Mesenchymal Stem Cells in Osteonecrosis of the Femoral Head

Study Overview
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Brief Summary
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The present study evaluates the effect of XCEL-MT-OSTEO-ALPHA in osteonecrosis of the femoral head in comparison to the standard treatment of isolated core decompression. XCEL-MT-OSTEO-ALPHA is a tissue engineering product composed by ex-vivo expanded autologous mesenchymal stem cells fixed in allogenic bone tissue. The working hypothesis proposes that the tissue engineering is a valid and useful technique to achieve bone regeneration, avoiding the progression to collapse of the femoral head.

Detailed Description
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Prospective, open-label with blinded assessor, randomized, parallel, single-dose phase I-II clinical trial in which 24 patients affected with osteonecrosis of the femoral head ARCO grade I or II will enter the trial with the primary objective of assessing the feasibility and safety of ex-vivo expanded autologous mesenchymal stem cells fixed in allogenic bone tissue in osteonecrosis of the femoral head. Secondary objectives are to assess the efficacy of the implantation by imaging (magnetic resonance imaging) and clinical questionnaires (pain by visual analogue scale, quality of life by SF-36 and WOMAC Index). Patients will be randomized to one of the two treatment arms (core decompression and the tissue engineering product composed by ex-vivo expanded autologous mesenchymal stem cells fixed in allogenic bone tissue or the standard treatment of isolated core decompression). Thereafter, patients will be followed for 12 months.

Official Title
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A Pilot Clinical Trial of ex Vivo Expanded Autologous Bone Marrow Mesenchymal Stem Cells Fixed in Allogenic Human Bone Tissue (XCEL-MT-OSTEO- ALPHA) in Osteonecrosis of the Femoral Head

Conditions
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Avascular Necrosis of Femur Head

Intervention / Treatment
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* Biological: XCEL-MT-OSTEO-ALPHA
* Procedure: Standard treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 50 years of age (male and female) Osteonecrosis of the hip ARCO grade I or II Abscence of systemic or local infection Laboratory tests with no relevant abnormal findings that contraindicate the surgery. Informed Consent Form signed The patient is able to understand the nature of the study Exclusion Criteria: Osteonecrosis of the hip secondary to femoral neck fracture Patients with no closed cartilage Surgical implants in the femoral head Septic arthritis Patients with severe renal insufficiency Patients expecting or with liver transplantation Positive serology for HIV-1 or HIV-2, Hepatitis B (HBsAg), Hepatitis C (Anti-HCV-Ab) or Syphilis. Pregnant woman or intended to become pregnant, or breath feeding Neoplasia within the previous 5 years, or without remission Immunosuppressive states The patient is legally dependent Participation in another clinical trial or treated with an investigational medicinal product the previous 30 days Cardiac pacemaker, allergy to contrast or any other condition that contraindicates the MRI with contrast agents Other pathologic conditions or circumstances that difficult participation in the study according to medical criteria The patient does not accept to be followed-up for a period thar could exceed the clinical trial length

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: XCEL-MT-OSTEO-ALPHA<br>ex-vivo expanded autologous mesenchymal stem cells fixed in allogenic bone tissue (under Xcelia-GMP conditions)for osteonecrosis of the femoral head | Biological: XCEL-MT-OSTEO-ALPHA<br>* Core decompression plus XCEL-MT-OSTEO-ALPHA<br>|
| Sham Comparator: Standard Treatment<br>Isolated core decompression | Procedure: Standard treatment<br>* Isolated core decompression<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of XCEL-MT-OSTEO-ALPHA in osteonecrosis of the femoral head | Safety will be assessed by collecting adverse events throughout the experimental phase, which includes a follow-up of 12 months | 12 months | 
| Feasibility of XCEL-MT-OSTEO-ALPHA in osteonecrosis of the femoral head | Feasibility will be measured by assessing the percentage of patients to which bone marrow puncture is made are thereafter treated and by checking the cascade of procedures to confirm the global process is viable. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone regeneration by measuring the necrotic angle using the modified Kerboul method | The necrotic angle will be measured using imaging procedures (magnetic resonance imaging MRI). | 6 and 12 months | 
| Dynamic changes of signal intensity | Dynamic changes of signal intensity after Gd enhancement in the necrotic areas of the femoral head | 6 and 12 months | 
| Clinical outcomes (pain) by Visual Analogue Scale (VAS) | Pain measurement by VAS | 7 days and at 3, 6 and 12 months | 
| Clinical outcomes (SF-36) | This clinical outcome will measure the quality of life by the self-reported quality of life questionnaire SF-36 | 3, 6 and 12 months | 
| Clinical outcome (WOMAC) | To assess the extent by which a person's functional level is restricted by the WOMAC index | 3, 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Avascular Necrosis of Femur Head, Osteonecrosis of the hip, Osteonecrosis of the femoral head, Mesenchymal Stem Cells, Bone marrow, Tissue engineering, Bone Diseases, Musculoskeletal Diseases