Effect of Ibuprofen, Paracetamol and Their Combination on Radical Oxygen Species (ROS) Production

Pain Clinical Trial

Official title:

The Effect of Ibuprofen, Paracetamol and Their Combination on Reactive Oxygen Species (ROS)- Production in Leukocytes and Platelet Activation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00921505
• Other study ID #: PARIBU-024
• Secondary ID: EudraCT No. 2009
• Status: Completed
• Phase: Phase 4
• First received: June 15, 2009
• Last updated: July 3, 2011
• Start date: May 2009
• Est. completion date: January 2010

Study information

• Verified date: March 2009
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Norway:National Committee for Medical and Health Research EthicsNorway: Norwegian Medicines AgencyNorway: Norwegian Social Science Data Services
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether paracetamol, ibuprofen or their combination can modify generation of radical oxygen species (ROS) from stimulated neutrophils.

Description:

Non-steroidal anti-inflammatory drugs (NSAID) are used to alleviate clinical inflammatory symptoms (e.g. pain, swelling and reduced function). Leukocytes, upon activation during inflammatory states, generate radical oxygen species (ROS) which primarily are intended for host defence against invading pathogens. Certain NSAID can modify the generation of ROS from stimulated neutrophils ranging form increased production to reduced production. Preliminary experiments in our laboratory have shown that different NSAIDs have opposing effects on the ability of leukocytes (granulocytes and monocytes) to produce ROS upon a standardized stimulus, i.e. phorbol myristate acetate (PMA). Paracetamol has a marked inhibitory effect and ibuprofen has a facilitating effect on ROS production. An inhibitory effect of paracetamol was also seen when examining platelet activation markers, whereas acetylsalicylic acid showed a clear enhancing effect in this respect. We want to examine if intake of paracetamol or ibuprofen in vivo have similar effects on leukocyte ROS production and platelet activation, respectively.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• Volunteers of both sexes (ASA type I).

• Females who are not pregnant or plan conception. (A pregnancy test will be conducted before each test day)

• Persons who have not used analgesics for 3 days prior to the blood sampling.

• Persons without known active peptic ulcer or gastrointestinal bleeding.

• Persons without any known hypersensitivity for NSAIDs.

• Persons under no other drug treatment than contraceptives.

• Age 18 to 35 years of Caucasian origin

Exclusion Criteria:

• Pregnancy during the test period.

• Development of active peptic ulcer during the test period.

• Change in medication status during the test period (after inclusion).

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Pain

Intervention

Drug:
• Ibuprofen
Tablet ibuprofen 400 mg oral single dose (1 tablet)
• Ibuprofen
Tablets (2 x 600 mg) oral single dose (2 tablets)
• Paracetamol (acetaminophen) 1000 mg
Tablets (2 x 500 mg) oral single dose (2 tablets)
• Paracetamol + ibuprofen
Tablets (ibuprofen 400 mg + paracetamol (acetaminophen) 2 x 500 mg) single oral dose (3 tablets)

Locations

Country	Name	City	State
Norway	Ullevaal University Hospital	Oslo

Sponsors (2)

Lead Sponsor	Collaborator
Ullevaal University Hospital	University of Oslo

Country where clinical trial is conducted

Norway, 

References & Publications (3)

Nagata M. Inflammatory cells and oxygen radicals. Curr Drug Targets Inflamm Allergy. 2005 Aug;4(4):503-4. Review. — View Citation

Nielsen VG, Webster RO. Inhibition of human polymorphonuclear leukocyte functions by ibuprofen. Immunopharmacology. 1987 Feb;13(1):61-71. — View Citation

Stritesky Larssen K, Lyberg T. Oxidative status--age- and circadian variations?--a study in leukocytes/plasma. Neuro Endocrinol Lett. 2006 Aug;27(4):445-52. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Leukocyte radical oxygen species (ROS) production		24 hours for each crossover event	No
Secondary	Platelet activation status		24 hours for each crossover event	No