Wound Healing With Hyaluronic Acid After Alveolar Ridge Preservation

December 15, 2022 updated by: University Hospital, Ghent

A Randomized Controlled Trial Evaluating Hyaluronic Acid as a Wound Healing Agent Following Alveolar Ridge Preservation

After tooth extraction, shrinkage of the bone is expected after 6 months. These changes may hamper dental implant placement and compromise soft tissue aesthetics. Alveolar Ridge Preservation (ARP) includes application of bovine-derived deproteinized bone particles in the extraction site. This technique is widely performed and drastically limits aforementioned volumetric changes.

The amount of bone preservation following ARP is affected by the soft tissue barrier. In an open healing situation, it takes about 4 weeks to have complete soft tissue closure. Faster soft tissue closure could optimize the amount of bone preservation with obvious benefits for implant placement and aesthetics.

Recent presentations showed the application of hyaluronic acid after ARP. However, no evidence can be found in the literature. This study aims to evaluate the wound healing potential of hyaluronic acid following ARP, as this has never been performed, yet seems promising from a biological point of view.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Aim:

This study aims to evaluate the wound healing potential of hyaluronic acid (HA) following alveolar ridge preservation (ARP), as this has never been performed, yet seems promising from a biological point of view.

Sample size calculation:

A sample size calculation using a two-sample pooled t-test was performed in SAS Power and Sample Size based on a comparison of mean overall wound reduction from baseline to 21 days between the control and test group. The calculation was based on finding a mean difference of 20% between these groups with a standard deviation of 21.6 for the control and 21.6 for the test group. A pilot study was executed to obtain these findings as no other data are available. With alpha set at 0.05 and a power of 0.08, the sample size calculation indicated 19 patients to be included per group. To compensate for drop-outs, 25 would be treated with hyaluronic acid and 25 would be treated without.

Clinicians and centers, randomization, allocation concealment and blinding:

3 clinicians linked to the Department of Periodontology and Oral Implantology at UGent - UZ Gent will treat a total of 50 patients. Each clinician will treat at least 10 patients. Patients will be randomly allocated to the 'test group (Hyaluronic acid)' or the 'control group (No hyaluronic acid). An equal number of sealed envelopes will be prepared internally labelled as 'test group' or 'control group'. Just after ARP, a sealed envelope will be randomly selected and opened to reveal further treatment. In case the test group comes out, instructions for the daily application of HA (Gengigel Forte©) will be given. HA will be administered by the patient 3 times per day during 7 days.

The measuring investigator will not be involved in the treatment of any of the patients and will be blinded to allow unbiased registrations.

Surgical procedure:

After screening and having obtained informed consent by the patient, the tooth is extracted and ARP is performed by placing collagen-enriched deproteinized bovine bone mineral (DBBM, Bio-Oss collagen 100 mg or 250 mg, Geistlich Biomaterials, Switserland) in the alveolar socket. Subsequently, a collagen matrix (Mucograft seal, Geistlich Biomaterials, Switserland), is sutured on top to protect the underlying DBBM. At the end of the surgical procedure, the sealed envelope is opened to reveal the allocated treatment and instructions to the patients are given (application of Gengigel Forte© 3 times per day during 7 days).

Intra-surgical registrations:

Intra-surgically, the dimensions of the buccal bone plate will be registered. Papillae are analyzed if they were detached from the bone mesial and distal during extraction. Subsequently, the size of the Mucograft seal (Geistlich Biomaterials, Switserland) is measured. Immediately after ARP, a conebeam computed tomography (CBCT) of the alveolar bone is taken and an intra-oral scan of the soft tissues is performed (for study purposes). Afterwards, an occlusal clinical photograph is taken. The wound dimension is registered by measuring the maximum mesio-distal and bucco-oral dimension of the wound with a periodontal probe to the nearest 0.5 mm (for study purposes).

One-week post-surgery:

One week after ARP, patient's compliance concerning the application of HA 3 times a day is evaluated, as well as the number of painkillers taken. A Visual Analog Scale (VAS) will be filled out by patients to register pain, swelling and bleeding after surgery. (for study purposes) Furthermore, a socket wound healing scoring (SWHS, is given to each extraction wound and another occlusal photograph is taken at the end of the consultation. To evaluate the soft tissue closure, the maximum mesio-distal and bucco-oral dimension of the remaining wound is measured with a periodontal probe to the nearest 0.5 mm. (for study purposes)

Wound closure after 21 days:

Three weeks post-surgery, the maximum mesio-distal and bucco-oral dimension of the remaining wound is measured with a periodontal probe to the nearest 0.5 mm. For each aspect (mesio-distal and bucco-oral) the percentage wound reduction is calculated as follows:

100 - ((Maximum wound dimension after 21 days * 100) / maximum wound dimension immediately after ARP)

The overall wound reduction is calculated as follows:

(Wound reduction at the mesio-distal aspect + wound reduction at the bucco-oral aspect) / 2

SWHS is determined for each wound. Finally, an occlusal clinical photograph is taken.

