Effectiveness of Adipose Tissue Derived Mesenchymal Stem Cells as Osteogenic Component in Composite Grafts (ROBUST)
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|ClinicalTrials.gov Identifier: NCT01532076|
Recruitment Status : Terminated (Slow recruitment)
First Posted : February 13, 2012
Last Update Posted : September 17, 2014
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|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||8 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|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|
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
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
- 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
- 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.
- 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.
- 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.
- 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
- 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
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 ClinicalTrials.gov identifier (NCT number): NCT01532076
|University Hospital Basel|
|Basel, Basel-Stadt, Switzerland, 4031|
|Principal Investigator:||Franziska Saxer, MD||University Hospital, Basel, Switzerland|
|Principal Investigator:||Marcel Jakob, MD||University Hospital, Basel, Switzerland|