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

• ClinicalTrials.gov Identifier: NCT01586312
• Recruitment Status: Completed
• First Posted: April 26, 2012
• Results First Posted: November 6, 2014
• Last Update Posted: October 16, 2015
• Sponsor: Red de Terapia Celular
• Collaborators: University of Valladolid; Sanidad de Castilla y León; Centro Medico Teknon
• Information provided by (Responsible Party): Red de Terapia Celular

Study Description

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 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.

Condition or disease	Intervention/treatment	Phase
Osteoarthritis, Knee; Arthritis of Knee; Knee Osteoarthritis	Other: Allogenic mesenchymal stromal cells injection; Drug: Hyaluronic Acid	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Treatment of Knee Osteoarthritis With Allogenic Mesenchymal Stem Cells (MSV*) *MSV: Mesenchymal Stromal Cells From Valladolid
• Study Start Date: April 2012
• Actual Primary Completion Date: December 2013
• Actual Study Completion Date: June 2014

Arms and Interventions

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: MSV; Mesenchymal Stem Cells; MSC
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 Name: Hyaluronic acid, durolane, CE mark:516407

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to one year ]
   Adverse events reported. Clinical review and questionaires for pain, disability and quality of life at 0, 3, 6 and 12 months

Secondary Outcome Measures :

1. Pain and Disability Evolution (WOMAC, Visual Analogue Scale, Lequesne Index and SF-12 Scores) [ Time Frame: up to one year ]

   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.

2. Evolution of Cartilage Degeneration by T2 Relaxation Measurements in MRI (Cartigram) [ Time Frame: up to one year ]

   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Spain

Centro Medico Teknon

Barcelona, Spain, 08022

Hospital Clinico Universitario

Valladolid, Spain, 47003

Sponsors and Collaborators

Red de Terapia Celular

University of Valladolid

Sanidad de Castilla y León

Centro Medico Teknon

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

More Information

Additional Information:

Cell Therapy Network 

MSV providing 

osteoarthritis, knee 

mesenchymal stem cells 

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Red de Terapia Celular
• ClinicalTrials.gov Identifier: NCT01586312
• 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 )
• First Posted: April 26, 2012
• Results First Posted: November 6, 2014
• Last Update Posted: October 16, 2015
• Last Verified: September 2015

Keywords provided by Red de Terapia Celular:

Knee degenerative disease; osteoarthritis; gonarthrosis; stem cell; cellular therapy; regenerative therapy; Mesenchymal stem cells; Bone marrow; musculoskeletal Diseases; Mesenchymal Stromal Cells (allogenic)

Additional relevant MeSH terms:

Osteoarthritis; Osteoarthritis, Knee; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Hyaluronic Acid; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs; Viscosupplements; Protective Agents