Pseudoarthrosis
Conditions
Keywords
Fractures, Bone, Stem Cells
Brief summary
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
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.
Interventions
PROCEDUREABM seeded onto a porous TCP and DBM
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)
PROCEDUREautologous bone graft
autologous bone graft
Sponsors
Carlos III Health Institute
Hospital Universitario Virgen de la Arrixaca
Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time needed to repair the focus of necrosis measured by pain radiography | Baseline and every 14 days up to 180 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Technical success | 6 months | Understood as having been able to perform the implant of calcium phosphate matrix loaded with more than 100 million mononuclear cells |
| Morbidity | 6 months | 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 |
| Pain scale | Baseline and every 14 days up to 180 days | — |
| physical exploratory | Baseline and every 14 days up to 180 days | — |
| Analgesia Scale | Baseline and every 14 days up to 180 days | — |
| Absence of adverse events | 6 months | — |
Countries
Spain
Outcome results
None listed