Bone Tissue Engineering Using Autologous Bone Repair Cell (BRC) Therapy for Sinus Floor Bone Augmentation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
William Giannobile, University of Michigan
ClinicalTrials.gov Identifier:
NCT00980278
First received: September 18, 2009
Last updated: April 16, 2014
Last verified: March 2014
  Purpose

The purpose of this research is to determine if one's own bone marrow tissue can help regenerate (grow) 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 or sinus floor augmentation site. The researchers are testing to see if these cells (BRC) will help form bone indicating. The research will also determine if the implant will be more stable in the area with new bone growth.


Condition Intervention Phase
Tooth Loss
Procedure: Sinus lift augmentation and dental implant
Biological: Aastrom BRCs
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cell Therapy Using Autologous Bone Marrow Cells Expanded Ex Vivo and Delivered Using Tricalcium Phosphate

Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • The primary objective of this study is to determine whether the placement of BRC during bone regenerative sinus augmentation can safely and effectively promote bone regeneration in the resorbed posterior maxilla. [ Time Frame: 16 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The secondary objective is to determine if BRC therapy regenerates bone, following sinus augmentation, sufficient to enable the installation and stability of dental implant fixtures. [ Time Frame: 16 months ] [ Designated as safety issue: Yes ]

Enrollment: 22
Study Start Date: March 2010
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: sinus lift plus dental implant

Transalveolar sinus augmentation will be performed. After 4 months dental implants will be delivered only if primary stability can be achieved.

Intervention (Procedure/Surgery): Sinus lift augmentation and dental implant transalveolar sinus augmentation will be performed. After 4 months, dental implants will be delivered only if primary stability can be achieved.

Biological/Vaccine: N/A; only sinus augmentation and dental implant

Procedure: Sinus lift augmentation and dental implant
transalveolar sinus augmentation will be performed. After 4 months, dental implants will be delivered only if primary stability can be achieved.
Experimental: sinus lift plus BRCs and dental implant

transalveolar sinus augmentation will be performed. A unit dose of BRC (10 ml) will be mixed with a commercially available β-TCP (Cerasorb), which will be used as a carrier to deliver the cells.

Intervention (Procedure/Surgery): Sinus lift augmentation and dental implant transalveolar sinus augmentation will be performed. After 4 months, dental implants will be delivered only if primary stability can be achieved.

Biological/Vaccine: Aastrom BRCs, sinus augmentation, BRC application, dental implant

Biological: Aastrom BRCs
sinus augmentation, BRC application, dental implant

Detailed Description:

The overall aim is to promote bone regeneration, using Aastrom's proprietary Adult Stem Cell Therapy (AST) developed collaboratively with the University of Michigan, to enable placement of dental implants in patients who lack adequate alveolar bone. This project addresses specifically the placement of dental implants following bone regenerative sinus floor augmentation. This novel therapy mitigates the risks of other therapies, providing additional benefits of adequate cell numbers for high quality bone regeneration, and has the potential to become the new standard of care. In Aastrom's patented manufacturing technology, iliac bone marrow aspirates are expanded ex-vivo to enrich for adult multipotent cells (Bone Repair Cells- BRC) capable of regenerating bone and blood vessels. BRC will then be mixed with bone matrix graft extender, beta-tricalcium phosphate (β-TCP), before their implantation into the regenerative site.

  Eligibility

Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age range 20 to 70 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 form;
  • Patients must be requiring sinus augmentation to allow dental implant placement
  • Patients must be missing the following teeth: Maxillary second premolar, maxillary first molar and/or maxillary second molar.

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 cell count (WBC: 4.0-10.0 x103/cmm), red blood cell 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, 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 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 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 acute sinusitis
  • Patients with congenital or metabolic bone disorders
  • Current smokers (have smoked within 6 mos. of study onset)
  • Subjects with co-morbid conditions that would affect the study outcome or interpretation of study results will be excluded
  • Individuals who have a Body Mass Index, or BMI outside normal limits that deems them overweight (BMI >25) will be excluded due to potential difficulties in locating appropriate surgical entry of the iliac crest during the bone marrow aspiration procedure. (The BMI is a measure of your weight relative to your height and waist circumference, in an effort to measure abdominal fat.)
  • Subjects having any extractions in the possible treatment area in the past 3 months
  • Subjects that are completely edentulous
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00980278

Locations
United States, Michigan
Michigan Center for Oral Health Research
Ann Arbor, Michigan, United States, 48106
Sponsors and Collaborators
University of Michigan
Investigators
Principal Investigator: William Giannobile, DDS, DMedSc University of Michigan
  More Information

Additional Information:
Publications:

Responsible Party: William Giannobile, Principal Investigator, University of Michigan
ClinicalTrials.gov Identifier: NCT00980278     History of Changes
Other Study ID Numbers: 2009-01
Study First Received: September 18, 2009
Last Updated: April 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Michigan:
sinus lift
tooth extraction
dental implant

Additional relevant MeSH terms:
Tooth Loss
Mouth Diseases
Periodontal Diseases
Stomatognathic Diseases
Tooth Diseases

ClinicalTrials.gov processed this record on October 29, 2014