Peri-implantitisNCT06618560
Effect of Enamel Matrix Derivative or Hyaluronic Acid on Non-Surgical Treatment of Peri-Implantitis
A study testing Enamel Matrix Derivative application and Hyaluronic Acid (HA) in people with Peri-implantitis, run by Gazi University.
Trial summary
The aim of the present randomized controlled clinical study is to compare the clinical, radiographic, and patient-centered efficacy of adjunctive application of either enamel matrix derivative (EMD) or hyaluronic acid (HA) gel in conjunction with non-surgical therapy compared to non-surgical therapy alone following a… Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Peri-implantitis
- What is being tested?
- Enamel Matrix Derivative application and Hyaluronic Acid (HA)
- Type of treatment
- Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- 1 Nov 2024to 30 Jan 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Systemically healthy and ≥18 years of age,
- Implants with an SLA® or SLActive® surface (Straumann Dental Implant System, Institute Straumann AG) have been in function for more than 1 year,
- Implant-supported prostheses accessible for self-performed plaque control and submarginal instrumentation,
- Absence of implant mobility.
Who cannot join
- Full-mouth plaque score (FMPS) \> 20%
- Full-mouth bleeding score (FMBS) \> 20%
- Cigarette smoking \> 10 cig./day,
- Diagnosed with active periodontal disease,
- Having acute or chronic medical conditions or undergoing medications, such as intravenous amino-bisphosphonates, immunosuppressive drugs, and chemotherapy, that could interfere with the treatment outcome,
- Receiving antibiotic treatment in the previous 3 months.
Trial locations and contacts
No sites are listed yet.
Andrea Roccuzzo, PhD contact
About this study
Official title: Adjunctive Local Application of Enamel Matrix Derivative or Hyaluronic Acid to Non-surgical Mechanical Treatment of Peri-implantitis: a 12-month Randomized Controlled Clinical Trial
The aim of the present randomized controlled clinical study is to compare the clinical, radiographic, and patient-centered efficacy of adjunctive application of either enamel matrix derivative (EMD) or hyaluronic acid (HA) gel in conjunction with non-surgical therapy compared to non-surgical therapy alone following a 12-month healing period.
Therefore, the following question related to the study is raised:
Read more
- Does the adjunctive local application of EMD or HA to non-surgical submucosal mechanical treatment of peri-implantitis result in better clinical, radiographic, and patient-centered outcomes compared to non-surgical therapy alone?
A total of 60 patients referred to the Gazi University Department of Periodontology, will be randomly assigned to receive the local application of EMD or HA in combination with non-surgical submucosal mechanical treatment of peri-implantitis or non-surgical therapy alone. Clinical measurements will be recorded at baseline, 3, 6, and 12 months after surgeries. Patient oral health related to the treatment procedures using a written questionnaire [Oral Health Impact Profile (OHIP-14)] and post-treatment pain and overall patient satisfaction about treatment modalities responses will be evaluated prior to treatment and 3, 6, and 12 months following therapy.
Read the detailed description
Peri-implantitis is considered a growing public health problem in implant dentistry due to its higher prevalence and non-linear accelerating progression pattern. Hence, it is imperative to apply effective treatment strategies to manage this pathological condition. The existing evidence has shown unpredictable therapeutic strategies for peri-implantitis. Conventional non-surgical treatment procedures based on the removal of biofilm accumulation and debridement/instrumentation of the implant surface have exhibited limited disease resolution and persistent inflammation following therapy. Therefore, the application of adjunctive chemotherapeutic bioagents may provide greater disease resolution and reduce the need for surgical treatment.
The application of EMD as an adjunctive measure in peri-implantitis treatment has been suggested to provide favorable outcomes by accelerating wound healing, reducing inflammation, having antimicrobial and antiseptic effects, and osteopromotive features. Although some studies exhibited clinical and radiographic efficacy of EMD in augmentative and non-augmentative surgical management of peri-implantitis, there is no study in the available literature analyzing the effects of flapless application of EMD in non-surgical therapy of peri-implantitis. Cross-linked HA, which has recently been recognized as a featured adjuvant chemotherapeutic bioagent, has also been shown to have beneficial effects in periodontal wound healing and soft and hard tissue regeneration. The use of high-molecular-weight HA has been demonstrated to alter bacterial colonization in the advanced stage of peri-implantitis. However, there is limited evidence about the therapeutic effect of cross-linked HA in peri-implantitis management.
