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

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

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

Study Overview

• Status: Terminated
• Conditions: Disorder of Oral Mucous Membrane
• Intervention / Treatment: Biological: POM (Palatal oral mucosa); Biological: EVPOME (autogenous ex vivo produced oral mucosa equivalent)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5018
      • University of Michigan, Department of Oral & Maxxillofacial Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Palatal Oral Mucosa (POM) Graft; 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); POM is a tissue graft harvested from the palate and surgically placed into the defect area
Experimental: Ex vivo Produced Oral Mucosa Equivalent; 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); EVPOME is manufactured from the subjects own oral cells and is implanted back in the subjects mouth after an approximately 30 day manufacturing process.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Graft Blood Flow	Graft blood flow measured using Laser Doppler flowmetry (LDF) of the graft at 2 and 4 weeks after surgery. LDF measurements (perfusion units) are taken at the site of the graft and compared to LDF readings at a contralateral site on the same subject. The comparison is reported as a percent. The percent is derived by dividing the LDF perfusion units at the graft site by the LDF perfusion units at the contralateral site in the same subject. It is not known how many perfusion units are necessary to adequately supply blood to a graft. By comparing the graft site to the contralateral site in the same patient at 2 and 4 weeks post surgery this data may provide more understanding of graft incorporation.	2 and 4 weeks after surgery
Immunohistochemistry Using Anti-CD31 (Cluster of Differentiation 31) to Detect Blood Vessel Growth Into the Graft.	A biopsy of the graft is taken at 4 weeks after engraftment. The biopsy is stained for CD31 (cluster of differentiation 31) which is a marker for blood vessels. The number of blood vessels are counted in a standardized size of field. The number of blood vessels within the standardized field is reported. It is not known how much blood vessel development is necessary for graft success, but this study may provide insight into blood vessel development within EVPOME grafts over time.	4 weeks after graft surgery

Collaborators and Investigators

• Sponsor: Stephen E. Feinberg
• Investigators: Principal Investigator: Stephen E Feinberg, DDS, PhD, MS, University of Michigan

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): January 15, 2019
• Study Completion (Actual): January 15, 2019

Study Registration Dates

• First Submitted: April 12, 2013
• First Submitted That Met QC Criteria: April 12, 2013
• First Posted (Estimate): April 17, 2013

Study Record Updates

• Last Update Posted (Actual): September 5, 2021
• Last Update Submitted That Met QC Criteria: August 9, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: dental implants; deficient keratinized oral mucosa
• Other Study ID Numbers: HUM00065554

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No