Treatment of Osteoarthritis by Intra-articular Injection of Bone Marrow Mesenchymal Stem Cells With Platelet Rich Plasma

Study Overview
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Brief Summary
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Purpose: To determine the safety, feasibility and effectiveness (clinical and radiological) of intra-articular administration of autologous mesenchymal stem cells (MSCs) with platelet richa plasma (PRGF) in patients with knee osteoarthritis. Patients and methods Clinical trial phase I- II, randomized , multicenter , with two treatment arms and 19 patients for each group. The investigators compare the intraarticular injection of against the administration of two different doses of mesenchymal stem cells with hialuronic acid according to the following scheme: Group A: 3 intra-articular injections of platelet rich plasma (PRGF®) separated by 7 days. Group B: 3 intra-articular injections of platelet richa plasma (PRGF®) separated by 7 days and one with Mesenchimal stems cells. Intra-articular injection of 100 million autologous mesenchymal progenitor stem cells cultured ex - vivo (cell suspension sterile small volume (5-10 ml ) in a vehicle suitable for intraarticular injection ) followed by an intraarticular injection of platelet richa plasma (PRGF®). The treatment is completed with 2 more injection of platelet richa plasma (PRGF®) separeted by one week. In addition the investigators assess the response to intra-articular infusion of CMM analyzing the following parameters: Clinical assessment of pain and function (Baseline, 1, 3, 6 and 12 months since treatment): VAS , WOMAC , KOOS , EuroQol, SF-16, Lequesne , WOMAC , KOOS. Radiographic (baseline and 12 months from treatment): Femorotibial space. Radiographic using MRI (baseline and 12 months from treatment): by assessing the number location of the lesions , cartilage thickness , signal intensity , subchondral bone alteration , volume and WORMS and dGEMRIC protocols.

Detailed Description
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Purpose: To determine the safety, feasibility and effectiveness (clinical and radiological) of intra-articular administration of autologous mesenchymal stem cells (MSCs) with platelet richa plasma (PRGF®) in patients with knee osteoarthritis. Patients and methods Clinical trial phase I- II, randomized , multicenter , with two treatment arms and 19 patients for each group. The investigators compare the intraarticular injection of against the administration of two different doses of mesenchymal stem cells with hialuronic acid according to the following scheme: Group A: 3 intra-articular injections of platelet richa plasma (PRGF®) separated by 7 days. Group B: 3 intra-articular injections of platelet richa plasma (PRGF®) separated by 7 days and one with Mesenchimal stem cell. Intra-articular injection of 100 million autologous mesenchymal progenitor stem cells cultured ex - vivo (cell suspension sterile small volume (5-10 ml ) in a vehicle suitable for intraarticular injection ) followed by an intraarticular injection of platelet richa plasma (PRGF®). The treatment is completed with 2 more injection of platelet richa plasma (PRGF®) separeted by one week. The autologous mesenchymal stem cells are obtained from the iliac crest under local anesthesia and sedation. They are cultured ex vivo The primary endpoint is safety and feasibility. The investigators registered the occurrence of complications and / or adverse effects during the study. In addition the investigators assess the response to intra-articular infusion of CMM analyzing the following parameters: Clinical assessment of pain and function (Baseline, 1, 3, 6 and 12 months since treatment): VAS , WOMAC , KOOS , EuroQol, SF-16, Lequesne , WOMAC , KOOS. Radiographic (baseline, 6 and 12 months since treatment): Femorotibial space. Radiographic using MRI (baseline, 6 and 12 months since treatment): by assessing the number location of the lesions , cartilage thickness , signal intensity , subchondral bone alteration , volume and WORMS and dGEMRIC protocols. All patients met the following inclusion and exclusion criteria:

Official Title
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Phase I/II. Treatment of Osteoarthritis by Intra-articular Injection of Bone Marrow Mesenchymal Stem Cells With Platelet Rich Plasma(PRGF)