4 months after surgery: An occlusal photograph is taken to analyze mucosal scarring using the Mucosal Scarring Index (MSI, for study purposes). A second CBCT is made to measure dimensional changes of the alveolar process. A second intra-oral scan is made to measure dimensional changes in buccal soft tissue profile. (standard of care)

Data analysis:

Depending on the distribution of the data, an independent samples t-test or Mann-Whitney U test will be performed on the following parameters:

  • Wound reduction after 21 days (primary outcome)
  • VAS swelling
  • VAS pain
  • Number of painkillers consumed
  • Socket Wound healing score
  • Mucosal scarring index
  • Dimensional changes in the buccal soft tissue profile
  • Dimensional changes of the alveolar process

For the following categorical variables, a Fisher's exact will be performed:

  • Compliance
  • Bleeding

Study Type

Interventional

Enrollment (Actual)

38

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Belgium
      • Ghent, Belgium, 9000
        • University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • At least 18 years old;
  • Good oral hygiene defined as a full-mouth plaque score ≤25%;
  • One or two neighboring teeth;
  • Need for ARP after tooth extraction with >50% buccal bone still present

Exclusion Criteria:

  • Systemic diseases;
  • Smoking;
  • (History) of periodontal disease;
  • Untreated caries lesions

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control
No further treatment after alveolar ridge preservation
Active Comparator: Test
In case the test group comes out, instructions for the daily application of hyaluronic acid (Gengigel Forte©) will be given. Hyaluronic acid will be administered by the patient 3 times per day during 7 days.
Device: Gengigel Forte©
Gengigel (hyaluronic acid) will be administered by the patient 3 times per day during 7 days following alveolar ridge preservation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Wound reduction
Time Frame: Week 3 after ARP
performed by measuring the maximum mesio-distal and bucco-oral dimension of the wound immediately after ARP and after 21 days
Week 3 after ARP

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Compliance
Time Frame: Week 1
patients will be asked if they applied HA 3 times a day as prescribed? Protocol violations will be recorded to see if they have an impact on the outcome (fully compliant patients versus weakly compliant patients).
Week 1
Number of painkillers consumed
Time Frame: Week 1
Week 1
VAS pain
Time Frame: Week 1
Visual Analogue Scale for pain: the patient has to indicate the intensity of pain perception during the first week after surgery on a 10 cm line
Week 1
VAS swelling
Time Frame: Week 1
Visual Analogue Scale for swelling: the patient has to indicate the amount of swelling perception during the first week after surgery on a 10 cm line
Week 1
Bleeding
Time Frame: Week 1
Patients will be asked if they experienced post-operative bleeding
Week 1
Socket wound healing score
Time Frame: Week 1 and 3

This index will be used to assess wound dehiscence, epithelialization, quality of granulation tissue filling the post-extraction socket, and depth between early granulation tissue and wound margin.

Assessments will be performed at performed at 7 and 21 days following surgery using a blunt periodontal probe with millimetric markers and scored as a number between 0 (best) and 4 (worst). In contrast to the study from (Afat et al., 2018), this study will not probe inside the healing wound.
Week 1 and 3
Mucosal scarring index
Time Frame: 4 months
The MSI is a composite index based on five parameters: width, height/contour, color, suture marks, and overall appearance. Each parameter is assessed with a 0-1-2 score, yielding an MSI score ranging from 0 (no scar) to 10 (most extreme scar)
4 months
Dimensional changes in the buccal soft tissue profile
Time Frame: At time of surgery and at 4 months
Immediately after surgery and at 4 months an intra-oral optical scan of the implant site and neighboring teeth will be taken (Trios, 3shape, Copenhagen, Denmark). The region of interest (ROI) will be defined on the 4-month STL files with a trapezoid shape encompassing the following borders (fig. 2): 0.5 mm apical to the midfacial soft tissue level (coronal), 4 mm apical and parallel to the first line (apical), mesial and distal line angle. This ROI may vary between patients due to anatomical variation but will be kept constant in each patient and site over time. The STL images of baseline and follow-up will be superimposed and matched using the best-fit algorithm at the adjacent tooth surfaces. The linear changes in BSP will be calculated by the software and expressed in mm corresponding to the mean distance between the surfaces representing the evaluated time points.
At time of surgery and at 4 months
Dimensional changes of the alveolar process
Time Frame: Immediately after surgery and at 4 months
Comparing CBCT-scan after surgery and after 4 months. First, a line parallel and perpendicular to the tooth axis is drawn. Hereby, bone dimensions can be measured at different vertical heights on the alveolar process. The level of the palatal bone crest at T0 is used as a reference line (level 0). The horizontal dimension of the process is registered at 1, 3, and 5 mm apical to the reference line (level -1, -3, and -5). After performing all measurements on the baseline CBCT (T0), the software will be switched to the superimposed image (T1) so that the measurements can be performed while using the same reference levels
Immediately after surgery and at 4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Ghent

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2020

Primary Completion (Actual)

June 30, 2021

Study Completion (Actual)

January 24, 2022

Study Registration Dates

First Submitted

July 8, 2020

First Submitted That Met QC Criteria

July 8, 2020

First Posted (Actual)

July 13, 2020

Study Record Updates

Last Update Posted (Estimate)

December 20, 2022

Last Update Submitted That Met QC Criteria

December 15, 2022

Last Verified

July 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 07-718

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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