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

Phase 1

Completed

Conditions: Low Back Pain
Intervertebral Disc Disease
Degenerative Disc Disease

Interventions: Biological: Allogenic Mesenchymal Stromal Cells
Drug: Mepivacaine

Registration Number: NCT01860417

Lead Sponsor: Red de Terapia Celular

Brief Summary: 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, Investigational medicinal product 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 24

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 Magnetic resonance imaging (MRI) 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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Allogenic Mesenchymal Stromal Cells	Allogenic Mesenchymal Stromal Cells	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
Mepivacaine	Mepivacaine	Infiltration of paravertebral musculature close to the affected disc(s) with 2 ml of 1% Mepivacaine

Primary Outcome Measures

Name	Time	Method
Pain and Disability Evaluation	Change since the baseline (before intervention) up to the end of the follow-up period, 12 months after the intervention	Change in the composite variable, which includes pain and disability 1 year after intervention, was plotted as a function of the initial pain score or disability index. Results for the relief of lumbar pain and Oswestry disability index were all included for both, control and cell-treated patients. The scores obtained from this analysis (slope of the plot) range from 0 to 1, with higher scores meaning a better outcome.

Secondary Outcome Measures

Name	Time	Method
Oswestry Disability Index at 3 Months	At 3 months after the intervention	Subject's Disability score in the Oswestry Disability Index (ODI) before intervention. Outcomes are expressed using a 0%-100% scale. Zero is equated with no disability and 100 is the maximum disability possible
Oswestry Disability Index at 12 Months	At 12 months after the intervention	Subject's Disability score in the Oswestry Disability Index (ODI) before intervention. Outcomes are expressed using a 0%-100% scale. Zero is equated with no disability and 100 is the maximum disability possible
SF-12 Physical Component at 6 Months	6 months after the intervention	Results from the physical component of the short form-12 (SF-12) life quality questionnaire. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning
Evaluation of Affected Disc(s) by Quantitative MRI Ratio 12/6months	At 12 months from 6 months after the intervention	Ratio discs density: Discs density at 12 months divided by discs density at 6 months after transplantation. To homogenize the results of different patients, the water content values of the affected discs were normalized to the values obtained from the healthy discs in the same individual; for these purposes, the density of the affected segments was divided by the average value of the healthy discs. Finally, the value after the treatment was divided by the baseline value.
Visual Analogue Scale at 12 Months	At 12 months after the intervention	Pain evaluation using a visual analogue scale (VAS) at baseline. Outcomes are expressed using a 0%-100% scale. A higher score indicates greater pain intensity
SF-12 Physical Component at 12 Months	12 months after the intervention	Results from the physical component of the short form-12 (SF-12) life quality questionnaire. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning
Evaluation of Affected Disc(s) by Quantitative Magnetic Resonance Imaging (RMI): Density at 12 Months	At 12 months after the intervention	Measurement of the amount of fluid in the disc. To homogenize the results of different patients, the water content values of the affected discs were normalized to the values obtained from the healthy discs in the same individual; for these purposes, the density of the affected segments was divided by the average value of the healthy discs. Finally, the value after the treatment was divided by the baseline value.
SF-12 Physical Component at 3 Months	3 months after the intervention	Results from the physical component of the short form-12 (SF-12) life quality questionnaire. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning
Visual Analogue Scale at 3 Months	At 3 months after the intervention	Pain evaluation using a visual analogue scale (VAS) at baseline. Outcomes are expressed using a 0%-100% scale. A higher score indicates greater pain intensity
Visual Analogue Scale at 6 Months	At 6 months after the intervention	Pain evaluation using a visual analogue scale (VAS) at baseline. Outcomes are expressed using a 0%-100% scale. A higher score indicates greater pain intensity
Oswestry Disability Index at 6 Months	At 6 months after the intervention	Subject's Disability score in the Oswestry Disability Index (ODI) before intervention. Outcomes are expressed using a 0%-100% scale. Zero is equated with no disability and 100 is the maximum disability possible
SF-12 Mental Component at 3 Months	3 months after the intervention	Results from the mental component of the short form-12 (SF-12) life quality questionnaire. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning
SF-12 Mental Component at 6 Months	6 months after the intervention	Results from the mental component of the short form-12 (SF-12) life quality questionnaire. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning
Pfirrmann Stage at 12 Months	At 12 months after the intervention	Grades: Gr I: Disc homogeneous. Bight hyperintense white signal intensity. Normal height Gr II: Disc inhomogeneous. Hyperintense white signal. Nucleus/annulus clearly differentiated. Height is normal Gr III: Disc inhomogeneous. Intermittent gray signal intensity. Unclear distinction nucleus/annulus. Height normal/slightly decreased Gr IV: Disc inhomogeneous. Hypointense dark gray signal intensity. No distinction nucleus/annulus. Height slightly/moderately decreased. Gr V: Disc inhomogeneous. Hypointense black signal intensity. No distinction nucleus/annulus. Disc space is collapsed
Evaluation of Affected Disc(s) by Quantitative Magnetic Resonance Imaging (RMI): Density at 6 Months	At 6 months after the intervention	Measurement of the amount of fluid in the disc. To homogenize the results of different patients, the water content values of the affected discs were normalized to the values obtained from the healthy discs in the same individual; for these purposes, the density of the affected segments was divided by the average value of the healthy discs. Finally, the value after the treatment was divided by the baseline value.
SF-12 Mental Component at 12 Months	12 months after the intervention	Results from the mental component of the short form-12 (SF-12) life quality questionnaire. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning
Pfirrmann Stage at 6 Months	At 6 months after the intervention	Grades: Gr I: Disc homogeneous. Bight hyperintense white signal intensity. Normal height Gr II: Disc inhomogeneous. Hyperintense white signal. Nucleus/annulus clearly differentiated. Height is normal Gr III: Disc inhomogeneous. Intermittent gray signal intensity. Unclear distinction nucleus/annulus. Height normal/slightly decreased Gr IV: Disc inhomogeneous. Hypointense dark gray signal intensity. No distinction nucleus/annulus. Height slightly/moderately decreased. Gr V: Disc inhomogeneous. Hypointense black signal intensity. No distinction nucleus/annulus. Disc space is collapsed