Treatment of Atrophic Nonunion Fractures by Autologous Mesenchymal Stem Cell Percutaneous Grafting. A Randomized, Double-blind, Controlled Study
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Proportion of patients receiving Mesenchymal Stem Cells that develop a partial or complete callus at 6 and 12 months, compared to patients receiving placebo.
研究概览
简要总结
Bone fractures heal most of the time particularly well and without complications. The solidification takes rarely more than two to three months. The wound healing depends greatly on a good blood supply and needs several steps. These processes culminate in a new mass of heterogeneous tissue which is known as the fracture callus. Unfortunately, 2%-5% bone fractures cannot achieve a proper solidification and between the ununited fragments a scar tissue appears. This incorrect healing induces pain and even infections. When this situation persists more than 6 months, it is referred to as nonunion fracture, which will require some form of intervention to stimulate the natural healing process of the body. First of all, good surgical techniques with stable immobilization should be applied and local infection should be excluded. Then stimulation of the callus is required. Cell therapy with bone marrow cells has emerged as a promising new approach for bone regeneration. Animal studies as well as preliminary human studies have shown that Mesenchymal Stem Cells, a particular kind of stem cells isolated from the bone marrow, could induce callus formation when injected in the nonunion site of a broken bone.
In this study the investigators aim at determining whether Mesenchymal Stem Cells (MSC) isolated from the patient's bone marrow and injected in the nonunion site could be a safe and effective treatment for nonunion fractures. Patients will be randomized in two groups; one injected with Mesenchymal Stem Cell and the other injected with placebo. The investigators seek also to know how long it takes to develop the callus formation and whether there is a partial or a complete callus formation.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female; female patients must use a reliable contraception method
- •Age ≥ 18 years
- •Fracture having no radiological callus after 6 months and absence of any hypertrophic bone reaction.
- •No sepsis
- •Good skin covering
- •Be able and willing to participate in the study
- •Written informed consent
排除标准
- •Evidence of malignancy (except non-melanoma skin cancer) in the past five years
- •Pregnancy or breastfeeding
- •Patient positive by serology or PCR for HIV, hepatitis B or C infection
- •Insufficient reduction of the fracture with displaced fragments
- •Evidence of local sepsis by clinical signs, biological parameters (CRP) and/or positive isotopic scan using Indium-labelled leucocytes
研究组 & 干预措施
Mesenchymal Stem Cells
2 ml with 40 X 10E6 Mesenchymal Stem Cells (MSC) will be injected in the nonunion space of the bone fracture.
MSC will be injected even if the number of available cells is lower than 40 X 10E6.
The injection of MSC in the nonunion space will be performed percutaneously using a 3-mm trephine needle under fluoroscopic control and loco-regional or general anesthesia, as deemed appropriate by the anesthetist.
干预措施: Mesenchymal Stem Cells (Biological)
结局指标
主要结局
Proportion of patients receiving Mesenchymal Stem Cells that develop a partial or complete callus at 6 and 12 months, compared to patients receiving placebo.
时间窗: 6 and 12 months
Radiological evaluation of the callus by standard X-rays and computed tomography (CT).
Safety of Mesenchymal Stem Cells injection in nonunion fractures.
时间窗: 12 months
Follow-up for revealing any significant immediate or late adverse effects.
次要结局
- Value of [18F]-NaF PET scans for early prediction of the onset of the bone healing process.(3 months)
- Timing of development of a partial or complete callus in the 2 groups.(12 months for one injection or 18 months when a second injection is needed)
- Proportion of patients receiving Mensechymal Stem Cells that develop a partial or complete callus at 2, 3, 4, 8 and 10 months, compared to patients receiving placebo(2, 3, 4, 8 and 10 months)
- Patient evaluation of pain and global satisfaction.(12 months)
- Proportion of patients achieving different degrees of functional success.(2, 3, 4, 6, 8, 10 and 12 months)
- Evaluation of early homing of Mesenchymal Stem Cells.(24 hours)
- Incidence of adverse events and severe adverse events in the 2 groups.(12 months for one injection and 18 months when a second injection is performed)