Efficacy of Bone-marrow-derived and Placenta-derived Multipotent Mesenchymal Stem / Stromal Cells for Osteoarthritis

Study Overview
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Brief Summary
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To define the clinical effects of intra-articular transplantation of bone-marrow-derived (BM-MMSCs) and placenta-derived multipotent mesenchymal stem / stromal cells (P-MMSCs) for knee osteoarthritis.

Detailed Description
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Multipotent mesenchymal stem / stromal cells (MMSCs) of different origin are the novel therapeutic agents that can slow down cartilage degeneration, improve reparation and ultimately prevent joint prosthetics. MSCs are capable to direct differentiation into chondrocytes, produce cytokines and growth factors with immunomodulatory and anti-inflammatory effects, stimulate angiogenesis, as well as induce chemotaxis of endogenous progenitors. Bone marrow-derived and placenta-derived MMSCs can be considered the most promising source for cell therapy of joints disorders according to availability, safety and expected therapeutic efficacy.

Official Title
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Efficacy of Bone-marrow-derived and Placenta-derived Multipotent Mesenchymal Stem / Stromal Cells for Osteoarthritis

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Biological: Placenta-derived MMSCs
* Biological: Bone marrow-derived MMSCs
* Drug: Hyalgan 20 mg in 2 ML Prefilled Syringe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of knee osteoarthritis. Age: 18 to 75 years old. Kellgren-Lawrence Grade 2 or 3 according to X-ray imaging. Knee pain. Written informed consent Exclusion Criteria: Age <18 or >75 years of age by time of infusion. Participation in an on-going investigational therapeutic or device trial 30 days of consent. Rheumatoid arthritis. Psoriatic arthritis. Juvenile idiopathic arthritis. Gout. Infectious arthritis. Osteomyelitis. Osteonecrosis. Inflammatory arthritis. Chondropathy. Joint contracture. Arthroplasty. Arthroscopy within 6 months prior to study entry. Intra-articular injection within 3 months prior to study entry. Hormone intake. Antiaggregants and anticoagulants intake. Immunosuppressants intake. Allergy to hyaluronic acid. History of organ or cell transplantation. Hematologic abnormality evidenced by hematocrit < 25%, white blood cell < 2,500/ul or platelet count < 100,000/ul. Active infection. Positive for HIV antigen. History of hepatitis B, hepatitis C. History of malignancy in the last 5 years prior to study entry. Active tumors. History of myocardial infarction. History of stroke. Renal failure with chronic hemodialysis. Liver Cirrhosis (ICGR 15 >30%). Chromosomal abnormality. Peripheral nervous system disorders. Cognitive or language barriers that prohibit obtaining informed consent or any study elements. History of drug abuse or alcohol abuse, or documented medical, occupational, or legal problems arising from the use of alcohol or drugs within the past 24 months. Pregnant/nursing women or women of child-bearing potential. Other condition that limits lifespan to < 1 year.

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: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Experimental: HA + stem cells therapy Experimental Group 1: three intra-articular injection of allogeneic P-MMSCs with up to 2•107cells (target dose up to 6•107 cells) with 20 mg Hyaluronic Acid at 4-weeks intervals - 15 patients Experimental Group 2: three intra-articular injection of autologous BM-MMSCs up to 2•107cells (target dose up to 6•107 cells) with 20 mg Hyaluronic Acid at 4-weeks intervals - 15 patients Control Group: three intra-articular injection of 20 mg Hyaluronic Acid, no cell therapy - 15 patients
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hyaluronic Acid (HA) + P-MMSCs<br>Experimental Group 1: Three intra-articular injection of allogeneic P-MMSCs up to 2•107cells (target dose up to 6•107 cells) with 20 mg Hyaluronic Acid at 4-weeks intervals - 15 patients | Biological: Placenta-derived MMSCs<br>* Cryopreserved placenta-derived multipotent mesenchymal stem / stromal cells<br>* Other names: P-MMSCs;Drug: Hyalgan 20 mg in 2 ML Prefilled Syringe<br>* Hyaluronic Acid 20 mg<br>* Other names: HA;|
| Experimental: Hyaluronic Acid (HA) + BM-MMSCs<br>Experimental Group 2: Three intra-articular injection of autologous BM-MMSCs up to 2•107cells (target dose up to 6•107 cells) with 20 mg Hyaluronic Acid at 4-weeks intervals - 15 patients | Biological: Bone marrow-derived MMSCs<br>* Cryopreserved bone marrow-derived multipotent mesenchymal stem / stromal cells<br>* Other names: BM-MMSCs;Drug: Hyalgan 20 mg in 2 ML Prefilled Syringe<br>* Hyaluronic Acid 20 mg<br>* Other names: HA;|
| Active Comparator: Hyaluronic Acid (HA)<br>Three intra-articular injection of 20 mg Hyaluronic Acid - 15 patients | Drug: Hyalgan 20 mg in 2 ML Prefilled Syringe<br>* Hyaluronic Acid 20 mg<br>* Other names: HA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events and changes in physical examinations, vital signs and the results of clinical lab tests. | Treatment-related adverse events | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical function improvement measured by Western Ontario and McMaster Universities Arthritis Index (WOMAC). | Change in joint function from baseline WOMAC assessment. The WOMAC used a scoring scale of 0-4 (lower scores indicate lower levels of symptoms or physical disability). The higher the score, the higher the amount of pain, stiffness, and a high level of functional limitations. | 12 months. | 
| Radiographic evidence. Whole-Organ Magnetic Resonance Imaging Score (WORMS) | Change in cartilage thickness of the knee using MRI | 12 months | 
| Quality of Life (QOL) assessment | Change in scores on the QOL | 12 months | 
| The Visual Analog Scale (VAS) assessment | VAS - measure of pain intensity. The scale is most commonly anchored by no pain  (score of 0) and worst imaginable pain (score of 10). | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BM-MMSCs;, P-MMSCs;, Hyaluronic Acid