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CompletedNCT03400475Updated Dec 19, 2018Results posted

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

A Phase 2 interventional study of Simvastatin and Placebo in Peri-implant Mucositis, sponsored by Ahmed Mohamed Mahrous. Completed at 1 site in United States. Open to participants aged 18 Years to 80 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-12-19.

Sponsored by Ahmed Mohamed Mahrous · Phase 2, Interventional, and Treatment

From the registry’s dates

  • Registered 2 years 8 months after the study started (first participant enrolled Apr 2015, registered Jan 2018).
Phase
Phase 2
Study type
Interventional
Enrollment
46
Allocation
Randomized
Ages
18 Years to 80 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Peri-implant Mucositis

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Keywords

  • topical
  • subgingival
  • simvastatin
03

In context

Mucositis

265 studies on the registry are indexed under Mucositis; 34 are open to participants now.

This study's enrollment of 46 is close to the median of 45 across 215 interventional studies indexed under Mucositis.

Browse Mucositis studies →

Lead sponsor

This is the only study on the registry with Ahmed Mohamed Mahrous as lead sponsor.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Read, understand, and sign the 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

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, medications or immunosuppressed patients
  • Have paraben allergies
  • Have soybean allergies
Terms in these criteria, in plain language(2)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
46 participants (actual)

Study arms

  • Experimental
    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.

    Drug: Simvastatin

  • Placebo comparator
    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.

    Other: Placebo

Interventions

  • DrugSimvastatin

    One topical application in peri-implant gingival crevice

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

  • OtherPlacebo

    One topical application in peri-implant gingival crevice

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

06

What researchers measure

Primary outcomes

  1. 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)

    Time frame: Baseline- 24hrs

  2. 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)

    Time frame: Baseline - 1 week

  3. 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)

    Time frame: 24 hours - 1 week

  4. 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)

    Time frame: Baseline - 24 hours

  5. 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)

    Time frame: Baseline - 1 week

  6. 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)

    Time frame: 24 hours - 1 week

  7. 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)

    Time frame: Baseline - 24 hours

  8. 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)

    Time frame: Baseline - 1 week

  9. 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)

    Time frame: 24 hours - 1 week

  10. 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)

    Time frame: Baseline- 24hrs

  11. 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)

    Time frame: Baseline - 1 week

  12. 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)

    Time frame: 24hrs - 1 week

Secondary outcomes

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

    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 are summed together and divided by 4 to reach an overall score.

    Time frame: Baseline

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

    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 are summed together and divided by 4 to reach an overall score.

    Time frame: 24 hours

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

    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 are summed together and divided by 4 to reach an overall score.

    Time frame: 1 week

  4. Probing Depth Level (Averaged Over 6 Sites) at Baseline

    Depth will be measured by a calibrated periodontal probe at 6 different locations, Mesiobuccal, Mid Buccal, Distobuccal, Disto Lingual, Mid Lingual and Mesio Lingual. The longitudinal course will be characterized with respect to the categorical outcome, presence of any bleeding on probing, with initial emphasis being placed upon transition approaches, with specific attention given to shifts from clinically unacceptable to clinically acceptable designations. probing depth is considered variable from one person to the other however a decrease or a shallower probing depth overtime is gererally seen as an improvement , thus any decrease in probing depth would be seen as signs of healing.

    Time frame: Baseline

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

    Depth will be measured by a calibrated periodontal probe at 6 different locations, Mesiobuccal, Mid Buccal, Distobuccal, Disto Lingual, Mid Lingual and Mesio Lingual. The longitudinal course will be characterized with respect to the categorical outcome, presence of any bleeding on probing, with initial emphasis being placed upon transition approaches, with specific attention given to shifts from clinically unacceptable to clinically acceptable designations. probing depth is considered variable from one person to the other however a decrease or a shallower probing depth overtime is gererally seen as an improvement , thus any decrease in probing depth would be seen as signs of healing.

    Time frame: 24 hours

  6. Probing Depth Level (Averaged Over 6 Sites) at 1 Week

    Depth will be measured by a calibrated periodontal probe at 6 different locations, Mesiobuccal, Mid Buccal, Distobuccal, Disto Lingual, Mid Lingual and Mesio Lingual. The longitudinal course will be characterized with respect to the categorical outcome, presence of any bleeding on probing, with initial emphasis being placed upon transition approaches, with specific attention given to shifts from clinically unacceptable to clinically acceptable designations. probing depth is considered variable from one person to the other however a decrease or a shallower probing depth overtime is gererally seen as an improvement , thus any decrease in probing depth would be seen as signs of healing.

