Effects of a Cyclic NSAID Regimen on Levels of GCF PGE-E2 and IL-1beta

A Cyclic Regimen of Diclofenac Potassium May be Efficacious in the Management of Chronic Periodontitis in Adults

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for inflammation control and pain relief. However, while adjunct use of NSAIDs is avoided for periodontal therapy because of related side effects, cyclic administration of NSAIDs may reduce or eliminate these effects. The investigators evaluated the effect of a cyclic diclofenac potassium regimen on clinical parameters and levels of prostaglandin E2 (PGE2) and interleukin-1beta (IL-1beta) in the gingival crevicular fluid (GCF) of subjects with periodontitis. Forty-one subjects with moderate to chronic periodontitis (33 men, 8 women) were divided into two groups (test and control) after initial periodontal therapy. During this 6-month, randomized, double-blind, placebo-controlled study, test (n = 28) and control (n = 13) groups were administered a cyclic regimen of diclofenac potassium (50 mg, twice daily) or placebo. Clinical measurements of disease severity and GCF sample collections were made at baseline, 2, 4 and 6 months. GCF levels of PGE2 and IL1-1beta were determined using EIA and ELISA kits, respectively.

Study Overview

• Status: Completed
• Conditions: Non-steroidal Anti-inflammatory Poisoning
• Intervention / Treatment: Drug: cataflam (diclofenac potassium); Drug: placebo

Detailed Description

Study Design This study utilized a randomized, controlled, double-blind, parallel-group design to investigate the 6-month effect of a cyclic regimen of diclofenac potassium [50 mg, twice daily (b.i.d)] on clinical parameters of periodontal disease and levels of PGE2 and IL-1beta in GCF. After clinical and radiographic examination, subjects were divided into two groups: 28 patients in the test group and 13 patients in the control group. Of the 28 patients in the test group, ten (nine men, one woman) were smokers, eleven (six women, five men) were non-smokers, and seven (all men) were ex-smokers. Thirteen patients in the control group comprised six smokers (five men, one woman), five non-smokers (four women, one man) and two ex-smokers (both men).

Test and control groups were administered either diclofenac potassium (50 mg) or placebo gel caps (containing inactive filler of starch flour and carboxymethylcellulose), respectively, b.i.d. after a meal for 6 months in a cyclic regimen. Administration of diclofenac potassium or placebo was undertaken from baseline to 2 months, no drug (diclofenac potassium or placebo) was administered from 2 to 4 months, then diclofenac potassium or placebo therapy was reinstituted (b.i.d.) from 4 to 6 months. To promote compliance, each patient was recalled monthly. Patients in both groups were instructed on oral hygiene, including tooth brushing for at least 2 minutes (b.i.d.) and daily interdental cleaning. SRP was not carried out during these recalls. During the screening period (baseline as well as 2, 4 and 6 months), all subjects underwent physical examinations and biochemical analyses (blood chemistry, complete blood count, urinalyses and pregnancy testing).

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 32 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• with moderate to chronic periodontal disease
• (at least two sites with loss of clinical attachment > 4mm
• alveolar bone loss of 30-50%, as judged by radiography
• received initial periodontal therapy, including scaling and root planning, as well as oral hygiene instruction less than six weeks before study commencement.

Exclusion Criteria:

• history of cardiovascular disease, renal disease, bleeding in the upper gastrointestinal tract, gastrointestinal ulcers, asthma, hypersensitivity to diclofenac or other NSAIDs, prosthetic joint replacement, or other chronic disease affecting compliance
• received antibiotics or antibacterial agents less than 6 months before study commencement
• received NSAIDs within 1 month, or phenytoin or calcium antagonists within 3 months
• history of pregnancy, lactation, or inadequate birth control

