Safety Study of Mesenchymal Stem Cells and Spinal Fusion

Study Overview
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Brief Summary
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The present prospective, randomized study, compares the spinal fusion obtained after instrumentation and the use of a biologic product (patient's mesenchymal cells obtained from his/her own bone marrow which will be fixed in human bone tissue form a donor), with the current procedure that consists in instrumented spinal fusion and the use of each patient's bone obtained from his/her iliac crest. The working hypothesis proposes that the tissue engineering is a valid and useful technique to achieve bone regeneration, avoiding the need for obtaining patient's iliac crest and its associated morbidity.

Detailed Description
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Prospective, open-label, randomized, parallel, single-dose phase I-II clinical trial in which 62 patients affected with L4-L5 degenerative spondylolisthesis grade I-II according to Meyerding and/or with L4-L5 degenerative discopathy needing spinal fusion 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 spinal fusion. Secondary objectives are to assess the efficacy of the implantation by imaging (computerized helicoidal tomography and X-ray) and clinical questionnaires (pain by visual analogue scale, quality of life by SF-36 and Oswestry Disability Index). Patients will be randomized to one of the two treatment arms (instrumented spinal fusion and the tissue engineering product composed by ex-vivo expanded autologous mesenchymal stem cells fixed in allogenic bone tissue in spinal fusion or the standard treatment of instrumented spinal fusion and patient's bone iliac crest). Thereafter, patients will be followed for 12 months. Imaging assessment will be done by an independent blinded radiologist.

Official Title
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Ex Vivo Expanded Autologous Bone Marrow Mesenchymal Stem Cells Fixed in Allogenic Human Bone Tissue for Spinal Fusion in Spine Degenerative Disease

Conditions
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Lumbar Spondylolisthesis Involving L4-L5, and/or, Degenerative Discopathy Involving L4-L5

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: L4-L5 degenerative spondylolisthesis grade I-II Meyerding isolated or associated to more than one level, and/or L4-L5 degenerative discopathy isolated or associated to more than one level. 18 to 85 years of age (male and female) Informed Consent Form signed The patient is able to understand the nature of the study Exclusion Criteria: Previous spine surgery L4 isthmic spondylolisthesis Smoker (more than 10 cigarettes a day) Systemic or local infection Patients treated with steroids (oral or systemic) within 3 months of entering the study, or treated with biphosphonates for more than 10 years 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 (except diabetes mellitus. Treatment with therapies is allowed) Significant abnormal laboratory tests that contraindicates the surgery. Participation in another clinical trial or treated with an investigational medicinal product the previous 3 months 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 that could exceed the clinical trial length The patient is legally dependent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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 for spinal fusion | Biological: XCEL-MT-OSTEO-ALPHA<br>* Isolation and ex-vivo expansion of mesenchymal stem cells (MSC) obtained from each patient's bone marrow under GMP conditions at Xcelia, División de Terapias Avanzadas delBanc de Sang i Teixits. After expansion, MSCs are fixed in allogenic bone tissue and implanted in instrumented spinal fusion.<br>|
| Sham Comparator: Standard treatment<br>Instrumented spinal fusion together with patient's bone iliac crest. | Procedure: Standard treatment<br>* Instrumented spinal fusion together with patient's bone iliac crest<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 (tissue engineering product composed by ex-vivo expanded autologous mesenchymal stem cells fixed in allogenic bone tissue in spinal fusion) | 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 (composed by ex-vivo expanded autologous mesenchymal stem cells fixed in allogenic bone tissue in spinal fusion) | 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 |
| --- | --- | --- |
| Efficacy spinal fusion by imaging procedures (X-Ray). | Spinal fusion will be assessed by spinal X-Ray | 3, 6 and 12 months | 
| Efficacy spinal fusion by imaging procedures (computerized helicoidal tomography) | Spinal fusion will be assessed by the presence of solid bonny bridges using computerized helicoidal tomography. | 6 and 12 months | 
| Clinical outcomes (VAS) | Pain measurement by visual analogue scale (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 (Oswestry Disability Index) | To assess the extent by which a person's functional level is restricted by disability by the Oswestry Disability 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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Spondylolisthesis, Degenerative discopathy, Mesenchymal Stem Cells, Bone marrow, Tissue engineering, Spinal fusion