    Time frame: 1 week

07

Results

Posted Nov 29, 2018

Participant flow

Participant flow — Overall Study
MilestoneTest GroupControl Group
Started2422
Completed2422
Not completed00

Outcome measures

PrimaryChange 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)

Time frame:
Baseline- 24hrs
Reported as:
Mean · Micrograms per deciliter (ug/dl)
Change in Interleukin 1 B at Base to 24 Hours
Micrograms per deciliter (ug/dl)Simvastatin Group ( Treatment )Control Group
Change in Interleukin 1 B at Base to 24 Hours-1.075 ± 15.5871.013 ± 5.273
Statistical analysis
  • Simvastatin Group ( Treatment ) vs Control Group · Wilcoxon (Mann-Whitney) · p = 0.90 · Mean difference (final values): -2.088
PrimaryChange 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)

Time frame:
Baseline - 1 week
Reported as:
Mean · Micrograms per deciliter (ug/dl)
Change in Interleukin 1 B at Base to 1 Week
Micrograms per deciliter (ug/dl)Simvastatin Group ( Treatment )Control Group
Change in Interleukin 1 B at Base to 1 Week2.5016 ± 15.4701-1.095 ± 8.6050
Statistical analysis
  • Simvastatin Group ( Treatment ) vs Control Group · Wilcoxon (Mann-Whitney) · p = 0.90 · Mean difference (final values): 3.59
PrimaryChange 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)

Time frame:
24 hours - 1 week
Reported as:
Mean · Micrograms per deciliter (ug/dl)
Change in Interleukin 1 B 24 Hours - 1 Week
Micrograms per deciliter (ug/dl)Simvastatin Group ( Treatment )Control Group
Change in Interleukin 1 B 24 Hours - 1 Week3.577 ± 14.137-2.108 ± 10.569
Statistical analysis
  • Simvastatin Group ( Treatment ) vs Control Group · Wilcoxon (Mann-Whitney) · p = 0.90 · Mean difference (final values): 3.596
PrimaryChange 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)

Time frame:
Baseline - 24 hours
Reported as:
Mean · Micrograms per deciliter (ug/dl)
Change in Interleukin 6 at Base to 24 Hours
Micrograms per deciliter (ug/dl)Simvastatin Group ( Treatment )Control Group
Change in Interleukin 6 at Base to 24 Hours0.118 ± 0.9540.201 ± 0.880
Statistical analysis
  • Simvastatin Group ( Treatment ) vs Control Group · Wilcoxon (Mann-Whitney) · p = 0.90 · Mean difference (final values): -0.083
PrimaryChange 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)

Time frame:
Baseline - 1 week
Reported as:
Mean · Micrograms per deciliter (ug/dl)
Change in Interleukin 6 Baseline to 1 Week
Micrograms per deciliter (ug/dl)Simvastatin Group ( Treatment )Control Group
Change in Interleukin 6 Baseline to 1 Week0.304 ± 1.37440.275 ± 1.296
Statistical analysis
  • Simvastatin Group ( Treatment ) vs Control Group · Wilcoxon (Mann-Whitney) · p = 0.90 · Mean difference (final values): 0.581
PrimaryChange 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)

Time frame:
24 hours - 1 week
Reported as:
Mean · Micrograms per deciliter (ug/dl)
Change in Interleukin 6 24 Hours - 1 Week
Micrograms per deciliter (ug/dl)Simvastatin Group ( Treatment )Control Group
Change in Interleukin 6 24 Hours - 1 Week0.185 ± 2.0390.073 ± 1.522
Statistical analysis
  • Simvastatin Group ( Treatment ) vs Control Group · Wilcoxon (Mann-Whitney) · p = 0.90 · Mean difference (final values): 0.029
PrimaryChange 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)

Time frame:
Baseline - 24 hours
Reported as:
Mean · Micrograms per deciliter (ug/dl)
Change in Interleukin 8 at Base to 24 Hours
Micrograms per deciliter (ug/dl)Simvastatin Group ( Treatment )Control Group
Change in Interleukin 8 at Base to 24 Hours0.00 ± 331.02164.696 ± 197.902
Statistical analysis
  • Simvastatin Group ( Treatment ) vs Control Group · Wilcoxon (Mann-Whitney) · p = 0.86 · Mean difference (final values): -64.696
PrimaryChange 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)

Time frame:
Baseline - 1 week
Reported as:
Mean · Micrograms per deciliter (ug/dl)
Change in Interleukin 8 at Base to 1 Week
Micrograms per deciliter (ug/dl)Simvastatin Group ( Treatment )Control Group
Change in Interleukin 8 at Base to 1 Week131.368 ± 480.83520.275 ± 389.666
Statistical analysis
  • Simvastatin Group ( Treatment ) vs Control Group · Wilcoxon (Mann-Whitney) · p = 0.86 · Mean difference (final values): 111.03
PrimaryChange 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)

