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

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

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).

Study Overview

• Status: Completed
• Conditions: Low Back Pain; Degenerative Disc Disease; Intervertebral Disc Disease
• Intervention / Treatment: Biological: Allogenic Mesenchymal Stromal Cells; Drug: Mepivacaine

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Valladolid, Spain, 47003
    • Hospital Clínico Universitario
  • Valladolid, Spain, 47003
    • Instituto de Biologia y Genetica Molecular

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Biological: Allogenic Mesenchymal Stromal Cells; Other Names: Mesenchymal stem cells (MSC); MSC injection; MSV (MSV=MSC prepared following Valladolid IBGM procedure)
Active Comparator: Mepivacaine; Infiltration of paravertebral musculature close to the affected disc(s) with 2 ml of 1% Mepivacaine	Drug: Mepivacaine; Other Names: Sham-treated comparator; Mepivacaine is also known as Carbocaine; Mepivacaine is also known as Polocaine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain and Disability Evaluation	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.	Change since the baseline (before intervention) up to the end of the follow-up period, 12 months after the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of Affected Disc(s) by Quantitative MRI Ratio 12/6months	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.	At 12 months from 6 months after the intervention
Evaluation of Affected Disc(s) by Quantitative Magnetic Resonance Imaging (RMI): Density at 6 Months	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.	At 6 months after the intervention
Evaluation of Affected Disc(s) by Quantitative Magnetic Resonance Imaging (RMI): Density at 12 Months	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.	At 12 months after the intervention
Visual Analogue Scale at 3 Months	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	At 3 months after the intervention
Visual Analogue Scale at 6 Months	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	At 6 months after the intervention
Visual Analogue Scale at 12 Months	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	At 12 months after the intervention
Oswestry Disability Index at 3 Months	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	At 3 months after the intervention
Oswestry Disability Index at 6 Months	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	At 6 months after the intervention
Oswestry Disability Index at 12 Months	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	At 12 months after the intervention
SF-12 Physical Component at 3 Months	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	3 months after the intervention
SF-12 Physical Component at 6 Months	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	6 months after the intervention
SF-12 Physical Component at 12 Months	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	12 months after the intervention
SF-12 Mental Component at 3 Months	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	3 months after the intervention
SF-12 Mental Component at 6 Months	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	6 months after the intervention
SF-12 Mental Component at 12 Months	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	12 months after the intervention
Pfirrmann Stage at 6 Months	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	At 6 months after the intervention
Pfirrmann Stage at 12 Months	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	At 12 months after the intervention

Collaborators and Investigators

• Sponsor: Red de Terapia Celular
• Collaborators: University of Valladolid; Citospin
• Investigators: Study Chair: Javier Garcia-Sancho, MD, PhD, Scientific Park Foundation of University of Valladolid; Study Director: David C Noriega, MD, PhD, Hospital Clinico Universitario, Valladolid; Study Director: Ana Sanchez, MD, PhD, Citospin; Principal Investigator: FRancisco Ardura, MD, PhD, Hospital Clinico Universitario, Valladolid

Publications and helpful links

General Publications

• Orozco L, Soler R, Morera C, Alberca M, Sanchez A, Garcia-Sancho J. Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study. Transplantation. 2011 Oct 15;92(7):822-8. doi: 10.1097/TP.0b013e3182298a15.
• Noriega DC, Ardura F, Hernandez-Ramajo R, Martin-Ferrero MA, Sanchez-Lite I, Toribio B, Alberca M, Garcia V, Moraleda JM, Sanchez A, Garcia-Sancho J. Intervertebral Disc Repair by Allogeneic Mesenchymal Bone Marrow Cells: A Randomized Controlled Trial. Transplantation. 2017 Aug;101(8):1945-1951. doi: 10.1097/TP.0000000000001484.

Helpful Links

• Treatment of Degenerative Disc Disease with Autologous Mesenchymal Stem Cells
• Citospin S.L. (MSV Cell Production)
• Intervertebral disk
• mesenchymal stem cells
• Instituto de Biologia y Genética Molecular IBGM), Cell Production Research

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2013
• Primary Completion (Actual): December 15, 2015
• Study Completion (Actual): December 15, 2015

Study Registration Dates

• First Submitted: May 18, 2013
• First Submitted That Met QC Criteria: May 18, 2013
• First Posted (Estimated): May 22, 2013

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Low Back Pain; Musculoskeletal Diseases; Mesenchymal stem cells; Bone marrow; Stem cell; Cellular therapy; Degenerative Disc Disease,; Intervertebral Disc Disease; Nucleus pulposus; Regenerative therapy; Mesenchymal Stromal Cells (allogenic)
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Bone Diseases; Back Pain; Low Back Pain; Intervertebral Disc Degeneration; Spinal Diseases; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Mepivacaine
• Other Study ID Numbers: TerCel005; 2012-004444-30 (EudraCT Number); Disc_allo_MSV (Other Identifier: Red TerCel)