NSAID Treatment in Knee Osteoarthritis (NSKO)

EFFECTS OF NSAIDs ON CLINICAL OUTCOMES, SYNOVIAL FLUID CYTOKINE CONCENTRATION AND SIGNAL TRANSDUCTION PATHWAYS IN KNEE OSTEOARTHRITIS

Central mechanisms may play a role in pain perception during osteoarthritis (OA).Local inflammation (which involves production of pro-inflammatory cytokines such as interleukin (IL) 4 TNF-alpha, IL-6 and IL-8) is considered to be a major source of pain.

Certain therapies that specifically interfere with the expression or actions of pro-inflammatory cytokines have been explored. NSAIDs have analgesic, antipyretic and anti-inflammatory properties and are extensively prescribed for several musculoskeletal disorders. Indeed, the Osteoarthritis Research Society International (OARSI) recently recommended the use of NSAIDs for management of knee and hip OA in symptomatic patients. These drugs have been shown to influence cytokine metabolism in the synovial fluid of OA patients with satisfactory relief of painful osteoarthritic joints.

The aim of the current study was to explore whether NSAID treatment inhibits TNF-alpha, IL-6, IL-8, and VEGF secretion in the synovial fluid of osteoarthritic joints. In particular, diclofenac, ibuprofen and celecoxib were studied. Under the hypothesis that relationships between proinflammatory cytokines and the clinical status of OA patients are possible, we also evaluated the association between the concentration of these molecules in the osteoarthritic knee synovial fluid and the pain and functional status of patients with OA. The effects of NSAIDS on signal transduction pathways in the synovial membrane were also investigated.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: Diclofenac; Drug: Ibuprofen; Drug: Celecoxib

Detailed Description

not desired

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Catanzaro, Italy, 88100
    • Department of Orthopedic and Trauma Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients eligible for the study were:

• older than 50 years and
• had primary knee OA diagnosed according to the clinical and radiological criteria of the American Rheumatism Association.

Further inclusion criteria were:

• clinical signs of joint inflammation (warmth, swelling or effusion) and
• a disease severity grade 2 or 3 according to the Kellgren-Lawrence classification

Exclusion Criteria:

• allergy to NSAIDs,
• progressive serious medical conditions (such as cancer, AIDS or end-stage renal disease),
• history of gastrointestinal ulcer or bleeding,
• a hemoglobin concentration lower than 11.5 g/dL,
• renal diseases (serum creatinine concentration more than 1.2 times the upper limit of the normal range according to the central laboratory definition reference values), or
• liver dysfunction (serum alanine or aspartate transaminase concentrations more than 1.5 times the upper limit of normal range according to the central laboratory definition reference values).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: diclofenac 75 mg/day; diclofenac 75 mg once day slow release	Drug: Diclofenac; time of treatment 14 days; Other Names: voltaren
Active Comparator: diclofenac 150 mg/day; diclofenac 75 mg bid	Drug: Diclofenac; time of treatment 14 days; Other Names: voltaren
Active Comparator: ibuprofen 1200 mg/day; ibuprofen 600 mg bid	Drug: Ibuprofen; time of treatment 14 days; Other Names: Brufen
Active Comparator: ibuprofen 1800 mg/day; ibuprofen 600 mg tid	Drug: Ibuprofen; time of treatment 14 days; Other Names: Brufen
Active Comparator: celecoxib 200 mg/day; celecoxib 200 mg once day	Drug: Celecoxib; time of treatment 14 days; Other Names: celebrex
Active Comparator: celecoxib 400 mg/day; celecoxib 200 mg bid	Drug: Celecoxib; time of treatment 14 days; Other Names: celebrex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Western Ontario and McMaster universities (WOMAC) osteoarthritis index score	Womac was used to 77 measure the disease-specific health status of patients before and after the pharmacological treatment.	0-14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Naranjo probability scale	The Naranjo probability scale was used to evaluate the development of adverse drug reaction during this study	14 days

Collaborators and Investigators

• Sponsor: University of Catanzaro
• Investigators: Principal Investigator: Luca Gallelli, MD, University of Catanzaro

Publications and helpful links

General Publications

• Gallelli L, Galasso O, Falcone D, Southworth S, Greco M, Ventura V, Romualdi P, Corigliano A, Terracciano R, Savino R, Gulletta E, Gasparini G, De Sarro G. The effects of nonsteroidal anti-inflammatory drugs on clinical outcomes, synovial fluid cytokine concentration and signal transduction pathways in knee osteoarthritis. A randomized open label trial. Osteoarthritis Cartilage. 2013 Sep;21(9):1400-8. doi: 10.1016/j.joca.2013.06.026.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: May 20, 2013
• First Submitted That Met QC Criteria: May 22, 2013
• First Posted (Estimate): May 23, 2013

Study Record Updates

• Last Update Posted (Estimate): May 23, 2013
• Last Update Submitted That Met QC Criteria: May 22, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: Knee Osteoarthritis
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Celecoxib; Diclofenac; Ibuprofen
• Other Study ID Numbers: LGOG1