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Antiseptic Effects on the Dental Implant Internal Surface Microbiome

Primary Purpose

Peri-Implantitis, Peri-implant Mucositis, Implant Infection

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Chlorhexidine
Hydrogen Peroxide
Sponsored by
Madigan Army Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peri-Implantitis

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Active duty military
  • 18-55 years old
  • Over 6 months remaining at local duty station

Exclusion Criteria:

  • Tobacco user
  • Medications that affect soft tissue or bone healing
  • Metabolic disorder that affects soft tissue or bone healing
  • Active periodontal disease

Sites / Locations

  • Madigan Army Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

No Intervention

Experimental

Experimental

Arm Label

Control

Chlorhexidine

Hydrogen Peroxide

Arm Description

This arm will receive standard of care during dental implant insertion.

Chlorhexidine treatment.

Hydrogen Peroxide treatment.

Outcomes

Primary Outcome Measures

Implant Failure
We will compare the rates of dental implant failure between study arms.

Secondary Outcome Measures

Peri-Implantitis
We will compare the rates of peri-implantitis between study arms.
Bacterial Load
We will compare the bacterial load in the dental implant internal cavity between study arms.
Microbiome Composition
We will compare the relative abundance of red and orange complex bacteria in the dental implant internal cavity between study arms.

Full Information

First Posted
August 23, 2021
Last Updated
January 19, 2023
Sponsor
Madigan Army Medical Center
Collaborators
United States Department of Defense
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1. Study Identification

Unique Protocol Identification Number
NCT05024760
Brief Title
Antiseptic Effects on the Dental Implant Internal Surface Microbiome
Official Title
Antiseptic Effects on the Dental Implant Internal Surface Microbiome
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 28, 2022 (Actual)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
April 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Madigan Army Medical Center
Collaborators
United States Department of Defense

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
Soldiers operate in environments that are more likely to lead to oral trauma, risking poor dentition which can directly impact military readiness. Dental restoration can often be accomplished via dental implant insertion. Microbiome-associated complications that result in bone loss, including the micro-leakage of bacterial species proliferating in the dental implant internal cavity, frequently lead to implant failure. Reduction in implant bacterial load may result in a shift of the composition of the microbiome in favor of less pathogenic species, potentially improving dental implant success rates, reducing surgical revisions, and associated cost savings. This study aims to determine how disinfectant gel (hydrogen peroxide or chlorhexidine) insertion into dental implant internal cavities affects implant failure rates, bacterial load and microbiome composition.
Detailed Description
Clinical Background Peri-implantitis/mucositis is bone loss/tissue inflammation around a dental implant. This is caused by bacterial biofilm at the interface between the implant and bone/tissue. The source of bacteria comes from the internal surface of the implant, and leaks through the implant/abutment interface. After the dental implant is placed in bone, bacteria from the saliva and blood within the internal surface of the implant leak out. The body reacts to this bacterial exposure with inflammation, resulting in bone loss around the implant/abutment interface. Warfighters are exposed to situations in which the risk of dental trauma is elevated compared with the civilian population. This is particularly problematic for the military because poor dentition can disqualify Soldiers from service. Proper mastication is crucial to readiness. The number of implants inserted annually has risen by more than 10-fold since the 1980s. There are now over 700,000 implants inserted annually (Battle-Siatita et al., 2009). Unfortunately, implant-associated infections such as peri-implant mucositis and peri-implantitis are common, affecting approximately 63% and 19% of recipients, respectively (Atieh et al., 2013). Though, it should be noted that others have suggested the number could be as high as 80% (Podhorsky et al., 2016). Because these conditions negatively impact implant success rates, preventive measures aimed at reducing the risk of these diseases have tremendous potential to transform dental care and improve readiness. Previous studies have found evidence suggesting that microbial profiles differ between healthy implants and those exhibiting peri-implantitis (Schwarz et al., 2018). For example, at least 19 species such as Porphyromonas gingivalis, Pseudomonas aeruginosa, and Staphylococcus aureus are more abundant on affected implants (Schwarz et al., 2018). Thus, it may be important to not only control total bacterial load but also to ensure that any intervention produces a favorable change in the implant-associated microbial profile. A recent systematic review determined that there is strong evidence to support the use of chlorhexidine rinses after implant surgery (Solderer et al., 2019). The positive effects of chlorhexidine rinses on implant success appear to be the result of the impact of chlorhexidine on reducing biofilm-related complications (Daubert & Weinstein, 2019; Solderer et al., 2019). While the effects of chlorhexidine rinses have been well described, there has been little investigation into the potential impact of disinfectants placed within the internal cavity of dental implants. A PubMed search for "dental implant internal disinfectant" returned only 15 articles in English. Of the articles considering the implant's internal cavity, 4 were in vitro studies (Besimo et al., 1999; Duarte et al., 2006; Podhorsky, Biscoping, et al., 2016; Podhorsky, Putzier, et al., 2016). All 4 studies strongly support the use of chlorhexidine gel in the internal cavity of implants. Another 4 studies, examined the ability of chlorhexidine gel placed within the dental implant internal cavity to affect total bacterial load between 3 and 6 months after surgery (Carinci et al., 2019; D'Ercole et al., 2009; Ghannad et al., 2015; Paolantonio et al., 2008). All 4 studies reported that intervention resulted in decreased bacterial load. Using PCR specific to only 6 bacterial taxa or using culturing methods, two of these manuscripts reported no change in microbial profiles (Ghannad et al., 2015; Paolantonio et al., 2008). However, one paper reported that the gel altered microbial profiles (D'Ercole et al., 2009). Given that the oral microbiome consists of hundreds of bacterial species, these previous studies have inadequately examined the impact of chlorhexidine gel on microbial profiles. Moreover, there have been no studies examining the use of alternative disinfectants. Another common disinfectant used intraorally is hydrogen peroxide. This disinfectant is used to treat periodontitis and for teeth whitening. We propose to analyze the effect of this second material on total bacterial load and the microbial profile within the internal aspect of the dental implant. The rate and degree of peri-implantitis/mucositis, bone/tissue loss, and inflammation, coupled with the determination of bacterial load and microbiome composition will allow for the determination of the value of hydrogen peroxide or chlorhexidine placed within the dental implant internal cavity. Problem/Question Certain bacteria from the saliva and blood that get inside the implant are more pathogenic (disease causing) than others. In the dental field, there are topcial agents regularly used as mouth rinses to decrease this bacterial load, and create a healthier bacterial environment with less pathogenic potential. Because of the nature of the job, warfighters are at increased risk of oral trauma compared with the civilian population. Corrective procedures following trauma often include the insertion of dental implants. The number of annual dental implant insertions has risen more than 10-fold since the 1980s, and now sits at more than 700,000 per year (Battle-Siatita et al., 2009). Unfortunately, dental implant failure rates are high. This has high costs because of the need for additional surgeries, reduced quality of care, and reduced warfighter readiness. The implant-associated microbiome has been implicated as a key effector in implant failure and bone loss. In this study, we aim to evaluate methods that reduce or alter the implant-associated microbiome and therefore improve implant success rates.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peri-Implantitis, Peri-implant Mucositis, Implant Infection, Dental Implant Failed

