Cell Therapy for Craniofacial Bone Defects

Study Overview
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Brief Summary
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The purpose of this research is to determine if a patient's own bone marrow tissue can help regenerate bone in the area of the jaw where an implant will be placed. The name of the process is called Bone Repair Cell (BRC) Therapy. A sample of bone marrow tissue will be collected and sent to a laboratory where it will be processed to form more cells. These new cells will then be transplanted in the regenerative site. The researchers are testing to see if these cells (BRC) will help form bone. The research will also determine if the implant will be more stable in the area with new bone growth.

Detailed Description
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Up to 20 (twenty) subjects who have alveolar defects secondary to clefts (n=10) or trauma (n=10), will be selected to participate in this study. Among the 20 patients, a total of up to 60 defect sites will be evaluated for bone regeneration following therapy, with each subject being evaluated in from one to four sites. Once enrolled, subjects from each of the two groups (cleft or trauma) will be randomly assigned to receive one of two possible treatments, traditional autogenous bone grafting or cell therapy (ixmyelocel-T)

Official Title
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Cell Therapy for Craniofacial Bone Defects

Conditions
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Cleft Palate, Trauma

Intervention / Treatment
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* Biological: Ixmyelocel-T
* Procedure: Autogenous Bone Grafting


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age range: 18 to 60 yrs 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 for Missing tooth criteria: Patients missing at least one maxillary lateral incisor secondary to cleft lip and/or palate: with compromised bone support for installation of dental implant(s) ( > 3 mm deficiency in horizontal and/or vertical bone height) with adequate interdental arch space for dental implant restorations with bony continuity between cleft segments with adequate interproximal space (between adjacent teeth) for dental implant installation Patients missing multiple (1-4 teeth) teeth secondary to trauma: in maxillary or mandibular anterior segments (second premolar to second premolar) with compromised bone support for installation of dental implant(s) ( > 3 mm deficiency in horizontal and/or vertical bone height) with adequate interdental arch space for dental implant restorations Exclusion Criteria: Allergies or hypersensitivities to study related medications: dexamethasone, chlorhexidine, ibuprofen. For patients allergic to amoxicillin a comparable substitute antibiotic will be used. Hematologic disorders/ blood dyscrasias. Patients will have blood drawn for a complete blood count (CBC) test. Current University of Michigan Health System normal lab values are as follows: white blood count (WBC: 4.0-10.0 x103/cmm), red blood count (RBC: male 4.50-5.90 x103/cmm; female 3.90-5.30x103/cmm), hemoglobin (HgB: male 13-17.3gm/dl; female 12-16gm/dl), Hct (male 39-50.2%; female 35-48%), mean corpuscular volume (MCV: 80-100fl), mean corpuscular hemoglobin (MCH: 25-35 pg), mean corpuscular hemoglobin concentration (MCHC: 30-37%), red cell distribution width (RDW: 11.5-15.5%), Plt (150-450x103/cmm). Active infectious disease Liver or kidney dysfunction/failure- Patients will have blood drawn for serum laboratory tests, including creatinine, blood urea nitrogen, aspartate aminotransferase test (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) blood urea nitrogen (BUN: 8-20 mg/dl) AST (8-30 IU/L) ALT (7-35 IU/L) Bilirubin (0.2-1.2 mg/dl). 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. Potential subjects whose laboratory values fall outside the UMHS normal ranges will be required to have medical clearance from their primary care provider prior to participation. Endocrine disorders/dysfunctions (i.e uncontrolled Type I or II diabetes, glycosylated hemoglobin [HA1C > 7%}) 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 standard deviation [SD]); Osteopenia = T score between -1.0 and -2.5 SD; Osteoporosis = T score at or below -2.5 SD. 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, 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 congenital or metabolic bone disorders Subjects with co-morbid conditions that would affect the study outcome or interpretation of study results will be excluded Subjects on significant concomitant drug therapy for systemic conditions (i.e. cardiovascular disease, renal dysfunction) will not be included in the study. Occasional short term use (7-14 days) of analgesics or common cold medication is permitted. Such use of these medications will be reviewed and recorded by the Investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Ixmyelocel-T<br>iliac bone marrow aspirates are expanded ex vivo to enrich for adult multipotent cells (ixmyelocel-T) capable of regenerating bone and blood vessels and reducing inflammation. Following cell expansion, autologous ixmyelocel-T is then packaged and can be used as an autologous graft for treatment of bone defects. | Biological: Ixmyelocel-T<br>* Twelve days after the bone marrow aspiration, alveolar grafting will be performed. Under local anesthesia, and possibly conscious intravenous sedation (depending on patient desire for sedation due to anxiety), alveolar grafting will be performed with the cell therapy (Ixmyelocel-T)<br>* Other names: bone repair cells;|
| Active Comparator: Autogenous Bone Grafting<br>Alveolar grafting will be performed. Under local anesthesia, and possibly conscious intravenous sedation (depending on patient desire for sedation due to anxiety), alveolar grafting will be performed with an autogenous bone block harvested from an intraoral or extraoral site, according to standard of care. | Procedure: Autogenous Bone Grafting<br>* Alveolar grafting will be performed. Under local anesthesia, and possibly conscious intravenous sedation (depending on patient desire for sedation due to anxiety), alveolar grafting will be performed with an autogenous bone block harvested from an intraoral or extraoral site, according to standard of care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Regeneration | The primary outcome variables for bone regeneration will be measured by histological and microcomputed tomographic (μCT) analyses at 4 months post-grafting. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Implant Stabilization | The ability of the dental implant fixtures to be loaded and remain stable for six months following implant loading (at 4 months) will be evaluated. | 10 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dental implants