Back to resultsA New Drug Delivery System - Silk Fibroin Film Loaded or Not With Insulin on Palatal Mucosa Wound Healing
Primary Purpose
Wound Healing, Insulin, Palate; Wound
Status
Recruiting
Phase
Not Applicable
Locations
Brazil
Study Type
Interventional
Intervention
Palatal Wound
Palatal Wound treated with Silk Fibroin Film
Palatal Wound treated with Insulin-loaded Silk Fibroin Film
Sponsored by
About this trial
This is an interventional treatment trial for Wound Healing focused on measuring Wound Healing, Drug Delivery System, Insulin, Fibroin
Eligibility Criteria
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).
Sites / Locations
- Mauro Pedrine Santamaria and Manuela Maria Viana MiguelRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Sham Comparator
Experimental
Experimental
Arm Label
Control Group (CG)
Blank Film Group (BF)
Insulin-loaded film (IF)
Arm Description
The palatal wound area will not receive any treatment
The palatal wound area will receive silk fibroin film as a dressing
The palatal wound area will receive an insulin-loaded silk fibroin film as a drug delivery system
Outcomes
Primary Outcome Measures
Change in the Remaining wound healing (RWA)
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).
Secondary Outcome Measures
Tissue Thickness (TT)
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.
Epithelialization (E)
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).
Early- wound healing index (EWHI)
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
Tissue Edema (TE)
Tissue edema will be evaluated with the score: 1 = absent; 2 = slight; 3 = moderate; or 4 = severe (Sanz-Moliner et, 2013).
Oral Health Impact Profile
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)
Number of analgesics
Number of analgesics used during 14 days after the procedure will be reported at the same postoperative diary (Tonetti et al. 2017).
Patient Discomfort
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).
Qualitative somatosensory testing (QualST)
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.
Immunologic Analysis
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.
Histological Analysis
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.
Full Information
NCT ID
NCT05171400
First Posted
September 28, 2021
Last Updated
December 23, 2021
Sponsor
Universidade Estadual Paulista Júlio de Mesquita Filho
1. Study Identification
Unique Protocol Identification Number
NCT05171400
Brief Title
A New Drug Delivery System - Silk Fibroin Film Loaded or Not With Insulin on Palatal Mucosa Wound Healing
Official Title
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.
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Recruiting
Study Start Date
July 2, 2021 (Actual)
Primary Completion Date
August 2, 2022 (Anticipated)
Study Completion Date
December 20, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Universidade Estadual Paulista Júlio de Mesquita Filho
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Wound Healing, Insulin, Palate; Wound
Keywords
Wound Healing, Drug Delivery System, Insulin, Fibroin
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
This is a double-blind, parallel, superiority, randomized clinical trial with 3 months of follow-up.
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
75 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Control Group (CG)
Arm Type
Sham Comparator
Arm Description
The palatal wound area will not receive any treatment
Arm Title
Blank Film Group (BF)
Arm Type
Experimental
Arm Description
The palatal wound area will receive silk fibroin film as a dressing
Arm Title
Insulin-loaded film (IF)
Arm Type
Experimental
Arm Description
The palatal wound area will receive an insulin-loaded silk fibroin film as a drug delivery system
Intervention Type
Procedure
Intervention Name(s)
Palatal Wound
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Palatal Wound treated with Silk Fibroin Film
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Palatal Wound treated with Insulin-loaded Silk Fibroin Film
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in the Remaining wound healing (RWA)
Description
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).
Time Frame
90 days.
Secondary Outcome Measure Information:
Title
Tissue Thickness (TT)
Description
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.
Time Frame
90 days
Title
Epithelialization (E)
Description
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).
Time Frame
90 days
Title
Early- wound healing index (EWHI)
Description
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
Time Frame
14 days
Title
Tissue Edema (TE)
Description
Tissue edema will be evaluated with the score: 1 = absent; 2 = slight; 3 = moderate; or 4 = severe (Sanz-Moliner et, 2013).
Time Frame
7 days
Title
Oral Health Impact Profile
Description
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)
Time Frame
14 days
Title
Number of analgesics
Description
Number of analgesics used during 14 days after the procedure will be reported at the same postoperative diary (Tonetti et al. 2017).
Time Frame
14 days
Title
Patient Discomfort
Description
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).
Time Frame
14 days
Title
Qualitative somatosensory testing (QualST)
Description
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.
Time Frame
14 days
Title
Immunologic Analysis
Description
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.
Time Frame
7 days
Title
Histological Analysis
Description
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.
Time Frame
180 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mauro P Santamaria, PhD
Phone
(12) 39479055
Ext
+55
Email
mauro.santamaria@unesp.br
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mauro P Santamaria, PhD
Organizational Affiliation
Sao Paulo State University - Brazil
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Manuela Maria V Miguel, MS
Organizational Affiliation
Sao Paulo State University - Brazil
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mauro Pedrine Santamaria and Manuela Maria Viana Miguel
City
São José Dos Campos
State/Province
Sao Paulo
ZIP/Postal Code
12245000
Country
Brazil
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Data will be available at the end of the study after a direct request
IPD Sharing Time Frame
After the study completion.
Citations:
PubMed Identifier
27756117
Citation
Teuschl AH, Zipperle J, Huber-Gries C, Kaplan DL. Silk fibroin based carrier system for delivery of fibrinogen and thrombin as coagulant supplements. J Biomed Mater Res A. 2017 Mar;105(3):687-696. doi: 10.1002/jbm.a.35940. Epub 2016 Nov 7.
Results Reference
background
PubMed Identifier
30475285
Citation
Kamalathevan P, Ooi PS, Loo YL. Silk-Based Biomaterials in Cutaneous Wound Healing: A Systematic Review. Adv Skin Wound Care. 2018 Dec;31(12):565-573. doi: 10.1097/01.ASW.0000546233.35130.a9.
Results Reference
background
PubMed Identifier
22564234
Citation
Chen X, Liu Y, Zhang X. Topical insulin application improves healing by regulating the wound inflammatory response. Wound Repair Regen. 2012 May-Jun;20(3):425-34. doi: 10.1111/j.1524-475X.2012.00792.x.
Results Reference
background
PubMed Identifier
25373688
Citation
Dias SB, Fonseca MV, Dos Santos NC, Mathias IF, Martinho FC, Junior MS, Jardini MA, Santamaria MP. Effect of GaAIAs low-level laser therapy on the healing of human palate mucosa after connective tissue graft harvesting: randomized clinical trial. Lasers Med Sci. 2015 Aug;30(6):1695-702. doi: 10.1007/s10103-014-1685-2. Epub 2014 Nov 6.
Results Reference
background
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A New Drug Delivery System - Silk Fibroin Film Loaded or Not With Insulin on Palatal Mucosa Wound Healing
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