The hypothesis of the study is that the application of EMD and cross-linked HA adjunct to non-surgical therapy could lead to superior outcomes compared to non-surgical therapy alone in peri-implantitis treatment. The null-hypothesis (H0) is that no statistically significant difference in terms of the mean change of probing depth (PD) values after 12 months would be detected among all the study groups.
The aim of the present randomized controlled clinical study is to compare the clinical, radiographic, and patient-centered efficacy of adjunctive application of either enamel matrix derivative (EMD) or hyaluronic acid (HA) gel in conjunction with non-surgical therapy compared to non-surgical therapy alone following a 12-month healing period.
- Conditions
- Peri-implantitis
- Being tested
- Enamel Matrix Derivative application, Hyaluronic Acid (HA), Control
- Keywords
- enamel matrix proteins, hyaluronic acid, peri-implantitis, non-surgical treatment
- Medical subject headings
- Peri-Implantitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Enamel Matrix Derivative applicationDevice
After submarginal instrumentation (i.e., titanium curettes plus oscillating chitosan brush), implant surfaces will be conditioned for 2 min with 24% ethylene-diaminetetraacetate EDTA (PrefGel®, Institut Straumann AG). Then, the sites will be completely rinsed with saline solution and thoroughly dried with air. Repeated irrigation and air-drying will be done in the area until complete bleeding control with sterile gauzes. Then EMD (Emdogain®, Institut Straumann AG) will be gently applied with a blunt-tipped sterile syringe until overflowing from the mucosal margin.
Hyaluronic Acid (HA)Device
After submarginal instrumentation of the implant surface (i.e., titanium curettes plus oscillating chitosan brush), the cross-linked hyaluronic acid gel composed of a mixture of cross-linked (1.6%) and natural (0.2%) will be will be implemented to the peri-implant pockets.
ControlProcedure or surgery
Implants allocated to the control group will be treated with the same sub-marginal instrumentation (i.e., titanium curettes plus oscillating chitosan brush). Implant surface will be irrigated with with sterile saline.
| Study group | Role | What they receive |
|---|---|---|
| Test Group 1: EMD group | Active comparator | After submarginal instrumentation (i.e., titanium curettes plus oscillating chitosan brush), implant surfaces will be conditioned for 2 min with 24% ethylene-diaminetetraacetate EDTA (PrefGel®, Institut Straumann AG). Then, the sites will be completely rinsed with saline solution and thoroughly dried with air. Repeated irrigation and air-drying will be done in the area until complete bleeding control with sterile gauzes. Then EMD (Emdogain®, Institut Straumann AG) will be gently applied with a blunt-tipped sterile syringe until overflowing from the mucosal margin. Receives: Device: Enamel Matrix Derivative application |
| Test Group 2: HA group | Active comparator | After submarginal instrumentation of the implant surface (i.e., titanium curettes plus oscillating chitosan brush), the cross-linked hyaluronic acid gel composed of a mixture of cross-linked (1.6%) and natural (0.2%) will be will be implemented to the peri-implant pockets. Receives: Device: Hyaluronic Acid (HA) |
| Control group | Placebo comparator | Implants allocated to the control group will be treated with the same sub-marginal instrumentation (i.e., titanium curettes plus oscillating chitosan brush). Implant surface will be irrigated with with sterile saline. Receives: Procedure: Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in peri-implant pocket depth
Peri-implant pocket depth (PPD) values will be measured at six sites of each implant. The mean PPD change will be calculated as the difference between the 12-month follow-up PPD relative to the baseline PPD.
