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

NCT03400475 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 201410714
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

Peri-implant Mucositis

Keywords

topical; subgingival; simvastatin

Outcome Measures

Primary Outcomes (12)

• Change in Interleukin 1 B at Base to 24 Hours

  Measuring the change in Cytokine levels in the peri implant crevicular fluid ( Fluid around the implant) by extracting the fluid and measuring the levels of the interlukins in the fluids in Micrograms per dicileter ( ug/dl)

  Baseline- 24hrs

• Change in Interleukin 1 B at Base to 1 Week

  Measuring the change in Cytokine levels in the peri implant crevicular fluid ( Fluid around the implant) by extracting the fluid and measuring the levels of the interlukins in the fluids in Micrograms per dicileter ( ug/dl)

  Baseline - 1 week

• Change in Interleukin 1 B 24 Hours - 1 Week

  Measuring the change in Cytokine levels in the peri implant crevicular fluid ( Fluid around the implant) by extracting the fluid and measuring the levels of the interlukins in the fluids in Micrograms per dicileter ( ug/dl)

  24 hours - 1 week

• Change in Interleukin 6 at Base to 24 Hours

  Measuring the change in Cytokine levels in the peri implant crevicular fluid ( Fluid around the implant) by extracting the fluid and measuring the levels of the interlukins in the fluids in Micrograms per dicileter ( ug/dl)

  Baseline - 24 hours

• Change in Interleukin 6 Baseline to 1 Week

  Measuring the change in Cytokine levels in the peri implant crevicular fluid ( Fluid around the implant) by extracting the fluid and measuring the levels of the interlukins in the fluids in Micrograms per dicileter ( ug/dl)

  Baseline - 1 week

• Change in Interleukin 6 24 Hours - 1 Week

  Measuring the change in Cytokine levels in the peri implant crevicular fluid ( Fluid around the implant) by extracting the fluid and measuring the levels of the interlukins in the fluids in Micrograms per dicileter ( ug/dl)

  24 hours - 1 week

• Change in Interleukin 8 at Base to 24 Hours

  Measuring the change in Cytokine levels in the peri implant crevicular fluid ( Fluid around the implant) by extracting the fluid and measuring the levels of the interlukins in the fluids in Micrograms per dicileter ( ug/dl)

  Baseline - 24 hours

• Change in Interleukin 8 at Base to 1 Week

  Measuring the change in Cytokine levels in the peri implant crevicular fluid ( Fluid around the implant) by extracting the fluid and measuring the levels of the interlukins in the fluids in Micrograms per dicileter ( ug/dl)

  Baseline - 1 week

• Change in Interleukin 8 24 Hours to 1 Week

  Measuring the change in Cytokine levels in the peri implant crevicular fluid ( Fluid around the implant) by extracting the fluid and measuring the levels of the interlukins in the fluids in Micrograms per dicileter ( ug/dl)

  24 hours - 1 week

• Change in Tumor Necrosis Factor Alpha at Base to 24 Hours

  Measuring the change in Cytokine levels in the peri implant crevicular fluid ( Fluid around the implant) by extracting the fluid and measuring the levels of the interlukins in the fluids in Micrograms per dicileter ( ug/dl)

  Baseline- 24hrs

• Change in Tumor Necrosis Factor Alpha at Base to 1 Week

  Measuring the change in Cytokine levels in the peri implant crevicular fluid ( Fluid around the implant) by extracting the fluid and measuring the levels of the interlukins in the fluids in Micrograms per dicileter ( ug/dl)

  Baseline - 1 week

• Change in Tumor Necrosis Factor Alpha 24 Hours to 1 Week

  Measuring the change in Cytokine levels in the peri implant crevicular fluid ( Fluid around the implant) by extracting the fluid and measuring the levels of the interlukins in the fluids in Micrograms per dicileter ( ug/dl)

  24hrs - 1 week

Secondary Outcomes (6)

• Gingival Index Level (Derived From an Average Over the 4 Implant Sites) at Baseline

  Baseline

• Gingival Index Level (Derived From an Average Over the 4 Implant Sites) at 24 Hours

  24 hours

• Gingival Index Level (Derived From an Average Over the 4 Implant Sites) at 1 Week

  1 week

• Probing Depth Level (Averaged Over 6 Sites) at Baseline

  Baseline

• Probing Depth Level (Averaged Over 6 Sites) at 24 Hours

  24 hours

Study Arms (2)

Simvastatin group (Treatment)

EXPERIMENTAL

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.

Drug: Simvastatin

Control group

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

Simvastatin DRUG

One topical application in peri-implant gingival crevice

Also known as: Simvastatin Powder U.S.P.

Simvastatin group (Treatment)

Placebo OTHER

One topical application in peri-implant gingival crevice

Also known as: Lecithin/isopropyl palmitate solution, Poloxamer 407 gel, Lipoil®, Polox Gel 20%®

Control group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ahmed Mohamed Mahrous: lead
• Greater New York Academy of Prosthodontics: collaborator
• American College of Prosthodontists Education Foundation: collaborator
• University of Iowa: collaborator

Study Sites (1)

University of Iowa College of Dentistry and Dental Clinics

Iowa City, Iowa, 52242, United States

Location

Related Publications (7)

• 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.

  PMID: 20151799 BACKGROUND

• 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.

  PMID: 16955604 BACKGROUND

• 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.

  PMID: 16642902 BACKGROUND

• 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.

  PMID: 16723648 BACKGROUND

• 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.

  PMID: 22592038 BACKGROUND

• 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.

  PMID: 19302394 BACKGROUND

• 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.

  PMID: 10933353 BACKGROUND

MeSH Terms

Interventions

Simvastatin; Lecithins

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Phosphatidylcholines; Glycerophospholipids; Phosphatidic Acids; Glycerophosphates; Phospholipids; Membrane Lipids; Lipids; Plant Extracts; Plant Preparations; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Dr. Ahmed Mahrous
• Organization: University of Iowa

ahmedmohamed-mahrous@uiowa.edu

3193336517

Study Officials

• Ahmed M Mahrous, B.D.S., M.S.

  University of Iowa College of Dentistry and Dental Clinics

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Only the study coordinator will know whether the intervention is simvastatin or control.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: January 2, 2018
• First Posted: January 17, 2018
• Study Start: April 23, 2015
• Primary Completion: October 24, 2016
• Study Completion: October 24, 2016
• Last Updated: December 19, 2018
• Results First Posted: November 29, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)