Use of Topical Subgingival Application of Simvastatin Gel in the Treatment of Peri-Implant Mucositis
Condition: Peri-implant Mucositis
MeSH terms: Mucositis
Study type: Interventional
Phase: Phase 2

Summary: 
      This study seeks to test the recently discovered anti-inflammatory action of statins on
      inflamed mucosa surrounding dental implants.

      Hypothesis: The application of 1.2% simvastatin gel will decrease peri-implant inflammation.

      The pilot study will involve 44 subjects divided into a test and control group. The test
      group shall receive topical simvastatin gel administered around the implant with a blunt
      tipped needle. The control group will receive a placebo.

      Inflammatory state shall be determined at baseline as well as follow up visits at 24 hours, 1
      week, and 1 month by clinical indices of inflammation as well as biochemical markers of
      inflammation gathered from around the implants.
    

Detailed description: 
      Following signing the consent document the following will occur:

        1. Screening Patients will complete standard medical and dental health history forms,
           followed by a study specific screening questionnaire. if the patient is deemed eligible,
           the patient will be examined clinically. The clinical examination will include
           diagnostic procedures typical of an implant recall visit. Initially, the sulcus will be
           probed with a periodontal probe; if bleeding on probing is elicited, then a radiograph
           will be made.

           The following shall be done to screen the patients:

             1. Periapical radiographs of the implant to determine bone loss, if bone loss is found
                the patient will be excluded from the study.

             2. Bleeding on probing will be assessed by using a periodontal probe passed along the
                gingival crevice, and bleeding scores will be assessed passing the probe with a
                force of 0.25 N.

             3. If a woman is of childbearing age and suspected of being pregnant, a urine
                pregnancy test shall be made at this time.

           If the patient exhibits no bleeding on probing, or signs of mesial/distal bone loss
           greater than 1mm from the accepted reference point on the implant system the patient
           will be excluded from the study.

        2. Subject allocation

           Subjects will be assigned with equal allocation into the following groups:

             1. Test group: will receive 0.1 ml prepared Simvastatin in 1.2% (W/V)
                Lecithin/isopropyl palmitate solution (Lipoil®), Poloxamer 407 gel (Polox Gel 20%®)
                applied topically into the peri-implant gingival sulcus using a plastic syringe
                with a blunt cannula.

             2. Control group: will receive a placebo of 0.1 ml 40% (W/V) Lecithin/isopropyl
                palmitate solution (Lipoil®), Poloxamer 407 gel (Polox Gel 20%®) applied topically
                into the peri implant gingival sulcus using a plastic syringe with a blunt cannula.

        3. Baseline measurements Baseline measurements will be made at least 48 hours after
           screening (allowing time for complete hemostasis of peri-implant crevicular mucosa after
           bleeding induced by probing in the screening visit).

           Following baseline measurements, Test and Control interventions will be administered.

           The baseline measurements include the following:

             1. Peri-implant crevicular fluid (PICF) collection: Each implant site will be isolated
                with cotton rolls and light air will be applied over the side to eliminate ambient
                salivary contamination of the PICF sample. Sampling will be done using paper strips
                that are inserted with cotton forceps into the gingival crevice until mild
                resistance is felt. After gingival crevicular fluid (GCF) collection, the volumes
                are immediately quantified using the Periotron 8000 instrument.

             2. Gingival Index: Using the Gingival index by Loe and Sillness 1963, the inflammatory
                state of the buccal, lingual, mesial and distal surfaces of the gingiva will be
                scored using the following score system:

                0= normal gingival without signs of inflammation, no inflammation, no bleeding

                  1. minor inflammation , slight discoloration, minor surface alterations, no
                     bleeding

                  2. moderate inflammation, redness, swelling, bleeding upon probing and under
                     pressure

                  3. strong inflammation, strong redness and swelling, tendency toward spontaneous
                     bleeding, ulcerations After a score is given to each site, the scores will be
                     summed together and divided by 4 to reach an overall score.

             3. Probing depth: Measured by a calibrated periodontal probe at 6 different locations,
                mesiobuccal, midbuccal, distobuccal, distolingual, midlingual, and mesiolingual.

        4. Administration of test and control intervention will be delivered into the peri- implant
           gingival sulcus using a plastic syringe with a blunt cannula following baseline
           measurements. 0.1ml of gel will be administered with a blunt cannula evenly distributed
           in the peri-implant sulcus. The investigator will not know whether the subject is
           receiving the active or control intervention.

        5. Recall appointments and measurements Both Test and Control subjects will be scheduled
           recall visits. Recalls will be done at 24 hours (+ or - 3 hours), 1 week (+ or - 12
           hours), and 1 month (+ or - 11 days).

           On each recall visit, the following procedures will take place:

             1. PICF collection: procedures identical to those performed on the baseline visit

             2. Gingival index recording: Identical to that performed on the baseline visit

             3. probing depth measurement : procedures identical to that performed at the baseline
                visit * these measurements will be made by a blinded investigator

        6. Cytokine analysis Due to study constraints, not all PICF samples collected from subjects
           will be analyzed in the pilot study. The samples that will be analyzed will be selected
           randomly from the study population. Cytokine samples from only 13 randomly selected
           subjects from the test group, as well as 13 randomly selected subjects from the control
           group will be analyzed. Of these randomly selected samples, only those collected at
           baseline, 24 hours, and at 1 week will be analyzed. The remaining cytokine samples will
           be evaluated as part of a later study. Cytokine quantities will be determined using; a
           commercial 22 multipixed fluorescent bead based immunoassay and luminex 100 IS
           instrument. The kit used is the MILLIPLEX map Human Cytokine/ Chemokine Magnetic Bead
           Panel- Immunology Multiplex Assay (HCYTOMAG-60K) capable of detecting IL-1Beta;,
           TNF-Alpha;, IL-6, IL-8.

      The study in total will take 1 month and 2 days. All visits will generally take 0.5-1.5
      hours. No long term follow up will be required.
    

Intervention name(s): Simvastatin; Placebo
Intervention type(s): Drug; Other
Intervention description(s): One topical application in peri-implant gingival crevice; One topical application in peri-implant gingival crevice
Other intervention name(s): Simvastatin Powder U.S.P.; Lecithin/isopropyl palmitate solution, Poloxamer 407 gel; Lipoil®, Polox Gel 20%®
Intervention MeSH terms: Simvastatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: topical; subgingival; simvastatin