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

• ClinicalTrials.gov Identifier: NCT00921505
• Recruitment Status: Completed
• First Posted: June 16, 2009
• Last Update Posted: July 6, 2011
• Sponsor: Ullevaal University Hospital
• Collaborator: University of Oslo
• Information provided by: Oslo University Hospital

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Pain	Drug: Ibuprofen; Drug: Paracetamol (acetaminophen) 1000 mg; Drug: Paracetamol + ibuprofen	Phase 4

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 7 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: The Effect of Ibuprofen, Paracetamol and Their Combination on Reactive Oxygen Species (ROS)- Production in Leukocytes and Platelet Activation
• Study Start Date: May 2009
• Actual Primary Completion Date: January 2010
• Actual Study Completion Date: January 2010

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Ibuprofen 400 mg; Ibuprofen oral single dose	Drug: Ibuprofen; Tablet ibuprofen 400 mg oral single dose (1 tablet); Other Names: Ibumetin; ATC code: M01A E01
Active Comparator: Ibuprofen 1200 mg; Ibuprofen oral single dose	Drug: Ibuprofen; Tablets (2 x 600 mg) oral single dose (2 tablets); Other Names: Ibumetin; ATC code: M01A E01
Active Comparator: Paracetamol (acetaminophen) 1000 mg; Paracetamol (acetaminophen) oral single dose	Drug: Paracetamol (acetaminophen) 1000 mg; Tablets (2 x 500 mg) oral single dose (2 tablets); Other Names: Paracetamol; Acetaminophen; ATC code: N02B E01
Active Comparator: Ibuprofen 400 mg + paracetamol 1000 mg; Paracetamol (acetaminophen) + ibuprofen oral single dose	Drug: Paracetamol + ibuprofen; Tablets (ibuprofen 400 mg + paracetamol (acetaminophen) 2 x 500 mg) single oral dose (3 tablets); Other Names: Ibumetin; Ibuprofen; ATC code: M01A E01; Paracetamol; Acetaminophen; ATC code: N02B E01

Outcome Measures

Primary Outcome Measures :

1. Leukocyte radical oxygen species (ROS) production [ Time Frame: 24 hours for each crossover event ]

Secondary Outcome Measures :

1. Platelet activation status [ Time Frame: 24 hours for each crossover event ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 35 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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).

Contacts and Locations

Locations

Norway

Ullevaal University Hospital

Oslo, Norway, NO-0407

Sponsors and Collaborators

Ullevaal University Hospital

University of Oslo

Investigators

• Study Director: Torstein Lyberg, DDS, MD; Ullevaal University Hospital

More Information

Publications:

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.

Nagata M. Inflammatory cells and oxygen radicals. Curr Drug Targets Inflamm Allergy. 2005 Aug;4(4):503-4. doi: 10.2174/1568010054526322.

Nielsen VG, Webster RO. Inhibition of human polymorphonuclear leukocyte functions by ibuprofen. Immunopharmacology. 1987 Feb;13(1):61-71. doi: 10.1016/0162-3109(87)90027-0.

• Responsible Party: Professor Torstein Lyberg, Ullevaal University Hospital
• ClinicalTrials.gov Identifier: NCT00921505
• Other Study ID Numbers: PARIBU-024; EudraCT No. 2009-009036-77
• First Posted: June 16, 2009
• Last Update Posted: July 6, 2011
• Last Verified: March 2009

Keywords provided by Oslo University Hospital:

Acetaminophen; Ibuprofen; Platelets; Leukocytes; Oxygen species; Humans; Blood Platelets; Reactive Oxygen Species; Platelet Activation

Additional relevant MeSH terms:

Acetaminophen; Ibuprofen; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Antipyretics; Anti-Inflammatory Agents, Non-Steroidal; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action