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

• ClinicalTrials.gov Identifier: NCT02658799
• Recruitment Status: Completed
• First Posted: January 20, 2016
• Last Update Posted: January 20, 2016
• Sponsor: Baskent University
• Information provided by (Responsible Party): Nilgün Özlem Alptekin, Baskent University

Tracking Information

• First Submitted Date: January 9, 2016
• First Posted Date: January 20, 2016
• Last Update Posted Date: January 20, 2016
• Study Start Date: January 2000
• Actual Primary Completion Date: December 2004 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 19, 2016)

• Changes in gingival crevicular fluid levels of prostaglandin E2 by 50 mg diclofenac potassium administration [ Time Frame: Baseline, 2 months, 4 months and 6 months ]
  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.
• Changes in gingival crevicular fluid levels of interleukin-1beta by 50 mg diclofenac potassium administration [ Time Frame: Baseline, 2 months, 4 months and 6 months ]
  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.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: January 19, 2016)

• Changes in plaque index (PI) by 50 mg diclofenac potassium administration [ Time Frame: Baseline, 2 months, 4 months and 6 months ]
  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.
• Changes in gingival index (GI) by 50 mg diclofenac potassium administration [ Time Frame: Baseline, 2 months, 4 months and 6 months ]
  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.
• Changes in probing depth (PD) by 50 mg diclofenac potassium administration [ Time Frame: Baseline, 2 months, 4 months and 6 months ]
  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).
• Changes in probing clinical attachment level by 50 mg diclofenac potassium administration [ Time Frame: Baseline, 2 months, 4 months and 6 months ]
  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).

• 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: Effects of a Cyclic NSAID Regimen on Levels of GCF PGE-E2 and IL-1beta
• Official Title: A Cyclic Regimen of Diclofenac Potassium May be Efficacious in the Management of Chronic Periodontitis in Adults
• Brief Summary: 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.

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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Non-steroidal Anti-inflammatory Poisoning

Intervention

• 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 Name: Cataflam
• 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 Name: placebo gel cap

Study Arms

• 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.

  Intervention: Drug: cataflam (diclofenac potassium)
• 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.

  Intervention: Drug: placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 19, 2016): 49
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: December 2004
• Actual Primary Completion Date: December 2004 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 32 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT02658799
• Other Study ID Numbers: 2000/071
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Nilgün Özlem Alptekin, Baskent University
• Study Sponsor: Baskent University
• Collaborators: Not Provided

Investigators

• Principal Investigator: Bahar Füsun Oduncuoğlu, DDSPhD; Baskent University

• PRS Account: Baskent University
• Verification Date: January 2016