Measured: 12 months after the treatment
Secondary outcomes (4)
Treatment success (%)
Treatment success (%) will be considered as PPD ≤ 5 mm with no bleeding on probing (PPD) (more than one point) or suppuration (SUP) and no further bone loss
Measured: 12 months after the treatment
Disease resolution (%)
Disease resolution (%) will be considered as PPD≥5 mm without any BOP or SUP and complete radiographic bone fill
Measured: 12 months after the treatment
Oral Health Impact Profile 14
Patient oral health related to the treatment procedures will be evaluated using a written questionnaire [Oral Health Impact Profile (OHIP-14)] prior to treatment and at 12 months after the treatment.
Measured: 12 months after the treatment
Post-treatment pain
Patients\' responses will be scored on a visual analog scale (VAS, 100 mm). The VAS-pain will be scored from 0 (no pain) to 10 (the worst possible pain).
Measured: 12 months after the treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2024
- Study start1 Nov 2024 (estimated)
- Primary completion15 Jan 2026 (estimated)
- Study completion30 Jan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Peri-implantitisStudies of the same condition, open and under way.
- More trials run by Gazi UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Gazi University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sıla Çağrı İşler, Gazi University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06618560
- Sponsor's protocol ID
- E-66291034-202.3.02-2928
- Status last verified
- Sep 2024
- First submitted
- 26 Sep 2024
- Last updated
- 1 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: It is preferred to share all IPD collected throughout the study after the study will be completed and at the publication stage.
Publications
Soriano-Lerma A, Magan-Fernandez A, Gijon J, Sanchez-Fernandez E, Soriano M, Garcia-Salcedo JA, Mesa F. Short-term effects of hyaluronic acid on the subgingival microbiome in peri-implantitis: A randomized controlled clinical trial. J Periodontol. 2020 Jun;91(6):734-745. doi: 10.1002/JPER.19-0184. Epub 2019 Oct 18.
PubMed 31577041Isehed C, Svenson B, Lundberg P, Holmlund A. Surgical treatment of peri-implantitis using enamel matrix derivative, an RCT: 3- and 5-year follow-up. J Clin Periodontol. 2018 Jun;45(6):744-753. doi: 10.1111/jcpe.12894. Epub 2018 Apr 26.
PubMed 29574866Khan SN, Koldsland OC, Roos-Jansaker AM, Wohlfahrt JC, Verket A, Mdala I, Magnusson A, Salvesen E, Hjortsjo C. Non-surgical treatment of mild to moderate peri-implantitis with an oscillating chitosan brush or a titanium curette-12-month follow-up of a multicenter randomized clinical trial. Clin Oral Implants Res. 2023 Jul;34(7):684-697. doi: 10.1111/clr.14078. Epub 2023 May 3.
PubMed 37139538
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjunctive Local Application of Enamel Matrix Derivative or Hyaluronic Acid to Non-surgical Mechanical Treatment of Peri-implantitis: a 12-month Randomized Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT06618560
- Acronym / sponsor ID
- E-66291034-202.3.02-2928
- Conditions
- Peri-implantitis
- Keywords
- enamel matrix proteins, hyaluronic acid, peri-implantitis, non-surgical treatment
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Gazi UniversityUniversity, hospital or other
- Study start
- 1 Nov 2024 (estimated)
- Primary completion
- 15 Jan 2026 (estimated)
- Study completion
- 30 Jan 2026 (estimated)
- First posted
- 1 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the present randomized controlled clinical study is to compare the clinical, radiographic, and patient-centered efficacy of adjunctive application of either enamel matrix derivative (EMD) or hyaluronic acid (HA) gel in conjunction with non-surgical therapy compared to non-surgical therapy alone following a 12-month healing period.
Therefore, the following question related to the study is raised:
- Does the adjunctive local application of EMD or HA to non-surgical submucosal mechanical treatment of peri-implantitis result in better clinical, radiographic, and patient-centered outcomes compared to non-surgical therapy alone?
