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

Sponsor:	Ullevaal University Hospital
Collaborator:	University of Oslo
Information provided by:	Oslo University Hospital
ClinicalTrials.gov Identifier:	NCT00921505

Purpose

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	Intervention	Phase
Pain	Drug: Ibuprofen Drug: Paracetamol (acetaminophen) 1000 mg Drug: Paracetamol + ibuprofen	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Crossover Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Oxygen Therapy

Drug Information available for: Ibuprofen Acetaminophen CT 2584

U.S. FDA Resources

Further study details as provided by Oslo University Hospital:

Primary Outcome Measures:

Leukocyte radical oxygen species (ROS) production [ Time Frame: 24 hours for each crossover event ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Platelet activation status [ Time Frame: 24 hours for each crossover event ] [ Designated as safety issue: No ]

Estimated Enrollment:	7
Study Start Date:	May 2009
Study Completion Date:	January 2010
Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Ibuprofen 400 mg Ibuprofen oral single dose	Drug: Ibuprofen Tablet ibuprofen 400 mg oral single dose (1 tablet) Other Names: Ibumetin ibuprofen 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 Ibuprofen 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

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.

Eligibility

Ages Eligible for Study:	18 Years to 35 Years
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00921505

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. Review.

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

Responsible Party:	Professor Torstein Lyberg, Ullevaal University Hospital
ClinicalTrials.gov Identifier:	NCT00921505 History of Changes
Other Study ID Numbers:	PARIBU-024, EudraCT No. 2009-009036-77
Study First Received:	June 15, 2009
Last Updated:	July 3, 2011
Health Authority:	Norway: The National Committees for Research Ethics in Norway; Norway: Norwegian Medicines Agency; Norway: Norwegian Social Science Data Services

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
Antipyretics
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

Central Nervous System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012