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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by University Hospital, Basel, Switzerland
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:
NCT01532076
First received: January 5, 2012
Last updated: September 10, 2012
Last verified: September 2012
  Purpose

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

Condition Intervention Phase
Osteoporotic Fractures
Procedure: Cellularized composite graft augmentation
Procedure: Acellular composite graft augmentation
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University Hospital, Basel, Switzerland:

Primary Outcome Measures:
  • Development of secondary dislocation within 12 months postoperative [ Time Frame: 12 months postoperative ] [ Designated as safety issue: No ]

    Secondary dislocation within the first year postoperative on plain radiographs in ap. and Neer projections diagnosed by an independent radiologist specialized in musculoskeletal imaging in case of

    • more than 20° varus collapse of the humeral head fragment in relation to the humeral shaft
    • screw penetration through the humeral head


Secondary Outcome Measures:
  • Functional outcome 6 weeks, 6 and 12 months after fixation [ Time Frame: 12 months postoperative ] [ Designated as safety issue: No ]
    Functional outcome 6 weeks, 6 and 12 months after fixation: the functional outcome will be recorded by the Quick Dash Score and the Constant at each follow up visit and compared between the two groups. Additionally, pain at either surgical site will be recorded via the visual analogue scale.

  • Safety [ Time Frame: 12 months postoperative ] [ Designated as safety issue: Yes ]
    safety: all adverse reactions will be recorded and analysed to assess the safety of the approach in a typical patient population.

  • bone mineral density [ Time Frame: 12 months postoperative ] [ Designated as safety issue: No ]
    bone mineral density: in case of implant removal (see below) a 100 mm3 bone biopsy will be taken from the grafted area and analysed with MicroCT (micro computed tomography) for bone mineral density.

  • Histology [ Time Frame: 12 months postoperative ] [ Designated as safety issue: No ]
    histological assessment of qualitative and quantitative bone formation: bone biopsies will - after MicroCT assessment - be decalcified and histologically analysed using standard techniques and image quantification

  • Dose-response [ Time Frame: 12 months postoperative ] [ Designated as safety issue: No ]
    establishment of a dose response relationship between number of implanted cells an bone quantity in microCT and histologically via image quantification: retrospectively the quantitative measures of bone formation will be correlated to the number of implanted cells and their clonogenicity


Estimated Enrollment: 290
Study Start Date: June 2012
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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;
Procedure: Cellularized composite graft augmentation
liposuction, cell isolation, embedding of SVF cells in fibrin gel, wrapping around hydroxyapatite granules
Other Names:
  • Cellution/CR800, Cytori, US
  • Tisseel, Baxter, Germany
  • Actifuse Microgranules, Apatech, Germany
Active Comparator: Control acellular composite graft augmentation
ORIF of the fracture, augmentation with acellular bone graft substitute.
Procedure: Acellular composite graft augmentation
Open reduction and internal fixation using acellular augmentation with fibrin embedded granulated hydroxyapatite
Other Names:
  • Tisseel, Baxter, Germany
  • Actifuse Microgranules, Apatech, Germany

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01532076

Contacts
Contact: Franziska Saxer, MD 0041 61 328 ext 61 47 saxerf@uhbs.ch
Contact: Marcel Jakob, MD 0041 61 328 ext 70 04 jakobm@uhbs.ch

Locations
Switzerland
University Hospital Basel Recruiting
Basel, Basel-Stadt, Switzerland, 4031
Contact: Franziska Saxer, MD    0041 61 328 ext 61 47    saxerf@uhbs.ch   
Contact: Marcel Jakob, MD    0041 61 328 ext 70 04    jakobm@uhbs.ch   
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
Principal Investigator: Franziska Saxer, MD University Hospital, Basel, Switzerland
Principal Investigator: Marcel Jakob, MD University Hospital, Basel, Switzerland
  More Information

No publications provided

Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT01532076     History of Changes
Other Study ID Numbers: 348/10
Study First Received: January 5, 2012
Last Updated: September 10, 2012
Health Authority: Switzerland: Federal Office of Public Health

Keywords provided by University Hospital, Basel, Switzerland:
osteoporosis
prox. humeral fracture
geriatric trauma
mesenchymal stem cells

Additional relevant MeSH terms:
Fractures, Bone
Humeral Fractures
Shoulder Fractures
Osteoporotic Fractures
Wounds and Injuries
Arm Injuries

ClinicalTrials.gov processed this record on July 22, 2014