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: diclofenac potassium; Cataflam (diclofenac potassium, 50 mg) b.i.d. after a meal for 6 months in a cyclic regimen. Administration of diclofenac potassium was undertaken from baseline to 2 months, no drug (diclofenac potassium) was administered from 2 to 4 months, then diclofenac potassium therapy was reinstituted (b.i.d.) from 4 to 6 months. To promote compliance, each patient was recalled monthly.	Drug: cataflam (diclofenac potassium); Cataflam (diclofenac potassium, 50 mg) b.i.d. after a meal for 6 months in a cyclic regimen. Administration of diclofenac potassium was undertaken from baseline to 2 months, no drug (diclofenac potassium or placebo) was administered from 2 to 4 months, then diclofenac potassium or placebo therapy was reinstituted (b.i.d.) from 4 to 6 months. To promote compliance, each patient was recalled monthly.; Other Names: Cataflam
Active Comparator: placebo; or placebo gel caps (containing inactive filler of starch flour and carboxymethylcellulose) b.i.d. after a meal for 6 months in a cyclic regimen. Administration of placebo was undertaken from baseline to 2 months, no drug (placebo) was administered from 2 to 4 months, then diclofenac potassium therapy was reinstituted (b.i.d.) from 4 to 6 months. To promote compliance, each patient was recalled monthly.	Drug: placebo; Placebo gel caps (containing inactive filler of starch flour and carboxymethylcellulose) b.i.d. after a meal for 6 months in a cyclic regimen. Administration of placebo was undertaken from baseline to 2 months, no drug (diclofenac potassium or placebo) was administered from 2 to 4 months, then diclofenac potassium or placebo therapy was reinstituted (b.i.d.) from 4 to 6 months. To promote compliance, each patient was recalled monthly.; Other Names: placebo gel cap

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in gingival crevicular fluid levels of prostaglandin E2 by 50 mg diclofenac potassium administration	Administration of diclofenac potassium or placebo was undertaken from baseline to 2 months, no drug (diclofenac potassium or placebo) was administered from 2 to 4 months, then diclofenac potassium or placebo therapy was reinstituted (b.i.d.) from 4 to 6 months. Gingival crevicular fluid levels of prostaglandin E2 was measured by using ELISA method, at baseline, 2-month, 4-month and 6-month of the study period.	Baseline, 2 months, 4 months and 6 months
Changes in gingival crevicular fluid levels of interleukin-1beta by 50 mg diclofenac potassium administration	administration of diclofenac potassium or placebo was undertaken from baseline to 2 months, no drug (diclofenac potassium or placebo) was administered from 2 to 4 months, then diclofenac potassium or placebo therapy was reinstituted (b.i.d.) from 4 to 6 months. Gingival crevicular fluid levels of interleukin-1beta were measured by using ELISA method, at baseline, 2-month, 4-month and 6-month of the study period.	Baseline, 2 months, 4 months and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in plaque index (PI) by 50 mg diclofenac potassium administration	At baseline, 2-, 4- and 6-month, plaque index (PI) were recorded. Plaque index (PI); 0: no visible plaque, 1: minor plaque accumulation during probing, 2: visible plaque near by gingiva, 3: full plaque accumulation of the tooth.	Baseline, 2 months, 4 months and 6 months
Changes in gingival index (GI) by 50 mg diclofenac potassium administration	At baseline, 2-, 4- and 6-month, gingival index (GI) were recorded. Gingival index (GI); 0: healthy gingiva, 1: slightly inflammation and no bleeding on probing, 2: moderate gingival inflammation and bleeding on probing, 3: spontaneous bleeding and/or suppuration.	Baseline, 2 months, 4 months and 6 months
Changes in probing depth (PD) by 50 mg diclofenac potassium administration	At baseline, 2-, 4- and 6-month, probing depth (PD) were recorded. Probing depth (PD): with William's periodontal probe, distance between gingival margin to bottom of the sulcus).	Baseline, 2 months, 4 months and 6 months
Changes in probing clinical attachment level by 50 mg diclofenac potassium administration	At baseline, 2-, 4- and 6-month, clinical attachment level (CAL) were recorded. Clinical attachment level (CAL); with William's periodontal probe, distance between enamel-cement junction to bottom of the sulcus).	Baseline, 2 months, 4 months and 6 months

Collaborators and Investigators

• Sponsor: Baskent University
• Investigators: Principal Investigator: Bahar Füsun Oduncuoğlu, DDSPhD, Baskent University

Study record dates

Study Major Dates

• Study Start: January 1, 2000
• Primary Completion (Actual): December 1, 2004
• Study Completion (Actual): December 1, 2004

Study Registration Dates

• First Submitted: January 9, 2016
• First Submitted That Met QC Criteria: January 19, 2016
• First Posted (Estimate): January 20, 2016

Study Record Updates

• Last Update Posted (Estimate): January 20, 2016
• Last Update Submitted That Met QC Criteria: January 19, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: periodontitis; anti-inflammatory agents
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Poisoning; 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; Diclofenac
• Other Study ID Numbers: 2000/071

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided