Treatment of Degenerative Disc Disease With Allogenic Mesenchymal Stem Cells (MSV)

Study Overview
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Brief Summary
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In this study we want to evaluate the clinical use of allogenic mesenchymal stem cells (MSC), obtained from bone marrow of healthy donors, for treatment of Degenerative Disc Disease (DDD). The trial is based in previous results with autologous MSC (Orozco et al., Transplantation 92: 822-828; 2011). Here we propose a phase I-II trial, prospective, randomized, blinded, and controlled for the treatment DDD using MSV, a Good Manufacturing Practice (GMP)-compliant expanded bone marrow MSC (MSV, PEI Num. 10-134). The assay consists of two arms with 12 patients each one. Patients in the experimental arm will be given a single intra-discal transplantation of MSV (25 millions in 2 ml). Control patients will be infiltrated in the paravertebral muscles close to the lesion with 2 ml of 1% mepivacain. We shall follow the evolution of pain, disability and quality of life as well as disc fluid content by Magnetic Resonance Imaging (T2-calibrated).

Official Title
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Treatment of Lumbar Degenerative Disc Disease With Allogenic Mesenchymal Stem Cells (MSV*) *MSV: Bone Marrow Mesenchymal Stromal Cells Expanded Using the Valladolid IBGM Procedure

Conditions
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Degenerative Disc Disease, Intervertebral Disc Disease, Low Back Pain

Intervention / Treatment
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* Biological: Allogenic Mesenchymal Stromal Cells
* Drug: Mepivacaine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Degenerative disease of one or two lumbar discs with predominant back pain after conservative treatment (physical and medical) for over 6 months. Fibrous ring capable of holding the cell implantation, demonstrated by RMI image (stages 2, 3 and 4 of Adams). Decrease of disc height of more than 20% (radiographic measurement in side image). Absence of spinal infection. Haematological and biochemical analysis wit no significant alterations that contraindicates intervention. The patient is able to understand the nature of the study. Informed written consent of the patient. Exclusion Criteria: Age over 75 or under 18 or legally dependent Allergy to gentamicin, or to bovine, cattle or horse serum. Congenital or acquired diseases leading to spine deformations that may upset cell application. Spinal segmental instability, spinal canal stenosis, isthmus pathology and other conditions that may compromise the study Modic III changes on MRI images (31). Overweight with body mass index (mass in Kg/size in m2) greater than 35 (obesity grade II). Pregnancy or breast-feeding Neoplasia Immunosuppression Participation in another clinical trial or treatment with another investigational product within 30 days prior to inclusion in the study. Other conditions that may, according to medical criteria, discourage participation in the study.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Allogenic Mesenchymal Stromal Cells<br>Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intradiscal injection of 25 millions MSC in 2 ml of saline | Biological: Allogenic Mesenchymal Stromal Cells<br> <br> * Other names: MSV (MSV=MSC prepared following Valladolid IBGM procedure);|
| Active Comparator: Mepivacaine<br>Infiltration of paravertebral musculature close to the affected disc(s) with 2 ml of 1% Mepivacaine | Drug: Mepivacaine<br> <br> * Other names: Mepivacaine is also known as Polocaine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability | Number of participants with adverse events will be used as a measure of safety and tolerability. Adverse events reported: clinical review and questionaires for pain, disability and quality of life at 0, 3, 6 and 12 months | up to one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain and disability evolution | Clinical review and questionaires (Visual Analogue Scales (VAS) and Oswestry questionnaires) at 0, 3, 6 and 12 months. | up to 1 year | 
| Evolution of affected disc(s) by quantitative Magnetic Resonance Imaging (RMI) | RMI density measurements in T2 weighted images performed at 0, 6 and 12 months used as an indication of disc fluid content | up to one year | 
| Llife quality evolution (Short Form (SF)-12 questionnaire) | SF-12 scores at 0, 3, 3 and 12 months | up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Degenerative Disc Disease,, Intervertebral Disc Disease, Low Back Pain, Nucleus pulposus, Stem cell, Cellular therapy, Regenerative therapy, Mesenchymal stem cells, Bone marrow, Musculoskeletal Diseases, Mesenchymal Stromal Cells (allogenic)