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Biological: 100 million Bone marrow mesenchimal stem cells
* Biological: Platelet Rich plasma (PRGF)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females between 40 and 80 year old Bad results with previous hyaluronic acid injection Diagnosis of knee OA according to the criteria of osteoarthritis of the ACR (American College of Rheumatology) Joint pain equal or greater than 2.5 points on the visual analogue scale (VAS) Radiological Classification: Kellgren-Lawrence scale greater or equal to 2 Body mass index between 20 and 35 kg/m2 Ability to follow during the study period Exclusion Criteria: Bilateral Osteoarthritis of the Knee requiring treatment in both knees Previous diagnosis of polyarticular disease Severe mechanical deformation Arthroscopy during the previous 6 months Intraarticular infiltration of hyaluronic acid in the last 6 months Systemic autoimmune rheumatic disease Poorly controlled diabetes mellitus Blood dyscrasias Immunosuppressive or anticoagulant treatments Treatment with corticosteroids in the 3 months prior to inclusion in the study NSAID therapy within 15 days prior to inclusion in the study Patients with a history of allergy to penicillin or streptomycin

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Platelet Rich Plasma (PRGF)<br>Platelet Rich plasma (PRGF) 3 intraarticular onjections sepataded by 7 days. | Biological: Platelet Rich plasma (PRGF)<br>* 3 injections of PRGF<br>|
| Active Comparator: BMMSC with Platelet Rich Plasma (PRGF)<br>Single intraarticular injection of 100 million Bone marrow mesenchimal stem cells and three intraarticular injections of plateler Rich Plasma (PRGF) separatede by 7 days. | Biological: 100 million Bone marrow mesenchimal stem cells<br>* 100 million Bone marrow mesenchimal stem cells with PRGF<br>Biological: Platelet Rich plasma (PRGF)<br>* 3 injections of PRGF<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Visual analogue scale (VAS) Baseline Visual analogue scale (VAS) | Baseline Visual analogue scale (VAS) prior to the initial dose on day 1 | Day 1 | 
| Baseline value of knee injury and osteoarthritis outcome score (Koos). | Prior to the intervention on day 1 value of knee injury and osteoarthritis outcome score (Koos). | Day 1 | 
| Baseline Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC). | Universities Osteoarthritis Index score (WOMAC). | Day 1 | 
| Baseline SF-36 value | Baseline SF-36 value | Day 1 | 
| Baseline euroquol 5D value | Pretreatment euroquol 5D value | Day 1 | 
| Baseline Lequesne index | Prior to the intervention on day 1 Lequesne index | Day 1 | 
| Baseline femorotibial distance | Prior to the intervention femoritibial distance on rosenberg x-ray view | Day 1 | 
| Number of Participants with Serious and Non-Serious Adverse Events Number of Participants with Serious and Non-Serious Adverse Events Number of Participants with Serious and Non-Serious Adverse Events | Participants with Serious and Non-Serious Adverse Events Number of Participants with Serious and Non-Serious Adverse Events During the follow up | Follow up (up to 12 months) | 
| Visual analogue scale (VAS) at 1 month | Visual analogue scale (VAS) at on month | 1 month | 
| Visual analogue scale (VAS) at 3 months | Visual analogue scale (VAS) at 3 months | 3 months | 
| Visual analogue scale (VAS) at 6 months | Visual analogue scale (VAS) at 6 months | 6 months | 
| Visual analogue scale (VAS) at 12 months | Visual analogue scale (VAS) at 12 months | 12 months | 
| Value of knee injury and osteoarthritis outcome score (Koos) at 1 month | Value of knee injury and osteoarthritis outcome score (Koos) at 1 month | 1 month | 
| Value of knee injury and osteoarthritis outcome score (Koos) at 3 month | Value of knee injury and osteoarthritis outcome score (Koos) at 3 month | 3 Months | 
| Value of knee injury and osteoarthritis outcome score (Koos) at 6 month | Value of knee injury and osteoarthritis outcome score (Koos) at 6 month | 6 months | 
| Value of knee injury and osteoarthritis outcome score (Koos) at 12 months | Value of knee injury and osteoarthritis outcome score (Koos) at 12 months | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Knee Osteoarthritis, Mesenchimal stem cell, Osteoarthritis