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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01532076
Recruitment Status : Terminated (Slow recruitment)
First Posted : February 13, 2012
Last Update Posted : September 17, 2014
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Brief Summary:

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 or disease Intervention/treatment Phase
Osteoporotic Fractures Procedure: Cellularized composite graft augmentation Procedure: Acellular composite graft augmentation Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (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
Study Start Date : June 2012
Actual Primary Completion Date : September 2014
Actual Study Completion Date : September 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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
open reduction internal fixation (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

Primary Outcome Measures :
  1. Development of secondary dislocation within 12 months postoperative [ Time Frame: 12 months postoperative ]

    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 :
  1. Functional outcome 6 weeks, 6 and 12 months after fixation [ Time Frame: 12 months postoperative ]
    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.

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

  3. bone mineral density [ Time Frame: 12 months postoperative ]
    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.

  4. Histology [ Time Frame: 12 months postoperative ]
    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

  5. Dose-response [ Time Frame: 12 months postoperative ]
    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

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   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 mini mental Status (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
  • Known hypersensitivity to one of the graft components
  • Participation in a clinical trial within 3 month before enrolment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01532076

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University Hospital Basel
Basel, Basel-Stadt, Switzerland, 4031
Sponsors and Collaborators
University Hospital, Basel, Switzerland
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Principal Investigator: Franziska Saxer, MD University Hospital, Basel, Switzerland
Principal Investigator: Marcel Jakob, MD University Hospital, Basel, Switzerland

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Responsible Party: University Hospital, Basel, Switzerland Identifier: NCT01532076     History of Changes
Other Study ID Numbers: 348/10
First Posted: February 13, 2012    Key Record Dates
Last Update Posted: September 17, 2014
Last Verified: September 2014

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

Additional relevant MeSH terms:
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Fractures, Bone
Humeral Fractures
Osteoporotic Fractures
Wounds and Injuries
Arm Injuries
Fibrin Tissue Adhesive