Use of Topical Subgingival Application of Simvastatin Gel in the Treatment of Peri-Implant Mucositis

NCT ID: NCT03400475

Last Updated: 2018-12-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-23
• Study Completion Date: 2016-10-24

Brief 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.

Conditions

Peri-implant Mucositis

Keywords

topical; subgingival; simvastatin

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Simvastatin group (Treatment)

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.

Group Type: EXPERIMENTAL

Simvastatin

Intervention Type: DRUG

One topical application in peri-implant gingival crevice

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

One topical application in peri-implant gingival crevice

Interventions

Simvastatin

One topical application in peri-implant gingival crevice

Intervention Type: DRUG

Placebo

One topical application in peri-implant gingival crevice

Intervention Type: OTHER

Other Intervention Names

Simvastatin Powder U.S.P.; Lecithin/isopropyl palmitate solution, Poloxamer 407 gel; Lipoil®, Polox Gel 20%®

Eligibility Criteria

Inclusion Criteria

• Read, understand, and sign the informed consent forms
• Have at least 1 dental implant
• Have no evidence of peri-implantitis as evidenced by mesial and distal bone loss more than 1 mm from the accepted reference point round the implants on the periapical radiograph
• Demonstrate peri-implant mucositis as evidenced by bleeding on probing with 0.25 N/cm

Exclusion Criteria

• Have allergic reactions to simvastatin
• Have peri-implantitis as evidenced by more than 1 mm of mesial and distal bone loss from an accepted reference point on the implants on the periapical radiograph
• Demonstrate no bleeding on probing with 0.25 N/ cm
• Have uncontrolled systemic disease
• Pregnancy or females who suspect/may be pregnant, as well as nursing and breast feeding mothers
• Take statin / HMG-CoA reductase inhibitor medications
• Smokers
• Require antibiotic prophylaxis
• Take anti-inflammatory medication, immunosuppressive medications or immunosuppressed patients
• Have paraben allergies
• Have soybean allergies

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Greater New York Academy of Prosthodontics

UNKNOWN

Sponsor Role: collaborator

American College of Prosthodontists Education Foundation

UNKNOWN

Sponsor Role: collaborator

University of Iowa

OTHER

Sponsor Role: collaborator

Ahmed Mohamed Mahrous

OTHER

Sponsor Role: lead

Responsible Party

Ahmed Mohamed Mahrous

Clinical Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ahmed M Mahrous, B.D.S., M.S.

Role: PRINCIPAL_INVESTIGATOR

University of Iowa College of Dentistry and Dental Clinics

Locations

University of Iowa College of Dentistry and Dental Clinics

Iowa City, Iowa, United States

Countries

United States

References

Pradeep AR, Thorat MS. Clinical effect of subgingivally delivered simvastatin in the treatment of patients with chronic periodontitis: a randomized clinical trial. J Periodontol. 2010 Feb;81(2):214-22. doi: 10.1902/jop.2009.090429.

Reference Type: BACKGROUND

PMID: 20151799 (View on PubMed)

Liskmann S, Vihalemm T, Salum O, Zilmer K, Fischer K, Zilmer M. Correlations between clinical parameters and interleukin-6 and interleukin-10 levels in saliva from totally edentulous patients with peri-implant disease. Int J Oral Maxillofac Implants. 2006 Jul-Aug;21(4):543-50.

Reference Type: BACKGROUND

PMID: 16955604 (View on PubMed)

Konttinen YT, Lappalainen R, Laine P, Kitti U, Santavirta S, Teronen O. Immunohistochemical evaluation of inflammatory mediators in failing implants. Int J Periodontics Restorative Dent. 2006 Apr;26(2):135-41.

Reference Type: BACKGROUND

PMID: 16642902 (View on PubMed)

Sakoda K, Yamamoto M, Negishi Y, Liao JK, Node K, Izumi Y. Simvastatin decreases IL-6 and IL-8 production in epithelial cells. J Dent Res. 2006 Jun;85(6):520-3. doi: 10.1177/154405910608500608.

Reference Type: BACKGROUND

PMID: 16723648 (View on PubMed)

Guncu GN, Akman AC, Gunday S, Yamalik N, Berker E. Effect of inflammation on cytokine levels and bone remodelling markers in peri-implant sulcus fluid: a preliminary report. Cytokine. 2012 Aug;59(2):313-6. doi: 10.1016/j.cyto.2012.04.024. Epub 2012 May 14.

Reference Type: BACKGROUND

PMID: 22592038 (View on PubMed)

Duarte PM, de Mendonca AC, Maximo MB, Santos VR, Bastos MF, Nociti Junior FH. Differential cytokine expressions affect the severity of peri-implant disease. Clin Oral Implants Res. 2009 May;20(5):514-20. doi: 10.1111/j.1600-0501.2008.01680.x. Epub 2009 Mar 11.

Reference Type: BACKGROUND

PMID: 19302394 (View on PubMed)

Ferro D, Parrotto S, Basili S, Alessandri C, Violi F. Simvastatin inhibits the monocyte expression of proinflammatory cytokines in patients with hypercholesterolemia. J Am Coll Cardiol. 2000 Aug;36(2):427-31. doi: 10.1016/s0735-1097(00)00771-3.

Reference Type: BACKGROUND

PMID: 10933353 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

201410714

Identifier Type: -

Identifier Source: org_study_id