Effectiveness of Adipose Tissue Derived Mesenchymal Stem Cells as Osteogenic Component in Composite Grafts

Official Title: “Effectiveness of Adipose Tissue Derived Mesenchymal Stem Cells as Osteogenic Component in Composite Grafts Versus Acellular Bone Graft Substitutes for Augmentation in the Treatment of Proximal Humeral Fractures as Model for Fractures of Osteoporotic Bone - a Prospective Randomized First in Men Proof of Principle Trial”

Failure rates of up to 30% are reported after proximal humeral fractures despite angular-stable devices. This may devastate not only the functional outcome but also the independence of elderly patients.

To increase bone mineral density and thereby holding-strength augmentation is an option.

Autologous bone-graft, as current gold-standard, though is questionable in osteoporosis since osteoprogenitors are dysfunctional and the harvesting-morbidity considerable. Adipose tissue seems an alternative cell-source even in presence of osteoporosis.

Stromal vascular fraction (SVF) cells isolated from lipoaspirates display osteogenic and vasculogenic potential and can be harvested in high numbers. Expansion associated with costly good-manufacturers-practice facilities is avoidable, so are repeated interventions.

These cells have been successfully used to generate osteogenic composite grafts with intrinsic vascularity in preclinical models.

For translation into clinical practice after a 20 patient external pilot a prospective randomized controlled trial with 270 patients is planned. For the trial lipoaspiration precedes open reduction and internal fixation in individuals over 60 years presenting with a proximal humeral fracture after low-energy trauma. Cells are isolated (Cellution®800/CRS) and wrapped around hydroxyapatite microgranules after embedding in a fibrin-gel for augmentation of the typical bone-void. Clinical/radiological follow-up is at 6 and 12 weeks for immediate complications and after 6, 9 and 12 months. Functional assessment is performed after 6 weeks, 6 and 12 months using the Quick-Dash- and Constant-Score.

The primary outcome is a reduction in secondary dislocation by 50% during the first postoperative year. Secondary dislocation is diagnosed on plain radiographs by an independent board certified radiologist specialised in musculoskeletal imaging if one or more of the following criteria are met: - More than 20° varus collapse of the humeral head fragment in relation to the humeral shaft - Screw penetration through the humeral head

Intervention(s) in this Clinical Trial

• Procedure: Cellularized composite graft augmentation
  • liposuction, cell isolation, embedding of SVF cells in fibrin gel, wrapping around hydroxyapatite granules
• Procedure: Acellular composite graft augmentation
  • Open reduction and internal fixation using acellular augmentation with fibrin embedded granulated hydroxyapatite

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: cellularized composite graft augmentation
  • lipoaspiration by experienced plastic surgeon, isolation of SVF cells using a Cellution/CR800® cell isolation device and single use kits (Cytori Therapeutics Inc., San Diego) during open reduction and internal fixation, augmentation of bone with cell-seeded bone graft substitute;
• Active Comparator: Control acellular composite graft augmentation
  • ORIF of the fracture, augmentation with acellular bone graft substitute.

Primary Measures

• Secondary dislocation within 12 months postoperative
  • Time Frame: 12 months postoperative
    Safety Issue?: No

Secondary Measures

• Functional outcome 6 weeks, 6 and 12 months after fixation
  • Time Frame: 12 months postoperative
    Safety Issue?: No
• Safety
  • Time Frame: 12 months postoperative
    Safety Issue?: Yes
• bone mineral density
  • Time Frame: 12 months postoperative
    Safety Issue?: No
• Histology
  • Time Frame: 12 months postoperative
    Safety Issue?: No
• Dose-response
  • Time Frame: 12 months postoperative
    Safety Issue?: No

Inclusion Criteria:

• Presentation with an isolated proximal humeral fracture after a low-energy trauma (e.g.
• falling from a standing position) and:
• indication for open reduction and internal fixation with a proximal humeral locking plate (PHILOS®, Synthes, Switzerland) after low energy trauma
• displacement of more than 1 cm between fragments and/or
• angulation of 45° or more between the fragments and/or
• dislocation of the greater tuberosity of 5 mm or more and/or
• patient specific factors like high functional demand etc
• age > 50 years
• postmenopausal status (i.e. 12 continuous month without menstruation)
• informed consent in surgery and study participation

Exclusion Criteria:

• Psychiatric disorder severely impairing co-operation (dementia MMS <24, schizophrenia, major depression)
• Pathological fractures caused by other conditions
• Fracture-related nerve injury
• Malignancies under current treatment (i.e. chemotherapy, radiotherapy etc.)
• BMI <20 kg/m2 or >30 kg/m2
• Known hypersensitivity to one of the graft components
• Participation in a clinical trial within 3 month before enrolment

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 50 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: University Hospital, Basel, Switzerland Other

Overall Clinical Trial Officials and Contacts

Franziska Saxer, MD Principal Investigator University Hospital, Basel, Switzerland  

Overall Contact: Franziska Saxer, MD 0041 61 328 saxerf@uhbs.ch

Information obtained from ClinicalTrials.gov on May 28, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01532076

Study ID Number: 348/10

ClinicalTrials.gov Identifier: NCT01532076

Health Authority: Switzerland: Federal Office of Public Health