Clinical Trial Based on the Use of Mononuclear Cells From Autologous Bone Marrow in Patients With Pseudoarthrosis

Study Overview
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Brief Summary
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The purpose of this clinical trial is to check the non-inferiority and lower morbidity of the use of bone marrow mononuclear cells seeded onto a porous matrix of calcium phosphate, for the consolidation of tibial bone defects (pseudoarthrosis), compared with autologous bone graft.

Detailed Description
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An estimated 10% of closed fractures and between 35-45% in cases of open fractures, are at risk of developing a delay in the process of consolidation or a complete failure of it (pseudoarthrosis) depending on location , severity of trauma on bone, soft tissue and vascular structures Some of these cases are refractory to all treatment methods available today, requiring numerous interventions with the potential risk for recurrent infections that they carry. For this reason, its treatment remains a challenge for the orthopedic surgeon. Recent advances in knowledge of cellular and molecular biology related to the mechanism of bone repair and biomaterials science have been joined in a new discipline called tissue engineering, its implementation in clinical practice is being done so progressive. Cell therapy based on the use of adult stem cells (MSCs) derived from autologous bone marrow, introduces new applications for the repair of fractures including pseudoarthrosis and avascular bone necrosis. Its mechanism of action does not focus only on their local action, but also in the release of signaling molecules with autocrine and paracrine action through recruitment and activation of endogenous MSCs to osteoblastic differentiation and bone tissue regeneration. On the other hand, the seeding of MSCs on biomaterials (natural or synthetic) is more effective, to facilitate adherence, proliferation and extracellular matrix production in the area where implanted. Today, the investigators can say that there are experimental and clinical evidence supporting the effectiveness of the method. The investigators have designed a phase II clinical trial to check the feasibility of this approach.

Official Title
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Phase II Clinical Trial of Tissue Engineering Based on the Use of Mononuclear Cells From Autologous Bone Marrow Seeded on Porous Tricalcium Phosphate Biomaterial in Patients With Pseudoarthrosis

Conditions
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Pseudoarthrosis

Intervention / Treatment
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* Procedure: ABM seeded onto a porous TCP and DBM
* Procedure: autologous bone graft


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pseudarthrosis of tibia established any cause with at least 9 months. The pseudarthrosis is not to show signs of healing in the last 3 months. The pseudarthrosis subsidiary should not be solely osteosynthesis treatment. Age between 18 and 75 years. Serology Human Immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) negative. Negative pregnancy test in women of childbearing age. Patient sufficient guarantees of adherence to protocol. Signature written informed consent before a witness Exclusion Criteria: Systemic infection. Septic pseudoarthrosis. Insufficient skin coverage at the site of nonunion. Vascular insufficiency in the affected limb. Pathological fracture. Concomitant psychiatric or neurological disease. Concurrent or prior malignancy treated with chemotherapy over a period of less than 1 year. Concomitant severe disease not well controlled. Inclusion in other clinical trials. Inability to understand the informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABM seeded onto a porous TCP and DBM<br>ABM seeded onto a porous TCP and DBM | Procedure: ABM seeded onto a porous TCP and DBM<br>* cells collection under sedation . 114 mL are obtained and processed through a ficoll gradient. Autologous bone marrow (ABM) cells seeded onto a porous tricalcium phosphate ceramic (TCP) and demineralized bone matrix (DBM)<br>|
| Active Comparator: autologous bone graft<br>autologous bone graft | Procedure: autologous bone graft<br>* autologous bone graft<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time needed to repair the focus of necrosis measured by pain radiography |  | Baseline and every 14 days up to 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain scale |  | Baseline and every 14 days up to 180 days | 
| Technical success | Understood as having been able to perform the implant of calcium phosphate matrix loaded with more than 100 million mononuclear cells | 6 months | 
| Morbidity | Infection of extraction points Pathological fracture of the extraction area Muscle hernia Stress fracture Infection of focus repaired Rupture of the focus fixture repaired Appearance of secondary malignancies | 6 months | 
| Absence of adverse events |  | 6 months | 
| physical exploratory |  | Baseline and every 14 days up to 180 days | 
| Analgesia Scale |  | Baseline and every 14 days up to 180 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fractures, Bone, Stem Cells