A total of 60 patients referred to the Gazi University Department of Periodontology, will be randomly assigned to receive the local application of EMD or HA in combination with non-surgical submucosal mechanical treatment of peri-implantitis or non-surgical therapy alone. Clinical measurements will be recorded at baseline, 3, 6, and 12 months after surgeries. Patient oral health related to the treatment procedures using a written questionnaire [Oral Health Impact Profile (OHIP-14)] and post-treatment pain and overall patient satisfaction about treatment modalities responses will be evaluated prior to treatment and 3, 6, and 12 months following therapy.
Detailed description
Peri-implantitis is considered a growing public health problem in implant dentistry due to its higher prevalence and non-linear accelerating progression pattern. Hence, it is imperative to apply effective treatment strategies to manage this pathological condition. The existing evidence has shown unpredictable therapeutic strategies for peri-implantitis. Conventional non-surgical treatment procedures based on the removal of biofilm accumulation and debridement/instrumentation of the implant surface have exhibited limited disease resolution and persistent inflammation following therapy. Therefore, the application of adjunctive chemotherapeutic bioagents may provide greater disease resolution and reduce the need for surgical treatment.
The application of EMD as an adjunctive measure in peri-implantitis treatment has been suggested to provide favorable outcomes by accelerating wound healing, reducing inflammation, having antimicrobial and antiseptic effects, and osteopromotive features. Although some studies exhibited clinical and radiographic efficacy of EMD in augmentative and non-augmentative surgical management of peri-implantitis, there is no study in the available literature analyzing the effects of flapless application of EMD in non-surgical therapy of peri-implantitis. Cross-linked HA, which has recently been recognized as a featured adjuvant chemotherapeutic bioagent, has also been shown to have beneficial effects in periodontal wound healing and soft and hard tissue regeneration. The use of high-molecular-weight HA has been demonstrated to alter bacterial colonization in the advanced stage of peri-implantitis. However, there is limited evidence about the therapeutic effect of cross-linked HA in peri-implantitis management.
The hypothesis of the study is that the application of EMD and cross-linked HA adjunct to non-surgical therapy could lead to superior outcomes compared to non-surgical therapy alone in peri-implantitis treatment. The null-hypothesis (H0) is that no statistically significant difference in terms of the mean change of probing depth (PD) values after 12 months would be detected among all the study groups.
The aim of the present randomized controlled clinical study is to compare the clinical, radiographic, and patient-centered efficacy of adjunctive application of either enamel matrix derivative (EMD) or hyaluronic acid (HA) gel in conjunction with non-surgical therapy compared to non-surgical therapy alone following a 12-month healing period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Test Group 1: EMD group | Active comparator | Device: Enamel Matrix Derivative applicationAfter submarginal instrumentation (i.e., titanium curettes plus oscillating chitosan brush), implant surfaces will be conditioned for 2 min with 24% ethylene-diaminetetraacetate EDTA (PrefGel®, Institut Straumann AG). Then, the sites will be completely rinsed with saline solution and thoroughly dried with air. Repeated irrigation and air-drying will be done in the area until complete bleeding control with sterile gauzes. Then EMD (Emdogain®, Institut Straumann AG) will be gently applied with a blunt-tipped sterile syringe until overflowing from the mucosal margin. |
| Test Group 2: HA group | Active comparator | Device: Hyaluronic Acid (HA)After submarginal instrumentation of the implant surface (i.e., titanium curettes plus oscillating chitosan brush), the cross-linked hyaluronic acid gel composed of a mixture of cross-linked (1.6%) and natural (0.2%) will be will be implemented to the peri-implant pockets. |
| Control group | Placebo comparator | Procedure: ControlImplants allocated to the control group will be treated with the same sub-marginal instrumentation (i.e., titanium curettes plus oscillating chitosan brush). Implant surface will be irrigated with with sterile saline. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Systemically healthy and ≥18 years of age,
- Implants with an SLA® or SLActive® surface (Straumann Dental Implant System, Institute Straumann AG) have been in function for more than 1 year,
- Implant-supported prostheses accessible for self-performed plaque control and submarginal instrumentation,
- Absence of implant mobility.
