Disorder of Oral Mucous Membrane
Conditions
Keywords
dental implants, deficient keratinized oral mucosa
Brief summary
The purpose of this study is to improve the current standard of care of repairing mouth soft tissue defects.
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.
Interventions
BIOLOGICALEVPOME (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.
BIOLOGICALPOM (Palatal oral mucosa)
POM is a tissue graft harvested from the palate and surgically placed into the defect area
Sponsors
Stephen E. Feinberg
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Increase in Zone (Width) of Keratinized Mucosa at Grafted Site | 2 and 4 weeks post surgical graft | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Graft Contracture | 2, 4, 8 and 24 weeks after surgery | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Graft Blood Flow | 2 and 4 weeks after surgery | 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. |
| Immunohistochemistry Using Anti-CD31 (Cluster of Differentiation 31) to Detect Blood Vessel Growth Into the Graft. | 4 weeks after graft surgery | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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
POM (Palatal oral mucosa): POM is a tissue graft harvested from the palate and surgically placed into the defect area | 10 |
| 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
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. | 8 |
| Total | 18 |
Baseline characteristics
| Characteristic | Palatal Oral Mucosa (POM) Graft | Ex Vivo Produced Oral Mucosa Equivalent | Total |
|---|---|---|---|
| Age, Customized Age 18 to 80 Years | 10 Participants | 8 Participants | 18 Participants |
| Deficient band of keratinized mucosa | 10 Participants | 8 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 8 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 3 Participants |
| Sex/Gender, Customized Female | 6 participants | 7 participants | 13 participants |
| Sex/Gender, Customized Male | 4 participants | 1 participants | 5 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 8 |
| other Total, other adverse events | 6 / 10 | 1 / 8 |
| serious Total, serious adverse events | 0 / 10 | 0 / 8 |
Outcome results
Primary
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.
Time frame: 2 and 4 weeks post surgical graft
Population: Pregraft data for this outcome was not collected for the first subject, the protocol was written to collect the pregraft measurement after the first subject completed POM graft. For this reason there are only 7 data points in the POM arm of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Palatal Oral Mucosa (POM) Graft | Clinical Increase in Zone (Width) of Keratinized Mucosa at Grafted Site | 2 Week increase in keratinized mucosa | 6.1 millimeters | Standard Deviation 1.9 |
| Palatal Oral Mucosa (POM) Graft | Clinical Increase in Zone (Width) of Keratinized Mucosa at Grafted Site | 4 week increase in keratinized mucosa | 5.1 millimeters | Standard Deviation 1.4 |
| Ex Vivo Produced Oral Mucosa Equivalent | Clinical Increase in Zone (Width) of Keratinized Mucosa at Grafted Site | 2 Week increase in keratinized mucosa | 6.5 millimeters | Standard Deviation 2.1 |
| Ex Vivo Produced Oral Mucosa Equivalent | Clinical Increase in Zone (Width) of Keratinized Mucosa at Grafted Site | 4 week increase in keratinized mucosa | 4.5 millimeters | Standard Deviation 2.1 |
Secondary
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.
Time frame: 2, 4, 8 and 24 weeks after surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Palatal Oral Mucosa (POM) Graft | Graft Contracture | 8 weeks post surgery | 45 Percentage of graft contracture | Standard Deviation 11 |
| Palatal Oral Mucosa (POM) Graft | Graft Contracture | 2 weeks post surgery | 10 Percentage of graft contracture | Standard Deviation 28 |
| Palatal Oral Mucosa (POM) Graft | Graft Contracture | 24 weeks post surgery | 42 Percentage of graft contracture | Standard Deviation 15 |
| Palatal Oral Mucosa (POM) Graft | Graft Contracture | 4 weeks post surgery | 31 Percentage of graft contracture | Standard Deviation 24 |
| Ex Vivo Produced Oral Mucosa Equivalent | Graft Contracture | 24 weeks post surgery | 71 Percentage of graft contracture | Standard Deviation 6 |
| Ex Vivo Produced Oral Mucosa Equivalent | Graft Contracture | 2 weeks post surgery | 24 Percentage of graft contracture | Standard Deviation 34 |
| Ex Vivo Produced Oral Mucosa Equivalent | Graft Contracture | 8 weeks post surgery | 73 Percentage of graft contracture | Standard Deviation 4 |
| Ex Vivo Produced Oral Mucosa Equivalent | Graft Contracture | 4 weeks post surgery | 49 Percentage of graft contracture | Standard Deviation 13 |
Other Pre-specified
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.
Time frame: 2 and 4 weeks after surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Palatal Oral Mucosa (POM) Graft | Graft Blood Flow | 2 Week post surgery percent of perfusion units at graft site vs contralateral site on same subject | 202 Percent perfusion units graft/contralat | Standard Deviation 391 |
| Palatal Oral Mucosa (POM) Graft | Graft Blood Flow | 4 week post surgery percent of perfusion units at graft site vs contralateral site on same subject | 206 Percent perfusion units graft/contralat | Standard Deviation 234 |
| Ex Vivo Produced Oral Mucosa Equivalent | Graft Blood Flow | 2 Week post surgery percent of perfusion units at graft site vs contralateral site on same subject | 30 Percent perfusion units graft/contralat | Standard Deviation 4 |
| Ex Vivo Produced Oral Mucosa Equivalent | Graft Blood Flow | 4 week post surgery percent of perfusion units at graft site vs contralateral site on same subject | 222 Percent perfusion units graft/contralat | Standard Deviation 210 |
Other Pre-specified
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.
Time frame: 4 weeks after graft surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Palatal Oral Mucosa (POM) Graft | Immunohistochemistry Using Anti-CD31 (Cluster of Differentiation 31) to Detect Blood Vessel Growth Into the Graft. | 15 Number of blood vessels | Standard Deviation 5 |
| Ex Vivo Produced Oral Mucosa Equivalent | Immunohistochemistry Using Anti-CD31 (Cluster of Differentiation 31) to Detect Blood Vessel Growth Into the Graft. | 17 Number of blood vessels | Standard Deviation 7 |