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

• Sponsor: University of Michigan (Other)
• Overall Status: Completed
• CT.gov ID: NCT00980278
• Collaborator: (none)
• Enrollment: 26
• Location: 1
• Arms: 2
• Duration (Months): 40
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Tooth Loss	Procedure: Sinus lift augmentation and dental implant; Biological: Aastrom BRCs	Phase 1/Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Cell Therapy Using Autologous Bone Marrow Cells Expanded Ex Vivo and Delivered Using Tricalcium Phosphate
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Jul 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. Bone Mineral Density of Bone Core [4 months]

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

2. Bone Volume Fraction of Bone Core [4 months]

   Bone volume fraction of bone core histological and µCT analyses

Secondary Outcome Measures

1. Change in Linear Radiographic Bone Height [Screening and 1 week post-op from baseline]

   Change in linear radiographic bone heights were measured before and after bone graft reconstruction

2. Change in Sinus Bone Volume [Pre-baseline and within 2 weeks of 4 Month visit]

   CBCT was used to evaluated 3-D changes in the bone volume within the treated areas of the sinus cavity

3. Final Bone Volume: Initial Graft Volume Ratio [4 months]

   Bone volume fraction of bone core histological and µCT analyses

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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

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

• 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

• 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 and are considered clinically significant will be required to have medical clearance from their primary care provider prior to participation. Potential subjects presenting with clinically insignificant laboratory abnormalities will not require medical clearance and will be considered for inclusion 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

• Long term (>2 weeks) use of antibiotics in the past 3 months

• Periodontally unstable subjects

• Subjects having any extractions in the possible treatment area in the past 3 months

• Subjects that are edentulous

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Michigan Clinical Research Database homepage

Publications

• Albrektsson T, Brånemark PI, Hansson HA, Lindström 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.
• Amler MH. The time sequence of tissue regeneration in human extraction wounds. Oral Surg Oral Med Oral Pathol. 1969 Mar;27(3):309-18.
• Atwood DA, Coy WA. Clinical, cephalometric, and densitometric study of reduction of residual ridges. J Prosthet Dent. 1971 Sep;26(3):280-95.
• 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.
• 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.
• 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.
• Kaigler D, Mooney D. Tissue engineering's impact on dentistry. J Dent Educ. 2001 May;65(5):456-62. Review.
• 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. Review.
• 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. Epub 2006 Jun 8.
• 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.
• 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.

• Responsible Party: William Giannobile, Principal Investigator, University of Michigan
• ClinicalTrials.gov Identifier: NCT00980278
• Other Study ID Numbers: HUM00014299
• First Posted: Sep 21, 2009
• Last Update Posted: Dec 23, 2015
• Last Verified: Nov 1, 2015

• Keywords provided by William Giannobile, Principal Investigator, University of Michigan: sinus lift; tooth extraction; dental implant
• Additional relevant MeSH terms: Tooth Loss

Study Results

Participant Flow

Arm/Group Title	Sinus Lift Plus Dental Implant	Sinus Lift Plus BRCs and Dental Implant
Arm/Group Description	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 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.	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 Aastrom BRCs: sinus augmentation, BRC application, dental implant
Period Title: Overall Study
STARTED	13	13
COMPLETED	11	13
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Sinus Lift Plus Dental Implant	Sinus Lift Plus BRCs and Dental Implant	Total
Arm/Group Description	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 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.	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 Aastrom BRCs: sinus augmentation, BRC application, dental implant	Total of all reporting groups
Overall Participants	13	13	26
Age, Customized (participants) [Number]
>20 and <70	13 100%	13 100%	26 100%
Sex: Female, Male (Count of Participants)
Female	10 76.9%	10 76.9%	20 76.9%
Male	3 23.1%	3 23.1%	6 23.1%
Region of Enrollment (participants) [Number]
United States	13 100%	13 100%	26 100%

Outcome Measures

1. Primary Outcome

Title	Bone Mineral Density of Bone Core
Description	Bone mineral density of bone core was measured by histological and µCT analyses
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sinus Lift Plus Dental Implant	Sinus Lift Plus BRCs and Dental Implant
Arm/Group Description	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 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.	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 Aastrom BRCs: sinus augmentation, BRC application, dental implant
Measure Participants	11	13
Mean (Standard Deviation) [mg/mm^3]	.79 (.05)	.78 (.02)

2. Secondary Outcome

Title	Change in Linear Radiographic Bone Height
Description	Change in linear radiographic bone heights were measured before and after bone graft reconstruction
Time Frame	Screening and 1 week post-op from baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sinus Lift Plus Dental Implant	Sinus Lift Plus BRCs and Dental Implant
Arm/Group Description	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 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.	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 Aastrom BRCs: sinus augmentation, BRC application, dental implant
Measure Participants	11	13
Mean (Standard Deviation) [mm]	12.8 (2.8)	12.2 (3.3)

