Clinical trial NCT01860417: Treatment of Degenerative Disc Disease With Allogenic Mesenchymal Stem Cells (MSV)
Official title: Treatment of Lumbar Degenerative Disc Disease With Allogenic Mesenchymal Stem Cells (MSV*) *MSV: Bone Marrow Mesenchymal Stromal Cells Expanded Using the Valladolid IBGM Procedure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Degenerative Disc Disease
Intervertebral Disc Disease
Low Back Pain
Keywords: 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)
Lead sponsor: Red de Terapia Celular
Sponsor class: INDUSTRY
Collaborators: name: Citospin
name: University of Valladolid
First posted: 2013-05-22
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Pain and Disability Evaluation
timeFrame: Change since the baseline (before intervention) up to the end of the follow-up period, 12 months after the intervention
Secondary outcomes:
measure: Evaluation of Affected Disc(s) by Quantitative MRI Ratio 12/6months
timeFrame: At 12 months from 6 months after the intervention
measure: Evaluation of Affected Disc(s) by Quantitative Magnetic Resonance Imaging (RMI): Density at 6 Months
timeFrame: At 6 months after the intervention
measure: Evaluation of Affected Disc(s) by Quantitative Magnetic Resonance Imaging (RMI): Density at 12 Months
timeFrame: At 12 months after the intervention
measure: Visual Analogue Scale at 3 Months
timeFrame: At 3 months after the intervention
measure: Visual Analogue Scale at 6 Months
timeFrame: At 6 months after the intervention
measure: Visual Analogue Scale at 12 Months
timeFrame: At 12 months after the intervention
measure: Oswestry Disability Index at 3 Months
timeFrame: At 3 months after the intervention
measure: Oswestry Disability Index at 6 Months
timeFrame: At 6 months after the intervention
measure: Oswestry Disability Index at 12 Months
timeFrame: At 12 months after the intervention
measure: SF-12 Physical Component at 3 Months
timeFrame: 3 months after the intervention
measure: SF-12 Physical Component at 6 Months
timeFrame: 6 months after the intervention
measure: SF-12 Physical Component at 12 Months
timeFrame: 12 months after the intervention
measure: SF-12 Mental Component at 3 Months
timeFrame: 3 months after the intervention
measure: SF-12 Mental Component at 6 Months
timeFrame: 6 months after the intervention
measure: SF-12 Mental Component at 12 Months
timeFrame: 12 months after the intervention
measure: Pfirrmann Stage at 6 Months
timeFrame: At 6 months after the intervention
measure: Pfirrmann Stage at 12 Months
timeFrame: At 12 months after the intervention
Other outcomes:
Locations:
city: Valladolid
country: Spain
facility: Hospital Clinico Universitario
city: Valladolid
country: Spain
facility: Instituto de Biologia y Genetica Molecular
Study officials:
affiliation: Scientific Park Foundation of University of Valladolid
name: Javier Garcia-Sancho, MD, PhD
role: STUDY_CHAIR
affiliation: Hospital Clinico Universitario, Valladolid
name: David C Noriega, MD, PhD
role: STUDY_DIRECTOR
affiliation: Citospin
name: Ana Sanchez, MD, PhD
role: STUDY_DIRECTOR
affiliation: Hospital Clinico Universitario, Valladolid
name: FRancisco Ardura, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.