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Model Description
This is a 3 arm study with 1 arm receiving no treatment and 2 arms receiving treatments.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Control
Arm Type
No Intervention
Arm Description
This arm will receive standard of care during dental implant insertion.
Arm Title
Chlorhexidine
Arm Type
Experimental
Arm Description
Chlorhexidine treatment.
Arm Title
Hydrogen Peroxide
Arm Type
Experimental
Arm Description
Hydrogen Peroxide treatment.
Intervention Type
Drug
Intervention Name(s)
Chlorhexidine
Intervention Description
Chlorhexidine will be inserted into the dental implant internal cavity during dental implant insertion.
Intervention Type
Drug
Intervention Name(s)
Hydrogen Peroxide
Intervention Description
Hydrogen Peroxide will be inserted into the internal cavity of the dental implant during dental implant insertion.
Primary Outcome Measure Information:
Title
Implant Failure
Description
We will compare the rates of dental implant failure between study arms.
Time Frame
Four months post dental implant insertion.
Secondary Outcome Measure Information:
Title
Peri-Implantitis
Description
We will compare the rates of peri-implantitis between study arms.
Time Frame
Four months post dental implant insertion.
Title
Bacterial Load
Description
We will compare the bacterial load in the dental implant internal cavity between study arms.
Time Frame
Four months post dental implant insertion.
Title
Microbiome Composition
Description
We will compare the relative abundance of red and orange complex bacteria in the dental implant internal cavity between study arms.
Time Frame
Four months post dental implant insertion.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Active duty military 18-55 years old Over 6 months remaining at local duty station Exclusion Criteria: Tobacco user Medications that affect soft tissue or bone healing Metabolic disorder that affects soft tissue or bone healing Active periodontal disease
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kevin D Smith, DMD
Phone
253-968-0181
Email
kevin.d.smith2.mil@health.mil
First Name & Middle Initial & Last Name or Official Title & Degree
Zachary T Colburn, PhD
Phone
253-968-3455
Email
zachary.t.colburn.civ@health.mil
Facility Information:
Facility Name
Madigan Army Medical Center
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98431
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kevin Smith
Phone
253-968-0181
Email
kevin.d.smith2.mil@health.mil

