Treatment of Knee Osteoarthritis With Allogenic Mesenchymal Stem Cells (MSV_allo)

Treatment of Knee Osteoarthritis With Allogenic Mesenchymal Stem Cells (MSV*) *MSV: Mesenchymal Stromal Cells From Valladolid

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 knee osteoarthritis. The trial is based in our own previous results with autologous MSC (ongoing NCT01183728 trial). We propose here a multicenter, phase I-II clinical trial, prospective, randomized, blinded, and controlled for the treatment of osteoarthritis (degrees II and III and IV). The assay consists of two arms with 15 patients each one. Patients in the experimental arm will be given an intra-articular transplantation of allogenic MSC, expanded "Ex Vivo" with our GMP-compliant procedure (MSV, PEI No. 10-134, authorized by the Competent Authority; same as in NCT01183728). In the control arm a standard treatment with intra-articular injection of hyaluronic acid shall be given. We shall follow the evolution of pain, disability, quality of life and quantitative changes in structure and composition of cartilage determined by T2-weighted MRI relaxation (Cartigram) for one year.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis; Osteoarthritis, Knee; Arthritis of Knee
• Intervention / Treatment: Other: Allogenic mesenchymal stromal cells injection; Drug: Hyaluronic Acid

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08022
    • Centro Médico Teknon
  • Valladolid, Spain, 47003
    • Hospital Clínico Universitario

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Knee osteoarthritis grade II, III and IV of Kellgren and Lawrence assessed by two observers.
• Chronic knee pain with mechanical characteristics.
• No local or systemic septic process.
• Haematological and biochemical analysis without significant alterations that contraindicate treatment.
• Informed written consent of the patient.
• The patient is able to understand the nature of the study

Exclusion Criteria:

• Age over 75 or under 18 years or legally dependent
• Present Infection (to be included in the study no signs of infection must be evidenced)
• Congenital or acquired malformation resulting in significant deformity of the knee (varus<10º; valgus<20º) and leading to problems in application or evaluation of results.
• Overweight expressed as body mass index (BMI) greater than 30.5 (obesity grade II). BMI estimated as mass (kg) / corporal surface (m2).
• Women who are pregnant or intend to become pregnant or breast-feeding
• Neoplasia
• Immunosuppressive states
• Intra-articular infiltartion of any treatments in the last 3 months previous to study inclusion
• Participation in another clinical trial or treatment with a different investigational product within 30 days prior to inclusion in the study.
• Other pathologic conditions or circumstances that difficult participation in the study according to medical criteria

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Allogenic mesenchymal stromal cells injection; Mesenchymal stem cells (MSC) prepared from bone marrow from healthy donor expanded ex vivo for 3-4 weeks. Intraarticular injection of 40 millions MSC.	Other: Allogenic mesenchymal stromal cells injection; Mesenchymal stem cells prepared from bone marrow of healthy donors and expanded for 3-4 weeks according to our procedure described in PEI Num. 10-134, authorized by the Spanish Medicine Agency; Other Names: Mesenchymal Stem Cells; MSC; MSV
Active Comparator: Hyaluronic acid (Durolane); Intraarticular injection of hyaluronic acid (60 mg)	Drug: Hyaluronic Acid; Intra-articular injection of 60 mg of hyaluronic acid (Durolane) in a single injection (3 ml); Other Names: Hyaluronic acid, durolane, CE mark:516407

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events 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 (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores)	Clinical review, questionaires for pain, disability and quality of life at 0, 3, 6 and 12 months. WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index): Questionnaire to quantify the pain, stiffness and physical function in patients with osteoarthritis of the knee or hip. SF-12 (Short Form 12, an abbreviated form of SF36) is a questionnaire for the detection of changes in quality of life. The visual analogue scale (VAS) is a psychometric response scale which can be used for subjective measurements of knee pain. LEQUESNE algofunctional index: is a composite measure of pain and disability, with specific self-report questionnaires for knee (osteoarthritis). All the scale ranges ranges (minimum and maximum scores) are between 0 and 100%. Values are given in differences from baseline (usually negative values). More negative values show more improvement on both scales.	up to one year
Evolution of Cartilage Degeneration by T2 Relaxation Measurements in MRI (Cartigram)	Magnetic Resonance imaging measurements of T2 relaxation (Cartigram) performed at 0, 6 and 12 months to quantify articular cartilage degeneration. The values (in milliseconds) are T1/2 for decay of the T2 MRI signals. Normal values are below 50 ms; values above 50 ms correspond to inflamed cartilage. Mean (SD) are expressed as the number of values (of a total of 88 measurements) that are between 50 and 90 ms. A value =<4.4 is considered normal (can be attained by chance). Values above 4.4 are considered pathological. The worst possible is 88.	up to one year

Collaborators and Investigators

• Sponsor: Red de Terapia Celular
• Collaborators: Centro Medico Teknon; University of Valladolid; Sanidad de Castilla y León
• Investigators: Study Chair: Javier García-Sancho, MD, PhD, University of Valladolid, Scientific Park; Study Director: Aurelio Vega, MD,PhD, Hospital Clinico Universitario, Valladolid; Study Director: Luis Orozco, MD, PhD, Centro Médico Teknon, Barcelona; Study Director: Ana Sanchez, MD, PhD, Director, Cell Production Unit, Parque Científico UVa; Study Director: Jose M Moraleda, MD. PhD, Virgen de la Arrixaca University Hospital, Murcia, Spain

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.
• Orozco L, Munar A, Soler R, Alberca M, Soler F, Huguet M, Sentis J, Sanchez A, Garcia-Sancho J. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study. Transplantation. 2013 Jun 27;95(12):1535-41. doi: 10.1097/TP.0b013e318291a2da.
• Orozco L, Munar A, Soler R, Alberca M, Soler F, Huguet M, Sentis J, Sanchez A, Garcia-Sancho J. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: two-year follow-up results. Transplantation. 2014 Jun 15;97(11):e66-8. doi: 10.1097/TP.0000000000000167. No abstract available.
• Vega A, Martin-Ferrero MA, Del Canto F, Alberca M, Garcia V, Munar A, Orozco L, Soler R, Fuertes JJ, Huguet M, Sanchez A, Garcia-Sancho J. Treatment of Knee Osteoarthritis With Allogeneic Bone Marrow Mesenchymal Stem Cells: A Randomized Controlled Trial. Transplantation. 2015 Aug;99(8):1681-90. doi: 10.1097/TP.0000000000000678.

Helpful Links

• mesenchymal stem cells
• Cell Therapy Network
• MSV providing
• osteoarthritis, knee

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: April 23, 2012
• First Submitted That Met QC Criteria: April 24, 2012
• First Posted (Estimate): April 26, 2012

Study Record Updates

• Last Update Posted (Estimate): October 16, 2015
• Last Update Submitted That Met QC Criteria: September 26, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: osteoarthritis; stem cell; Mesenchymal stem cells; Bone marrow; cellular therapy; gonarthrosis; Mesenchymal Stromal Cells (allogenic); Knee degenerative disease; regenerative therapy; musculoskeletal Diseases
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: TerCel004; 2011-005321-51 (EudraCT Number); EC11-309 (Other Grant/Funding Number: Spanish Ministry of Health, Independent Clinical Investigatio); MSV_allo (Registry Identifier: Protocol code)