A New Drug Delivery System - Silk Fibroin Film Loaded or Not With Insulin on Palatal Mucosa Wound Healing

December 23, 2021 updated by: Mauro Pedrine Santamaria, Universidade Estadual Paulista Júlio de Mesquita Filho

A New Drug Delivery System - Silk Fibroin Film Loaded or Not With Insulin on Palatal Mucosa Wound Healing: in Vitro Study and a Randomized Clinical Trial.

The aim of the present study is to evaluate using clinical, patient-centered, immunological, microbiological, and histological parameters, the effect of silk fibroin films loaded or not with insulin in the repair of palatal mucosa open wounds.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

There are several types of periodontal and peri-implant soft tissue defects that require surgical treatment to reestablishment function and aesthetics. Therefore, surgical procedures for the reconstruction of the gingival and peri-implant tissues are routinely performed. However, these procedures do not always have predictable outcomes, and problems with the wound healing process can occur, which can impair the outcomes. To overcome this problem, new materials, drugs, and devices have been used to improve the results of surgical procedures. The present study is a controlled clinical trial that will include seventy-five patients with an indication of anterior maxillary tooth extraction for ridge preservation. The ridge preservation will be performed and a free gingival graft harvest from the palatal mucosa will be used to seal the socket entrance. Thereafter, the palatal wound will be randomly assigned into 3 groups: Control Group (C; n=25): open wound on palatal mucosa that will receive no treatment. Blank Film Group (BF; n=25): open wound on palatal mucosa that will receive silk fibroin film as dressing. Insulin-loaded film (IF; n=25): open wound on palatal mucosa that will receive an insulin-loaded silk fibroin film as a delivery system. Clinical, immunological, histological, and microbiome parameters will be analyzed.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
75

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Brazil
    • Sao Paulo
      • São José Dos Campos, Sao Paulo, Brazil, 12245000
        • Recruiting
        • Mauro Pedrine Santamaria and Manuela Maria Viana Miguel

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with at least 18 years, systemically healthy, with good oral hygiene, assessed by plaque index and gingival index less than 25% (Ainamo, Bay, 1975);
  • Patients with no morphological or pathological conditions on the palatine donor area;
  • Patients who present indication for extraction and ridge preservation;
  • The tooth included in the study, as well as, the adjacent teeth do not present loss of periodontal insertion;
  • Patients who agreed to and sign the formal consent to participate in the study after receiving an explanation of risks and benefits from an individual who was not a member of the present study (Resolution no. 118 - May, 2012, and Ethics and Code of Professional Conduct in Dentistry - 118/12).

Exclusion Criteria:

  • Patients with systemic problems (cardiovascular, blood dyscrasias, immunodeficiency, and diabetes, among others) that will contraindicate the surgical procedure;
  • Patients taking medications known to interfere with the wound healing process or that contraindicate the surgical procedure;
  • Smokers patients;
  • Pregnant or lactating patients;
  • Patients who had had periodontal surgery on the study area;
  • Patients who presents opportunistic oral lesions, mainly colonized the palate region;
  • Use of dental prosthesis with palatal cover;
  • Thin palatal mucosa (~2.0mm).

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Sham Comparator: Control Group (CG)
The palatal wound area will not receive any treatment
Procedure: Palatal Wound
With the goal to harvest the free gingival graft (FGG), an 8mm diameter scalpel will be used to ensure standardized wounds. Thereafter, a 2-mm thick FGG will be removed. The wound area will receive 4.0 silk sutures.
Experimental: Blank Film Group (BF)
The palatal wound area will receive silk fibroin film as a dressing
Procedure: Palatal Wound
With the goal to harvest the free gingival graft (FGG), an 8mm diameter scalpel will be used to ensure standardized wounds. Thereafter, a 2-mm thick FGG will be removed. The wound area will receive 4.0 silk sutures.
Device: Palatal Wound treated with Silk Fibroin Film
With the goal to harvest the free gingival graft (FGG), an 8mm diameter scalpel will be used to ensure standardized wounds. Thereafter, a 2-mm thick FGG will be removed. The wound area will receive a silk fibroin film and 4.0 silk sutures.
Experimental: Insulin-loaded film (IF)
The palatal wound area will receive an insulin-loaded silk fibroin film as a drug delivery system
Procedure: Palatal Wound
With the goal to harvest the free gingival graft (FGG), an 8mm diameter scalpel will be used to ensure standardized wounds. Thereafter, a 2-mm thick FGG will be removed. The wound area will receive 4.0 silk sutures.
Device: Palatal Wound treated with Insulin-loaded Silk Fibroin Film
With the goal to harvest the free gingival graft (FGG), an 8mm diameter scalpel will be used to ensure standardized wounds. Thereafter, a 2-mm thick FGG will be removed. The wound area will receive a silk fibroin film loaded with insulin and 4.0 silk sutures.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in the Remaining wound healing (RWA)
Time Frame: 90 days.
Photographs will be taken from palatal wound with brightness, distance, and angle standardized. A scale will be placed in the palate as a reference to measure the area. These photographs will be exported to an image software (Image J - NIH, Bethesda, USA), and the wound area will be measured in square millimeters (Dias et al., 2015).
90 days.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Tissue Thickness (TT)
Time Frame: 90 days
Tissue thickness of palatine masticatory mucosa will be assessed by a Cone Beam Computed Tomographic (CBCT). In order to standardize the volume measures, the FGG harvested stent, made of 1 mm thick rigid acrylic plates in vacuum plasticizer with radiopaque material, will be used by the patient at the time of the CBCT image acquisition.
90 days
Epithelialization (E)
Time Frame: 90 days
Wound will be colored with Replack (Dentisply - York, Pensilvânia - USA) and quantity measured by Image J program. Then, with the total area of the wound, the epithelization % will be calculated (Ozcelik et al. 2008).
90 days
Early- wound healing index (EWHI)
Time Frame: 14 days

