Treatment of Knee Osteoarthritis With Allogenic Mesenchymal Stem Cells

Study Overview
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Brief Summary
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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.

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

Conditions
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Osteoarthritis, Knee, Arthritis of Knee, Knee Osteoarthritis

Intervention / Treatment
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* Other: Allogenic mesenchymal stromal cells injection
* Drug: Hyaluronic Acid


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Allogenic mesenchymal stromal cells injection<br>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<br>* 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<br>* Other names: MSC;|
| Active Comparator: Hyaluronic acid (Durolane)<br>Intraarticular injection of hyaluronic acid (60 mg) | Drug: Hyaluronic Acid<br>* Intra-articular injection of 60 mg of hyaluronic acid (Durolane) in a single injection (3 ml)<br>* Other names: Hyaluronic acid, durolane, CE mark:516407;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bone marrow, Knee degenerative disease, osteoarthritis, gonarthrosis, stem cell, cellular therapy, regenerative therapy, Mesenchymal stem cells, musculoskeletal Diseases, Mesenchymal Stromal Cells (allogenic)