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

Tracking Information

• First Submitted Date: June 15, 2009
• First Posted Date: June 16, 2009
• Last Update Posted Date: July 6, 2011
• Study Start Date: May 2009
• Actual Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 15, 2009): Leukocyte radical oxygen species (ROS) production [ Time Frame: 24 hours for each crossover event ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: June 15, 2009): Platelet activation status [ Time Frame: 24 hours for each crossover event ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effect of Ibuprofen, Paracetamol and Their Combination on Radical Oxygen Species (ROS) Production
• Official Title: The Effect of Ibuprofen, Paracetamol and Their Combination on Reactive Oxygen Species (ROS)- Production in Leukocytes and Platelet Activation
• 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.
• 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 Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Non-Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Pain

Intervention

• Drug: Ibuprofen
  Tablet ibuprofen 400 mg oral single dose (1 tablet)
  Other Names:

  • Ibumetin
  • ATC code: M01A E01
• Drug: Ibuprofen
  Tablets (2 x 600 mg) oral single dose (2 tablets)
  Other Names:

  • Ibumetin
  • ATC code: M01A E01
• Drug: Paracetamol (acetaminophen) 1000 mg
  Tablets (2 x 500 mg) oral single dose (2 tablets)
  Other Names:

  • Paracetamol
  • Acetaminophen
  • ATC code: N02B E01
• 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

Study Arms

• Active Comparator: Ibuprofen 400 mg
  Ibuprofen oral single dose
  Intervention: Drug: Ibuprofen
• Active Comparator: Ibuprofen 1200 mg
  Ibuprofen oral single dose
  Intervention: Drug: Ibuprofen
• Active Comparator: Paracetamol (acetaminophen) 1000 mg
  Paracetamol (acetaminophen) oral single dose
  Intervention: Drug: Paracetamol (acetaminophen) 1000 mg
• Active Comparator: Ibuprofen 400 mg + paracetamol 1000 mg
  Paracetamol (acetaminophen) + ibuprofen oral single dose
  Intervention: Drug: Paracetamol + ibuprofen

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.

Recruitment Information

• Recruitment Status: Completed
• Estimated Enrollment (submitted: June 15, 2009): 7
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: January 2010
• Actual Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)

Eligibility 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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 35 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Norway

Administrative Information

• NCT Number: NCT00921505
• Other Study ID Numbers: PARIBU-024; EudraCT No. 2009-009036-77
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Professor Torstein Lyberg, Ullevaal University Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Ullevaal University Hospital
• Original Study Sponsor: Same as current
• Collaborators: University of Oslo

Investigators

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

• PRS Account: Oslo University Hospital
• Verification Date: March 2009