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

NCT00980278 | Completed Phase 1 Results DMC

• 1 other identifier: HUM00014299
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Tooth Loss

Keywords

sinus lift; tooth extraction; dental implant

Outcome Measures

Primary Outcomes (2)

• Bone Mineral Density of Bone Core

  Bone mineral density of bone core was measured by histological and µCT analyses

  4 months

• Bone Volume Fraction of Bone Core

  Bone volume fraction of bone core histological and µCT analyses

  4 months

Secondary Outcomes (3)

• Change in Linear Radiographic Bone Height

  Screening and 1 week post-op from baseline

• Change in Sinus Bone Volume

  Pre-baseline and within 2 weeks of 4 Month visit

• Final Bone Volume: Initial Graft Volume Ratio

  4 months

Study Arms (2)

sinus lift plus dental implant

ACTIVE COMPARATOR

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

sinus lift plus BRCs and dental implant

EXPERIMENTAL

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

Interventions

Sinus lift augmentation and dental implant PROCEDURE

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

sinus lift plus dental implant

Aastrom BRCs BIOLOGICAL

sinus augmentation, BRC application, dental implant

sinus lift plus BRCs and dental implant

Eligibility Criteria

• Age: 20 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age range: 20-70 yrs
• Gender: Male and female
• Systemically healthy: Physical status according to the American Society of Anesthesiologists (ASA) I or II
• Requiring sinus augmentation to allow dental implant placement
• Missing teeth: Maxillary second premolar, maxillary first molar and/or maxillary second molar
• Remaining alveolar bone height: 2 to 6 mm
• Must be able and willing to follow study procedures and instructions
• Must have read, understood and signed an informed consent form

You may not qualify if:

• 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
• Active infectious disease
• Liver or kidney dysfunction/failure- Patients will have blood drawn for serum laboratory tests, including creatinine, blood urea nitrogen, AST, ALT, and bilirubin. All of these must be within normal limits for a patient to be included in the study
• 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
• 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 will be excluded
• Patients with acute sinusitis, or presenting any sinus pathology that would contraindicate sinus augmentation
• Patients with congenital or metabolic bone disorders
• Current smokers (have smoked within 6 mos. of study onset)
• Subjects with congenital, or co-morbid conditions that would affect the study outcome or interpretation of study results will be excluded
• Individuals who have a 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

Sponsors & Collaborators

• University of Michigan: lead

Study Sites (1)

Michigan Center for Oral Health Research

Ann Arbor, Michigan, 48106, United States

Location

Related Publications (12)

• Albrektsson T, Branemark PI, Hansson HA, Lindstrom J. Osseointegrated titanium implants. Requirements for ensuring a long-lasting, direct bone-to-implant anchorage in man. Acta Orthop Scand. 1981;52(2):155-70. doi: 10.3109/17453678108991776.

  PMID: 7246093 BACKGROUND

• Amler MH. The time sequence of tissue regeneration in human extraction wounds. Oral Surg Oral Med Oral Pathol. 1969 Mar;27(3):309-18. doi: 10.1016/0030-4220(69)90357-0. No abstract available.

  PMID: 5251474 BACKGROUND

• Colter DC, Class R, DiGirolamo CM, Prockop DJ. Rapid expansion of recycling stem cells in cultures of plastic-adherent cells from human bone marrow. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3213-8. doi: 10.1073/pnas.97.7.3213.

  PMID: 10725391 BACKGROUND

• Krebsbach PH, Kuznetsov SA, Bianco P, Robey PG. Bone marrow stromal cells: characterization and clinical application. Crit Rev Oral Biol Med. 1999;10(2):165-81. doi: 10.1177/10454411990100020401.

  PMID: 10759420 BACKGROUND

• Kaigler D, Mooney D. Tissue engineering's impact on dentistry. J Dent Educ. 2001 May;65(5):456-62.

  PMID: 11425250 BACKGROUND

• Mankani MH, Kuznetsov SA, Wolfe RM, Marshall GW, Robey PG. In vivo bone formation by human bone marrow stromal cells: reconstruction of the mouse calvarium and mandible. Stem Cells. 2006 Sep;24(9):2140-9. doi: 10.1634/stemcells.2005-0567. Epub 2006 Jun 8.

  PMID: 16763200 BACKGROUND

• Marei MK, Nouh SR, Saad MM, Ismail NS. Preservation and regeneration of alveolar bone by tissue-engineered implants. Tissue Eng. 2005 May-Jun;11(5-6):751-67. doi: 10.1089/ten.2005.11.751.

  PMID: 15998216 BACKGROUND

• Nevins M, Giannobile WV, McGuire MK, Kao RT, Mellonig JT, Hinrichs JE, McAllister BS, Murphy KS, McClain PK, Nevins ML, Paquette DW, Han TJ, Reddy MS, Lavin PT, Genco RJ, Lynch SE. Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: results of a large multicenter randomized controlled trial. J Periodontol. 2005 Dec;76(12):2205-15. doi: 10.1902/jop.2005.76.12.2205.

  PMID: 16332231 BACKGROUND

• Atwood DA, Coy WA. Clinical, cephalometric, and densitometric study of reduction of residual ridges. J Prosthet Dent. 1971 Sep;26(3):280-95. doi: 10.1016/0022-3913(71)90070-9. No abstract available.

  PMID: 5284182 BACKGROUND

• Evian CI, Rosenberg ES, Coslet JG, Corn H. The osteogenic activity of bone removed from healing extraction sockets in humans. J Periodontol. 1982 Feb;53(2):81-5. doi: 10.1902/jop.1982.53.2.81.

  PMID: 6950085 BACKGROUND

• Friedenstein AJ, Ivanov-Smolenski AA, Chajlakjan RK, Gorskaya UF, Kuralesova AI, Latzinik NW, Gerasimow UW. Origin of bone marrow stromal mechanocytes in radiochimeras and heterotopic transplants. Exp Hematol. 1978 May;6(5):440-4.

  PMID: 350596 BACKGROUND

• Kaigler D, Avila-Ortiz G, Travan S, Taut AD, Padial-Molina M, Rudek I, Wang F, Lanis A, Giannobile WV. Bone Engineering of Maxillary Sinus Bone Deficiencies Using Enriched CD90+ Stem Cell Therapy: A Randomized Clinical Trial. J Bone Miner Res. 2015 Jul;30(7):1206-16. doi: 10.1002/jbmr.2464.

  PMID: 25652112 RESULT

MeSH Terms

Conditions

Tooth Loss

Interventions

Dental Implants

Condition Hierarchy (Ancestors)

Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases; Tooth Diseases

Intervention Hierarchy (Ancestors)

Dental Materials; Biomedical and Dental Materials; Dental Prosthesis; Prosthodontics; Dentistry; Prostheses and Implants; Equipment and Supplies; Manufactured Materials; Technology, Industry, and Agriculture

Results Point of Contact

• Title: Dr. William Giannobile, Chair Department of Periodontics and Oral Medicine
• Organization: University of Michigan School of Dentistry

wgiannob@umich.edu

734-763-2105

Study Officials

• William Giannobile, DDS, DMedSc

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 18, 2009
• First Posted: September 21, 2009
• Study Start: March 1, 2010
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: December 23, 2015
• Results First Posted: December 23, 2015

Record last verified: 2015-11

Locations

US (1)