Time frame:
24 hours - 1 week
Reported as:
Mean · Micrograms per deciliter (ug/dl)
Change in Interleukin 8 24 Hours to 1 Week
Micrograms per deciliter (ug/dl)Simvastatin Group ( Treatment )Control Group
Change in Interleukin 8 24 Hours to 1 Week168.894 ± 548.154-44.42 ± 484.019
Statistical analysis
  • Simvastatin Group ( Treatment ) vs Control Group · Wilcoxon (Mann-Whitney) · p = 0.86 · Mean difference (final values): 213.314
PrimaryChange 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)

Time frame:
Baseline- 24hrs
Reported as:
Mean · Micrograms per deciliter (ug/dl)
Change in Tumor Necrosis Factor Alpha at Base to 24 Hours
Micrograms per deciliter (ug/dl)Simvastatin Group ( Treatment )Control Group
Change in Tumor Necrosis Factor Alpha at Base to 24 Hours37.526 ± 1.266-0.17 ± 1.589
Statistical analysis
  • Simvastatin Group ( Treatment ) vs Control Group · Wilcoxon (Mann-Whitney) · p = 0.41 · Mean difference (final values): 37.356
PrimaryChange 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)

Time frame:
Baseline - 1 week
Reported as:
Mean · Micrograms per deciliter (ug/dl)
Change in Tumor Necrosis Factor Alpha at Base to 1 Week
Micrograms per deciliter (ug/dl)Simvastatin Group ( Treatment )Control Group
Change in Tumor Necrosis Factor Alpha at Base to 1 Week1.5833 ± 5.665-0.0704 ± 2.8536401
Statistical analysis
  • Simvastatin Group ( Treatment ) vs Control Group · Wilcoxon (Mann-Whitney) · p = 0.41 · Mean difference (final values): 1.6537
PrimaryChange 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)

Time frame:
24hrs - 1 week
Reported as:
Mean · Micrograms per deciliter (ug/dl)
Change in Tumor Necrosis Factor Alpha 24 Hours to 1 Week
Micrograms per deciliter (ug/dl)Simvastatin Group ( Treatment )Control Group
Change in Tumor Necrosis Factor Alpha 24 Hours to 1 Week1.641 ± 5.72170.095 ± 3.633
Statistical analysis
  • Simvastatin Group ( Treatment ) vs Control Group · Wilcoxon (Mann-Whitney) · p = 0.41 · Mean difference (final values): 1.552
SecondaryGingival Index Level (Derived From an Average Over the 4 Implant Sites) at Baseline

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 are summed together and divided by 4 to reach an overall score.

Time frame:
Baseline
Reported as:
Number · participants
Gingival Index Level (Derived From an Average Over the 4 Implant Sites) at Baseline
participantsSimvastatin Group ( Treatment)Control Group
Gingival index score of 0.5010
Gingival index score of 100
Gingival index score of 1.251812
Gingival index score of 1.548
Gingival index score of 1.7512
Statistical analysis
  • Simvastatin Group ( Treatment) vs Control Group · Fisher Exact · p = 0.071
SecondaryGingival Index Level (Derived From an Average Over the 4 Implant Sites) at 24 Hours

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 are summed together and divided by 4 to reach an overall score.

Time frame:
24 hours
Reported as:
Number · participants
Gingival Index Level (Derived From an Average Over the 4 Implant Sites) at 24 Hours
participantsSimvastatin Group ( Treatment)Control Group
Gingival sscore of 0.5011
Gingival sscore of 1164
Gingival sscore of 1.25612
Gingival sscore of 1.5015
Gingival sscore of 1.7500
Statistical analysis
  • Simvastatin Group ( Treatment) vs Control Group · Fisher Exact · p = 0.071
SecondaryGingival Index Level (Derived From an Average Over the 4 Implant Sites) at 1 Week

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 are summed together and divided by 4 to reach an overall score.

Time frame:
1 week
Reported as:
Number · participants
Gingival Index Level (Derived From an Average Over the 4 Implant Sites) at 1 Week
participantsSimvastatin Group ( Treatment)Control Group
Gingival sscore of 0.5011
Gingival sscore of 121
Gingival sscore of 1.251717
Gingival sscore of 1.5043
Gingival sscore of 1.7500
Statistical analysis
  • Simvastatin Group ( Treatment) vs Control Group · Fisher Exact · p = 1
SecondaryProbing Depth Level (Averaged Over 6 Sites) at Baseline

Depth will be measured by a calibrated periodontal probe at 6 different locations, Mesiobuccal, Mid Buccal, Distobuccal, Disto Lingual, Mid Lingual and Mesio Lingual. The longitudinal course will be characterized with respect to the categorical outcome, presence of any bleeding on probing, with initial emphasis being placed upon transition approaches, with specific attention given to shifts from clinically unacceptable to clinically acceptable designations. probing depth is considered variable from one person to the other however a decrease or a shallower probing depth overtime is gererally seen as an improvement , thus any decrease in probing depth would be seen as signs of healing.