According to Fickl et al. 2014 any modification in wound healing will be evaluated in five different degrees:

  • Complete wound closure with an absence of fibrin on the palate;
  • Complete wound closure with the presence of a fibrin line on palate;
  • Complete wound closure with the presence of a clot with fibrin on palate
  • Incomplete wound closure with partial tissue necrosis on palate;
  • Incomplete wound closure with total tissue necrosis on palate
14 days
Tissue Edema (TE)
Time Frame: 7 days
Tissue edema will be evaluated with the score: 1 = absent; 2 = slight; 3 = moderate; or 4 = severe (Sanz-Moliner et, 2013).
7 days
Oral Health Impact Profile
Time Frame: 14 days
Will be evaluated from a questionnaire with 14 questions based on 7 domains: functional limitations, physical pain, psychological discomfort, physical disability, psychological deficiency and social deficiency. The patient should respond to the questions within 14 days after the surgical procedure, performing a postoperative diary. For each question an answer must be given, represented in numbers, being: 0- Never; 1- Almost never; 2-Occasionally; 3-Quite frequent; 4-Very common; 5-I do not know (Tonetti MS et al. 2017)
14 days
Number of analgesics
Time Frame: 14 days
Number of analgesics used during 14 days after the procedure will be reported at the same postoperative diary (Tonetti et al. 2017).
14 days
Patient Discomfort
Time Frame: 14 days
By a visual analogic scale (VAS) of 100 mm to assess discomfort, patients will report pain diary during the 14 days after surgery. Scale extremes will be "no pain" to "extreme." (Tonetti et al. 2017).
14 days
Qualitative somatosensory testing (QualST)
Time Frame: 14 days
This analysis will evaluate somatosensorial profiles and pain conditions. For this, different stimulus will be performed on the wound and the following tests will be applied: (1) Touch stimulus will be applied with a swab by a single application for 1-2 sec in the wound; (2) Cold stimulus will be applied by a stainless steel dental spatula (kept cool in ice water, approximately 0 °C) with wound direct contact during 1-2 sec; (3) The pinprick stimulus will be performed with a periodontal probe with moderate force on the wound area for 1-2 s (Baad-Hansen et al, 2013) Patient will report hypersensitivity, hyposensitivity, or normosensitivity to touch, cold and painful stimulus.
14 days
Immunologic Analysis
Time Frame: 7 days
With the goal to obtain baseline data for this parameter, crevicular gingival fluid from the gingival area next to the donor area will be collected previous surgery. An absorbent paper (PerioPaper, Oraflow, Plainview, NY, EUA) will be placed at wound edges without pressure during 40s. Collects with blood contamination will be discarded. Samples will be stored into a sterilized Eppendorf containing 100 μL Phosphate Buffer Saline 0.05% Tween 2 (PBS) at - 80 C. Growth factors (VEGF and EGF), chemokines (MIP-1α, MCP-1α), and cytokines (IL1β, IL6, IL10, TNFα) levels will be determinate by the multiplex assay. Moreover, MMP-2, MMP-9, TIMP-1, TIMP-2 will be measured by the same commercial human commercial kit.
7 days
Histological Analysis
Time Frame: 180 days
CTG will be harvested from the palatal area, the same area that received FGG protocol previously, using the same harvesting stent, during implant therapy. After CTG be harvested, a 2-mm thick will be removed from the graft (Azar et al., 2019) to perform biopsy analysis aiming to observe histological changes during healing process by previously use of silk fibroin film, charged or not with insulin, and spontaneous repair. The specimens will be immersed in 10% formalin for histological analysis which will be stained with hematoxylin-eosin and Masson's trichrome.
180 days

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Universidade Estadual Paulista Júlio de Mesquita Filho

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Mauro P Santamaria, PhD, Sao Paulo State University - Brazil
  • Principal Investigator: Manuela Maria V Miguel, MS, Sao Paulo State University - Brazil

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 2, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 2, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 20, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 28, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 23, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 28, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 28, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 23, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UEPJMF11

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Data will be available at the end of the study after a direct request

IPD Sharing Time Frame

After the study completion.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Informed Consent Form (ICF)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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