3. Primary Outcome

Title	Bone Volume Fraction of Bone Core
Description	Bone volume fraction of bone core histological and µCT analyses
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sinus Lift Plus Dental Implant	Sinus Lift Plus BRCs and Dental Implant
Arm/Group Description	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 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.	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 Aastrom BRCs: sinus augmentation, BRC application, dental implant
Measure Participants	11	13
Mean (Standard Deviation) [ratio]	.43 (8.1)	.49 (7.2)

4. Secondary Outcome

Title	Change in Sinus Bone Volume
Description	CBCT was used to evaluated 3-D changes in the bone volume within the treated areas of the sinus cavity
Time Frame	Pre-baseline and within 2 weeks of 4 Month visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sinus Lift Plus Dental Implant	Sinus Lift Plus BRCs and Dental Implant
Arm/Group Description	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 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.	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 Aastrom BRCs: sinus augmentation, BRC application, dental implant
Measure Participants	11	13
Mean (Standard Deviation) [cm3]	2.1 (.9)	1.8 (1.0)

5. Secondary Outcome

Title	Final Bone Volume: Initial Graft Volume Ratio
Description	Bone volume fraction of bone core histological and µCT analyses
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sinus Lift Plus Dental Implant	Sinus Lift Plus BRCs and Dental Implant
Arm/Group Description	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 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.	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 Aastrom BRCs: sinus augmentation, BRC application, dental implant
Measure Participants	11	13
Mean (Standard Deviation) [ratio]	.64 (.2)	.51 (.3)

Adverse Events

Time Frame	4 years
Arm/Group Title	Sinus Lift Plus Dental Implant		Sinus Lift Plus BRCs and Dental Implant
Arm/Group Description	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 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.		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 Aastrom BRCs: sinus augmentation, BRC application, dental implant
All Cause Mortality
	Sinus Lift Plus Dental Implant		Sinus Lift Plus BRCs and Dental Implant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sinus Lift Plus Dental Implant		Sinus Lift Plus BRCs and Dental Implant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/13 (7.7%)		1/13 (7.7%)
Infections and infestations
Sinus	0/13 (0%)	0	1/13 (7.7%)	13
Surgical and medical procedures
Surgery	1/13 (7.7%)	13	0/13 (0%)	0
Other (Not Including Serious) Adverse Events
	Sinus Lift Plus Dental Implant		Sinus Lift Plus BRCs and Dental Implant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/13 (69.2%)		9/13 (69.2%)
Gastrointestinal disorders
Vomitting	1/13 (7.7%)	1	2/13 (15.4%)	2
General disorders
Lesion	1/13 (7.7%)	1	0/13 (0%)	0
Bleeding	1/13 (7.7%)	1	0/13 (0%)	0
Broken Tooth	2/13 (15.4%)	2	0/13 (0%)	0
Suture Loss	0/13 (0%)	0	1/13 (7.7%)	1
Pain and Swelling	0/13 (0%)	0	2/13 (15.4%)	2
Flap Mobility	1/13 (7.7%)	1	0/13 (0%)	0
Sore Throat	0/13 (0%)	0	1/13 (7.7%)	1
Non-restoreable Tooth	0/13 (0%)	0	1/13 (7.7%)	1
Headaches	0/13 (0%)	0	1/13 (7.7%)	1
Oral Ulcer	1/13 (7.7%)	1	0/13 (0%)	0
Tingling	0/13 (0%)	0	1/13 (7.7%)	1
Lack of Bone	1/13 (7.7%)	1	1/13 (7.7%)	1
Rash	1/13 (7.7%)	1	0/13 (0%)	0
Pain	2/13 (15.4%)	2	1/13 (7.7%)	1
Discomfort	0/13 (0%)	0	1/13 (7.7%)	1
Prosthesis Came Off	6/13 (46.2%)	6	2/13 (15.4%)	2
Sensitivity	0/13 (0%)	0	1/13 (7.7%)	1
Bleeding	0/13 (0%)	0	1/13 (7.7%)	1
Tenderness	0/13 (0%)	0	1/13 (7.7%)	1
Ovarian Ulcer Rupture	1/13 (7.7%)	1	0/13 (0%)	0
Infections and infestations
Infection	1/13 (7.7%)	1	0/13 (0%)	0
Injury, poisoning and procedural complications
Soft Tissue Opening	2/13 (15.4%)	2	0/13 (0%)	0
Injury	0/13 (0%)	0	3/13 (23.1%)	3
Swelling	0/13 (0%)	0	1/13 (7.7%)	1
Exostosis	0/13 (0%)	0	1/13 (7.7%)	1
Perforations	0/13 (0%)	0	1/13 (7.7%)	1
Skin and subcutaneous tissue disorders
Shingles	1/13 (7.7%)	1	0/13 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.