Autologous BM-MSC Transplantation in Combination With Platelet Lysate (PL) for Nonunion Treatment

Study Overview
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Brief Summary
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Nonunion of long bones would occur in almost 10% of fractures and because of its long term and complicated treatment, is known as a therapeutic challenge for both of the surgeons and patients. Cell therapy is useful in treatment of nonunion and mesenchymal stromal/stem cells are the best candidates for this kind of treatment. Percutaneous implantation of autologous bone marrow derived mesenchymal stromal/stem cell in combination with PL will be done in 30 patients with tibia nonunion. The other 30 patients as the control group will receive placebo. The patients will be followed at 2weeks, 3months, 6m and 12 months after implantation. The Spss(v16) software will be used for data analysis.

Detailed Description
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Long bone nonunion is known as a therapeutic challenge for both the orthopedic surgeons and the society. Current treatment of this disorder is autologous bone graft. This treatment has potential minor and major complications and is considered as a risky treatment. So researches are focused on new treatment approaches for this disease. Cell therapy is one of these new approaches especially based on mesenchymal stromal cells. The investigators will evaluate safety and efficacy of percutaneous implantation of autologous BM-MSC (bone marrow -derived mesenchymal stromal cell) in combination with PL (platelet lysate product) in 30 tibia nonunion patients. The other 30 patients will receive placebo. These patients will be followed up and data will be analyzed with spss(v16).

Official Title
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Use of Autologous Bone Marrow Derived Mesenchymal Stromal Cells in Combination With Platelet Lysate Product for Human Long Bone Nonunion Treatment, A Phase 2-3 Clinical Trial

Conditions
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Bone Fracture

Intervention / Treatment
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* Biological: Percutaneous injection
* Other: Percutaneous injection


Participation Criteria
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Eligibility Criteria
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inclusion criteria: Non-united fracture of tibial midshaft at X-ray. Non-united gap less than 1cm. Fracture has fixed by closed intramedullary rod. Hypotrophic type. At least 6 months after initial surgery. Patient informed consent. Exclusion criteria: Infected nonunion Multiple major fracture Non treated major fracture malignancy Pregnancy or lactating Uncontrolled chronic diseases, such as: diabetes mellitus, hypertension, renal diseases, liver diseases, thyroid diseases, heart diseases, blood diseases, etc. Steroid usage. Positive test for HIV and/or HBS and/or HBC and/or HTLV (1,2) Fracture site more than 1 cm.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSC recipients<br>The patients with nonunion fracture who underwent percutaneous implantation of bone marrow derived mesenchymal stem cells in combination with platelet lysate product. | Biological: Percutaneous injection<br>* percutanous implantation of bone marrow derived mesenchymal stromal cells in patients with nonunion fracture.<br>|
| Placebo Comparator: Placebo<br>The patients with nonunion fracture who underwent percutaneous injection of placebo. | Other: Percutaneous injection<br>* Percutaneous implantation of placebo in patients with nonunion fracture.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical union | - Clinical union is defined as an asymptomatic patient who was able to fully bear weight on the injured leg | 3months | 
| Radiological healing | - radiographic fracture healing is defined by bone continuity (bony bridging) present in three out of four cortices in two projections (anterior-posterior & lateral x-rays), assessed by a blinded senior orthopedic surgeon. CT scan, for confirm the results - radiolographic fracture healing is defined by bone continuity (bony bridging) present in three out of four cortices in two projections (anterior-posterior & lateral x-rays), assessed by a blinded senior orthopedic surgeon. CT scan, for confirm the results - radiolographic fracture healing is defined by bone continuity (bony bridging) present in three out of four cortices in two projections (anterior-posterior & lateral x-rays), assessed by a blinded senior orthopedic surgeon. CT scan, for confirm the results | 1week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain | The pain relief as measured by Visual Analogue Scale (VAS) 3 months after cell injection | 3months | 
| Quality of life | Evaluation the patients' quality of life with Visual Analogue Score (VAS) 3months after cell transplantation. | 3months | 
| Walking distance | Walking distance changes as measured by walking on treadmill 3 months after cell injection. | 3months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autologous, nonunion fracture, bone marrow, mesenchymal, stromal cell, platelet lysate product