Treatment of Knee Osteoarthritis by Intra-articular Injection of Bone Marrow Mesenchymal Stem Cells

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) in patients with knee osteoarthritis. Patients and methods Clinical trial phase I- II, randomized , multicenter , with three treatment arms and 10 patients for each group. The investigators compare the intraarticular injection of hialuronic acid against the administration of two different doses of mesenchymal stem cells with hialuronic acid according to the following scheme: Group A: intra-articular injection of hyaluronic acid (Hyalone®). Single dose. Group B: Low Dosage of MSCs . Intra-articular injection of 10 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 Hiaurónico Acid ( Hyalone®). Group C : High dose of MSCs. 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 Hiaurónico Acid (Hyalone®). 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.

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) in patients with knee osteoarthritis. Patients and methods Clinical trial phase I- II, randomized , multicenter , with three treatment arms and 10 patients for each group. The investigators compare the intraarticular injection of hialuronic acid against the administration of two different doses of mesenchymal stem cells with hialuronic acid according to the following scheme: Group A: intra-articular injection of hyaluronic acid (Hyalone®). Single dose. Group B: Low Dosage of MSCs . Intra-articular injection of 10 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 Hiaurónico Acid ( Hyalone®). Group C : High dose of MSCs. 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 Hiaurónico Acid (Hyalone®). The autologous mesenchymal stem cells are obtained from the iliac crest and cultured ex vivo under local anesthesia and sedation. 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: Inclusion Criteria: Males and females between 50 and 80 year old. 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. Allergy to hyaluronic acid or poultry proteins.

Official Title
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Treatment of Osteoarthritis by Intra-articular Injection of Bone Marrow Mesenchymal Stem Cells

Conditions
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Osteoarthritis

Intervention / Treatment
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* Drug: Hyaluronic acid
* Biological: 10 million Bone marrow mesenchimal stem cells
* Biological: 100 million Bone marrow mesenchimal stem cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females between 50 and 80 year old. 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. Allergy to hyaluronic acid or poultry proteins.

Ages Eligible for Study
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Minimum Age: 50 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hialuronic acid<br>Single intraarticular injection of Hyaluronic acid (Hyal One) | Drug: Hyaluronic acid<br>* Single intraarticular injection of Hyaluronic acid (Hyal One)<br>* Other names: HyalOne;|
| Active Comparator: Hyaluronic acid and MSC 10<br>Single intraarticular injection of Hyaluronic acid (Hyal One) 10 million Bone marrow mesenchimal stem cells | Drug: Hyaluronic acid<br>* Single intraarticular injection of Hyaluronic acid (Hyal One)<br>* Other names: HyalOne;Biological: 10 million Bone marrow mesenchimal stem cells<br>* 10 million of Bone marrow mesenchimal stem cells<br>|
| Active Comparator: Hyaluronic acid AND MSC 100<br>Single intraarticular injection of Hyaluronic acid (Hyal One) 100 million Bone marrow mesenchimal stem cells | Drug: Hyaluronic acid<br>* Single intraarticular injection of Hyaluronic acid (Hyal One)<br>* Other names: HyalOne;Biological: 100 million Bone marrow mesenchimal stem cells<br>* 100 million of Bone marrow mesenchimal stem cells<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) | prior to the initial dose on 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). | Prior to the intervention on day 1 | 
| Baseline Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC). | Prior to the intervention on day 1 Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC). | Prior to the intervention on day 1 | 
| Baseline SF-36 value | Prior to the intervention on day 1 SF-36 value | Prior to the intervention on day 1 | 
| Baseline euroquol 5D value | Pretreatment euroquol 5D value | Prior to the intervention on day 1 | 
| Baseline Lequesne index | Prior to the intervention on day 1 Lequesne index | Prior to the intervention on day 1 | 
| Baseline femorotibial distance | Prior to the intervention femoritibial distance on rosenberg x-ray view | Prior to the intervention | 
| 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 | During the follow up | Follow up | 
| Visual analogue scale (VAS) at on 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 | 
| Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 1 month | Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 1 month | 1 month | 
| Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 3 month | Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 1 month | 3 months | 
| Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 6 month | Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 6 month | 6 months | 
| Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 12 months | Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 12 months | 12 months | 
| SF-36 value at 1 month | SF-36 value | 1 month | 
| SF 36 value at 3 months | SF 36 value at 3 months | 3 months | 
| SF 36 value at 6 months | SF 36 value at 6 months | 6 months | 
| SF 36 value at 12 months | SF 36 value at 12 months | 12 months | 
| Euroquol 5D value at 1 month | Euroquol 5D value at 1 month | 1 MOnth | 
| Euroquol 5D value at 3 months | Euroquol 5D value at 3 months | 3 months | 
| Euroquol 5D value at 6 months | Euroquol 5D value at 6 months | 6 months | 
| Euroquol 5D value at 12 months | Euroquol 5D value at 12 months | 12 months | 
| Lequesne index at 1 month | Lequesne index at 1 month | 1 month | 
| Lequesne index at 3 months | Lequesne index at 3 months | 3 months | 
| Lequesne index at 6 months | Lequesne index at 6 months | 6 months | 
| Lequesne index at 12 months | Lequesne index at 12 months | 12 months | 
| Femorotibial distance at 6 months | Femorotibial distance at 6 months | 6 months | 
| Femorotibial distance at 12 months | Femorotibial distance at 12 months | 12 months | 
| Baseline MRI WORMS protocol | Prior to the intervention MRI WORMS protocol | Prior to the intervention | 
| MRI WORMS protocol score at 6 months | MRI WORMS protocol score at 6 months | 6 months | 
| MRI WORMS protocol score at 12 months | MRI WORMS protocol score at 12 months | 12 months | 

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