Treatment of Alveolar Bone Defects Using Aastrom Biosciences Autologous Tissue Repair Cell Therapy

Study Overview
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Brief Summary
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The purpose of this research is to determine if a subject's own bone marrow tissue can help regenerate bone in the area of his/her jaw where a tooth has been removed using Tissue Repair Cell (TRC) Therapy.

Detailed Description
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A sample of the subject's bone marrow tissue will be collected and sent to a laboratory where it will be processed to form cells. The new cells are transplanted into the tooth socket after the tooth has been removed. The researchers are testing to see if these cells (TRC) will help form bone. The research will also determine if the implant the subject receives will be more stable in the area with new bone growth.

Official Title
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Treatment of Alveolar Bone Defects Using Aastrom Biosciences Autologous Tissue Repair Cell Therapy

Conditions
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Alveolar Bone Loss

Intervention / Treatment
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* Biological: Tissue Repair Cells (TRC)
* Device: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age range: 20 to 70 years Gender: Male and female Patients must be able and willing to follow study procedures and instructions Patients must have read, understood and signed an informed consent form Patients must require tooth extraction as a result of caries, periodontal disease, or tooth fracture Exclusion Criteria: Allergies or hypersensitivities to study related medications: amoxicillin, dexamethasone, chlorhexidine, ibuprofen, ranitidine Hematologic disorders/ blood dyscrasias Active infectious disease Liver or kidney dysfunction/failure- Patients will have blood drawn for serum laboratory tests, including creatinine, blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase test (ALT), and bilirubin. All of these must be within normal limits for a patient to be included in the study. Current University of Michigan Health System normal lab values are as follows: Creatinine (male 0.7-1.3 mg/dl; female 0.5-1.0 mg/dl); BUN (8-20 mg/dl); AST (8-30 IU/L); ALT (7-35 IU/L); Bilirubin (0.2-1.2 mg/dl). Endocrine disorders/dysfunctions (i.e Type I and II diabetes) Cancer - The explicit definition of cancer used to exclude patients is consistent with that described by the National Cancer Institute (NCI), National Institutes of Health. According to NCI, cancer is any disease in which abnormal cells divide without control and invade nearby tissues (invasive disease). These include carcinomas, sarcomas, leukemias, and lymphomas. Any patient with a history of these invasive diseases will be excluded from the study. Patients who currently use bisphosphonates or have a history of bisphosphonate use will be excluded from the trial. HIV+ Metabolic Bone Diseases-Patients with metabolic bone diseases such as Paget's disease, hypercalcemia, moderate to severe vitamin D3 abnormalities or any other metabolic bone disease including osteoporosis and osteoporotic fractures will be excluded. The following scale will be used to determine osteoporosis in patients who have had a bone mass density (BMD) determination: Normal = T score at or above -1.0 SD; Osteopenia = T score between -1.0 and -2.5 SD; Osteoporosis = T score at or below -2.5 standard deviation (SD). Although a dexa scan will not be required, all post-menopausal women receiving osteoporosis/osteopenia related therapy will receive a dexa scan as part of their standard medical care. Additionally, individuals who have a medical history significant for diabetes will not be included in the study. Laboratory values that will define normal renal and hepatic function, as well as criteria for exclusion of metabolic bone disease are consistent with those established by the University of Michigan Health System (UMHS). Normal clinical values will be used to help assure the health of all subjects in this trial. Individuals who have a BMI outside normal limits or a BMI that deems them overweight (BMI >25) will be excluded due to potential difficulties in locating appropriate surgical entry of the iliac crest during bone marrow aspiration procedure. The following additional exclusion criteria for regenerative sites are in alignment with those described and adapted for using bone morphogenetic protein (BMPs) to regenerate buccal wall defects (Fiorellini, Howell et al. 2005): Patients < 20 and > 60 years of age Pregnant women- Female patients who are of childbearing potential are excluded except those who are using hormonal or barrier methods of birth control (oral or parenteral contraceptives, transdermal patch, diaphragm plus spermicide, or condoms). Pregnancy status will be determined with a urine test and patients who are pregnant, as determined by a positive test, will be excluded from the study Patients with acute sinusitis Patients with congenital or metabolic bone disorders Current smokers (have smoked within 6 mos. of study onset) Presence of < 4 mm of bone from apex of tooth to the alveolar crest < 2 mm bone from apex to floor of maxillary sinus

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 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 |
| --- | --- |
| Experimental: Tissue Repair Cells (TRC)<br>Subjects will receive Tissue Repair Cell (TRC) therapy plus Gelfoam carrier | Biological: Tissue Repair Cells (TRC)<br>* 30-50 ml of bone marrow is aspirated from subject and processed into TRC autologous bone marrow tissue graft. 10ml of TRC will be absorbed onto gelfoam carrier and placed in extraction socket.<br>* Other names: Tissue Repair Cells, Bone Repair Cells, ixmyelocel-t;Device: Control<br>* Control subjects only receive standard gelfoam carrier. It promotes healing after tooth extraction<br>* Other names: Gelfoam;|
| Sham Comparator: Control<br>Subjects will receive the control treatment, consisting of Gelfoam carrier without Tissue Repair Cell (TRC) therapy. | Device: Control<br>* Control subjects only receive standard gelfoam carrier. It promotes healing after tooth extraction<br>* Other names: Gelfoam;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Regeneration | The primary objective of this study is to determine whether the placement of Tissue Repair Cells (TRCs) at the time of tooth extraction can safely and effectively promote bone regeneration in alveolar bone defects created by tooth extraction. Safety was assessed through adverse event reporting Bone regeneration was assessed through measures of bone mineral density and bone volume fraction of biopsied regenerated bone tissue. Bone regeneration was also measured through radiographic analysis of relative bone height gain (% of the bone height regenerated relative to the height before tooth extraction) | 12 months after tooth extraction | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Successfully Received Dental Implant Fixtures | The secondary objective is to determine if Tissue Repair Cell therapy regenerates bone enabling the installation and stability of dental implant fixtures | 12 months after tooth extraction | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dental, tooth, implant, extraction, Oral, Surgical, Procedures