Time frame:
Baseline
Reported as:
Number · participants
Probing Depth Level (Averaged Over 6 Sites) at Baseline
participantsSimvastatin Group ( Treatment)Control Group
Probing Depth Score 101
Probing Depth Score 235
Probing Depth 3910
Probing Depth 496
Probing Depth 530
Probing Depth 600
Statistical analysis
  • Simvastatin Group ( Treatment) vs Control Group · Fisher Exact · p = 0.062
SecondaryProbing Depth Level (Averaged Over 6 Sites) at 24 Hours

Depth will be measured by a calibrated periodontal probe at 6 different locations, Mesiobuccal, Mid Buccal, Distobuccal, Disto Lingual, Mid Lingual and Mesio Lingual. The longitudinal course will be characterized with respect to the categorical outcome, presence of any bleeding on probing, with initial emphasis being placed upon transition approaches, with specific attention given to shifts from clinically unacceptable to clinically acceptable designations. probing depth is considered variable from one person to the other however a decrease or a shallower probing depth overtime is gererally seen as an improvement , thus any decrease in probing depth would be seen as signs of healing.

Time frame:
24 hours
Reported as:
Number · participants
Probing Depth Level (Averaged Over 6 Sites) at 24 Hours
participantsSimvastatin Group ( Treatment)Control Group
Probing Depth Score 110
Probing Depth Score 255
Probing Depth 3710
Probing Depth 486
Probing Depth 521
Probing Depth 610
Statistical analysis
  • Simvastatin Group ( Treatment) vs Control Group · Fisher Exact · p = 0.54
SecondaryProbing Depth Level (Averaged Over 6 Sites) at 1 Week

Depth will be measured by a calibrated periodontal probe at 6 different locations, Mesiobuccal, Mid Buccal, Distobuccal, Disto Lingual, Mid Lingual and Mesio Lingual. The longitudinal course will be characterized with respect to the categorical outcome, presence of any bleeding on probing, with initial emphasis being placed upon transition approaches, with specific attention given to shifts from clinically unacceptable to clinically acceptable designations. probing depth is considered variable from one person to the other however a decrease or a shallower probing depth overtime is gererally seen as an improvement , thus any decrease in probing depth would be seen as signs of healing.

Time frame:
1 week
Reported as:
Number · participants
Probing Depth Level (Averaged Over 6 Sites) at 1 Week
participantsSimvastatin Group ( Treatment)Control Group
Probing Depth Score 110
Probing Depth Score 244
Probing Depth 3813
Probing Depth 473
Probing Depth 542
Probing Depth 600
Statistical analysis
  • Simvastatin Group ( Treatment) vs Control Group · Fisher Exact · p = 0.34

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Test Group—0/24 (0%)0/24 (0%)
Control Group—0/22 (0%)0/22 (0%)

Baseline characteristics

each patient is considered one unit

Age, Continuous
Age, Continuous(years)Test GroupControl GroupTotal
Mean63.45 ± 13.363.1 ± 14.363.3 ± 13.7
Sex: Female, Male
Sex: Female, Male(Participants)Test GroupControl GroupTotal
Female171330
Male7916
Region of Enrollment
Region of Enrollment(participants)Test GroupControl GroupTotal
United States242246
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Study locations

1 site
  • University of Iowa College of Dentistry and Dental Clinics
    Iowa City, Iowa 52242, United States
09

References and documents

Publications

  • 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. PubMed 20151799 ↗
  • 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. PubMed 16955604 ↗
  • 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. PubMed 16642902 ↗
  • 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. PubMed 16723648 ↗
  • 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. PubMed 22592038 ↗
  • 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. PubMed 19302394 ↗
  • 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. PubMed 10933353 ↗

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 19, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03400475
Lead sponsor
Ahmed Mohamed Mahrous
Collaborators
Greater New York Academy of Prosthodontics, American College of Prosthodontists Education Foundation, University of Iowa
Responsible party
Ahmed Mohamed Mahrous (Clinical Assistant Professor, University of Iowa) — Sponsor-investigator
First posted
Jan 17, 2018
Start date
Apr 23, 2015
Primary completion
Oct 24, 2016
Completion
Oct 24, 2016
Results posted
Nov 29, 2018
Last update
Dec 19, 2018

Study contacts

Ahmed M Mahrous, B.D.S., M.S.
principal investigator · University of Iowa College of Dentistry and Dental Clinics

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Nov 2018. You cannot join it, but the record below documents what was studied.

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