Key exclusion criteria (6 listed)
- Full-mouth plaque score (FMPS) \> 20%
- Full-mouth bleeding score (FMBS) \> 20%
- Cigarette smoking \> 10 cig./day,
- Diagnosed with active periodontal disease,
- Having acute or chronic medical conditions or undergoing medications, such as intravenous amino-bisphosphonates, immunosuppressive drugs, and chemotherapy, that could interfere with the treatment outcome,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Enamel Matrix Derivative applicationAfter submarginal instrumentation (i.e., titanium curettes plus oscillating chitosan brush), implant surfaces will be conditioned for 2 min with 24% ethylene-diaminetetraacetate EDTA (PrefGel®, Institut Straumann AG). Then, the sites will be completely rinsed with saline solution and thoroughly dried with air. Repeated irrigation and air-drying will be done in the area until complete bleeding control with sterile gauzes. Then EMD (Emdogain®, Institut Straumann AG) will be gently applied with a blunt-tipped sterile syringe until overflowing from the mucosal margin. | Device | Test Group 1: EMD group |
| Hyaluronic Acid (HA)After submarginal instrumentation of the implant surface (i.e., titanium curettes plus oscillating chitosan brush), the cross-linked hyaluronic acid gel composed of a mixture of cross-linked (1.6%) and natural (0.2%) will be will be implemented to the peri-implant pockets. | Device | Test Group 2: HA group |
| ControlImplants allocated to the control group will be treated with the same sub-marginal instrumentation (i.e., titanium curettes plus oscillating chitosan brush). Implant surface will be irrigated with with sterile saline. | Procedure or surgery | Control group |
Primary outcome
Change in peri-implant pocket depth
Time frame: 12 months after the treatment
Peri-implant pocket depth (PPD) values will be measured at six sites of each implant. The mean PPD change will be calculated as the difference between the 12-month follow-up PPD relative to the baseline PPD.
4 secondary outcomes
Treatment success (%)
Time frame: 12 months after the treatment
Disease resolution (%)
Time frame: 12 months after the treatment
Oral Health Impact Profile 14
Time frame: 12 months after the treatment
Post-treatment pain
Time frame: 12 months after the treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2024.
- Background: PubMed 31577041Soriano-Lerma A, Magan-Fernandez A, Gijon J, Sanchez-Fernandez E, Soriano M, Garcia-Salcedo JA, Mesa F. Short-term effects of hyaluronic acid on the subgingival microbiome in peri-implantitis: A randomized controlled clinical trial. J Periodontol. 2020 Jun;91(6):734-745. doi: 10.1002/JPER.19-0184. Epub 2019 Oct 18.
- Background: PubMed 29574866Isehed C, Svenson B, Lundberg P, Holmlund A. Surgical treatment of peri-implantitis using enamel matrix derivative, an RCT: 3- and 5-year follow-up. J Clin Periodontol. 2018 Jun;45(6):744-753. doi: 10.1111/jcpe.12894. Epub 2018 Apr 26.
- Background: PubMed 37139538Khan SN, Koldsland OC, Roos-Jansaker AM, Wohlfahrt JC, Verket A, Mdala I, Magnusson A, Salvesen E, Hjortsjo C. Non-surgical treatment of mild to moderate peri-implantitis with an oscillating chitosan brush or a titanium curette-12-month follow-up of a multicenter randomized clinical trial. Clin Oral Implants Res. 2023 Jul;34(7):684-697. doi: 10.1111/clr.14078. Epub 2023 May 3.
- Individual participant dataSharing planned: No. It is preferred to share all IPD collected throughout the study after the study will be completed and at the publication stage.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrea Roccuzzo, PhD contact
Questions about this trial
What is this clinical trial studying?
A study testing Enamel Matrix Derivative application and Hyaluronic Acid (HA) in people with Peri-implantitis, run by Gazi University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sila Cagri Associate Professor, PhD (+90 312 2034232, silaisler@gazi.edu.tr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in peri-implant pocket depth (time frame: 12 months after the treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06618560, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2024.