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
19485117
Citation
Battle-Siatita SO, Bartoloni JA, Hancock RH, Chong CH. Retrospective analysis of dental implants among United States Air Force basic military trainees. Mil Med. 2009 Apr;174(4):437-40. doi: 10.7205/milmed-d-02-5008.
Results Reference
background
PubMed Identifier
23237585
Citation
Atieh MA, Alsabeeha NH, Faggion CM Jr, Duncan WJ. The frequency of peri-implant diseases: a systematic review and meta-analysis. J Periodontol. 2013 Nov;84(11):1586-98. doi: 10.1902/jop.2012.120592. Epub 2012 Dec 13.
Results Reference
background
PubMed Identifier
27183065
Citation
Podhorsky A, Biscoping S, Rehmann P, Streckbein P, Domann E, Wostmann B. Transfer of Bacteria into the Internal Cavity of Dental Implants After Application of Disinfectant or Sealant Agents In Vitro. Int J Oral Maxillofac Implants. 2016 May-Jun;31(3):563-70. doi: 10.11607/jomi.4408.
Results Reference
background
PubMed Identifier
29926957
Citation
Schwarz F, Derks J, Monje A, Wang HL. Peri-implantitis. J Periodontol. 2018 Jun;89 Suppl 1:S267-S290. doi: 10.1002/JPER.16-0350.
Results Reference
background
PubMed Identifier
30535817
Citation
Solderer A, Kaufmann M, Hofer D, Wiedemeier D, Attin T, Schmidlin PR. Efficacy of chlorhexidine rinses after periodontal or implant surgery: a systematic review. Clin Oral Investig. 2019 Jan;23(1):21-32. doi: 10.1007/s00784-018-2761-y. Epub 2018 Dec 7.
Results Reference
background
PubMed Identifier
31407437
Citation
Daubert DM, Weinstein BF. Biofilm as a risk factor in implant treatment. Periodontol 2000. 2019 Oct;81(1):29-40. doi: 10.1111/prd.12280.
Results Reference
background
PubMed Identifier
10531737
Citation
Besimo CE, Guindy JS, Lewetag D, Meyer J. Prevention of bacterial leakage into and from prefabricated screw-retained crowns on implants in vitro. Int J Oral Maxillofac Implants. 1999 Sep-Oct;14(5):654-60.
Results Reference
background
PubMed Identifier
17076607
Citation
Duarte AR, Rossetti PH, Rossetti LM, Torres SA, Bonachela WC. In vitro sealing ability of two materials at five different implant-abutment surfaces. J Periodontol. 2006 Nov;77(11):1828-32. doi: 10.1902/jop.2006.060101.
Results Reference
background
PubMed Identifier
27611755
Citation
Podhorsky A, Putzier S, Rehmann P, Streckbein P, Domann E, Wostmann B. Bacterial Contamination of the Internal Cavity of Dental Implants After Application of Disinfectant or Sealant Agents Under Cyclic Loading In Vitro. Int J Prosthodont. 2016 Sep-Oct;29(5):493-5. doi: 10.11607/ijp.4546.
Results Reference
background
PubMed Identifier
31405061
Citation
Carinci F, Lauritano D, Bignozzi CA, Pazzi D, Candotto V, Santos de Oliveira P, Scarano A. A New Strategy Against Peri-Implantitis: Antibacterial Internal Coating. Int J Mol Sci. 2019 Aug 9;20(16):3897. doi: 10.3390/ijms20163897.
Results Reference
background
PubMed Identifier
20074465
Citation
D'Ercole S, Tete S, Catamo G, Sammartino G, Femminella B, Tripodi D, Spoto G, Paolantonio M. Microbiological and biochemical effectiveness of an antiseptic gel on the bacterial contamination of the inner space of dental implants: a 3-month human longitudinal study. Int J Immunopathol Pharmacol. 2009 Oct-Dec;22(4):1019-26. doi: 10.1177/039463200902200417.
Results Reference
background
PubMed Identifier
26411835
Citation
Ghannad F, Alkadi LT, Wiebe CB, Shen Y, Haapasalo M, Larjava HS. Intra-operative application of chlorhexidine gel reduces bacterial counts in internal implant cavity. Eur J Oral Sci. 2015 Dec;123(6):425-31. doi: 10.1111/eos.12213. Epub 2015 Sep 28.
Results Reference
background
PubMed Identifier
18672991
Citation
Paolantonio M, Perinetti G, D'Ercole S, Graziani F, Catamo G, Sammartino G, Piccolomini R. Internal decontamination of dental implants: an in vivo randomized microbiologic 6-month trial on the effects of a chlorhexidine gel. J Periodontol. 2008 Aug;79(8):1419-25. doi: 10.1902/jop.2008.070660.
Results Reference
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Antiseptic Effects on the Dental Implant Internal Surface Microbiome

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