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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 8
- 试验地点
- 2
- 主要终点
- Development of secondary dislocation within 12 months postoperative
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Development of secondary dislocation within 12 months postoperative
时间窗: 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
次要结局
- Safety(12 months postoperative)
- bone mineral density(12 months postoperative)
- Histology(12 months postoperative)
- Dose-response(12 months postoperative)
- Functional outcome 6 weeks, 6 and 12 months after fixation(12 months postoperative)