 24 hour-urine

    Measured: End of Study (July-August 2008)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jun 2008 (estimated)
  2. Study startMay 2008
  3. Primary completionJul 2008
  4. Study completionJul 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Screening
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00707330
Sponsor's protocol ID
3-12-1-18-15-23
Other IDs
EudraCT 2008-001299-61, VEK H-D-2008-026, DKMA 2612-3720, Datatilsynet 2008-41-2030
Acronym
CLAROX
Status last verified
Aug 2008
First submitted
26 Jun 2008
Last updated
11 Aug 2008
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 12538417

  • 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.

    PubMed 9244203

  • 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.

    PubMed 9259655

  • 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.

    PubMed 16339220

  • 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.

    PubMed 10872549

  • 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.

    PubMed 17803904

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Clarithromycin in people with Oxidative Stress, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Aug 2008. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Amount of 8-oxo-deoxyguanine in 24 hour-urine measured in nmol/mmol creatinine (time frame: End of study (July-August 2008)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00707330, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2008.

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