Phase II Clinical Trial of Intraoral Grafting of Human Tissue Engineered Oral Mucosa

Study Overview
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Brief Summary
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The purpose of this study is to improve the current standard of care of repairing mouth soft tissue defects.

Detailed Description
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This study will test a tissue equivalent ex vivo produced oral mucosa equivalent(EVPOME), which is a subject's own cells grown on top of a piece of AlloDerm (a commercially available freeze dried human cadaver tissue that is routinely used in present day surgical reconstructive procedures) to create a new piece of soft tissue for use only in that subject's body. The tissue equivalent product will be tested against a non-experimental method of grafts, the gold standard a piece of palatal oral mucosa (POM) to see which works best. Each subject will be randomly assigned to receive either the EVPOME or POM to cover the defect in their mouth. The objective of the study is to assess the safety and efficacy for the use of human EVPOME for soft tissue intraoral grafting procedures compared to the gold standard palatal oral mucosa (POM) graft.

Official Title
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A Randomized, Parallel-group Autogenous ex Vivo Produced Oral Mucosa Equivalent vs. Palatal Oral Mucosa Safety and Efficacy Study in Subjects Requiring Additional Keratinized Oral Mucosa for Dental Implants

Conditions
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Disorder of Oral Mucous Membrane

Intervention / Treatment
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* Biological: EVPOME (autogenous ex vivo produced oral mucosa equivalent)
* Biological: POM (Palatal oral mucosa)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Deficient band (<3mm) of keratinized mucosa prior to or following dental implant placement Surgery to increase width of keratinized mucosa is clinically indicated or requested by the patient to facilitate oral hygiene procedures or to improve esthetics Patients in need of a graft of approximately 15 x 10 x 20 mm in dimension Exclusion Criteria: Subjects with potential medical complications such as evidence of clinically significant (as described by investigators) renal, hepatic, cardiac, endocrine, hematologic, autoimmune, or any systemic disease which may complication execution of the protocol and/or interpretation of results Current radiation therapy or history of radiation therapy treatment to the intraoral donor biopsy site or recipient site for graft placement Documented history of syphilis, HIV, Hepatitis B or C virus Pregnant women or women planning to become pregnant or unwilling to abstain or use double barrier contraceptives during the course of the study Smoking or use of tobacco products within 6 months prior to screening History of either alcohol or drug abuse Subjects taking medications that can result in gingival enlargement/overgrowth (Cyclosporine, Dilantin, calcium channel blockers) Current use of intravenous bisphosphonate or current oral bisphosphate use or a history of bisphosphonate use for over 5 years

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Palatal Oral Mucosa (POM) Graft<br>Standard of care palatal oral mucosa (POM) graft will be taken from the palate and then surgically placed onto the defect area | Biological: POM (Palatal oral mucosa)<br>* POM is a tissue graft harvested from the palate and surgically placed into the defect area<br>|
| Experimental: Ex vivo Produced Oral Mucosa Equivalent<br>Palatal biopsy will be harvested for fabrication of autogenous ex vivo produced oral mucosa equivalent (EVPOME) and then surgically placed onto the defect area | Biological: EVPOME (autogenous ex vivo produced oral mucosa equivalent)<br>* EVPOME is manufactured from the subjects own oral cells and is implanted back in the subjects mouth after an approximately 30 day manufacturing process.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Increase in Zone (Width) of Keratinized Mucosa at Grafted Site | The keratinized mucosa (KM) width will be measured by determining the distance from the crest of the edentulous ridge to the mucogingival line to the nearest millimeter with a Castroviejo caliper. The keratinized mucosa width of study subjects was measured prior to graft placement and then after two weeks, and after 4 weeks. The data provided shows the difference in keratinized mucosa width between the pre surgery measure and the post surgery measure. More mucosa width (positive numbers in mm) is an improvement, negative numbers (a decrease) would be less good. | 2 and 4 weeks post surgical graft | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Graft Contracture | Graft measurements collected at each time point post graft surgery, 2 weeks, 4 weeks, 8 weeks and 24 weeks. Measurements collected, Horizontal Coronal (mm), Horizontal Apical (mm), Vertical between coronal and apical (mm), were used to determine the area of the graft as a trapezoid like shape. The area of the graft at each time point was compared to the area of the graft at the time of implantation (graft surgery) to determine the % of graft contracture from implantation thru each follow-up time point. Less graft contracture is considered a better outcome. | 2, 4, 8 and 24 weeks after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dental implants, deficient keratinized oral mucosa