Treatment of Knee Osteoarthritis by Intra-articular Injection of Bone Marrow Mesenchymal Stem Cells
Condition: Osteoarthritis
MeSH terms: Osteoarthritis
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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:

        1. Group A: intra-articular injection of hyaluronic acid (Hyalone®). Single dose.

        2. 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®).

        3. 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: 
      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:

        1. Group A: intra-articular injection of hyaluronic acid (Hyalone®). Single dose.

        2. 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®).

        3. 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.
    

Intervention name(s): Hyaluronic acid; 10 million Bone marrow mesenchimal stem cells; 100 million Bone marrow mesenchimal stem cells
Intervention type(s): Drug; Biological; Biological
Intervention description(s): Single intraarticular injection of Hyaluronic acid (Hyal One); 10 million of Bone marrow mesenchimal stem cells; 100 million of Bone marrow mesenchimal stem cells
Other intervention name(s): HyalOne
Intervention MeSH terms: Hyaluronic Acid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Osteoarthritis; Mesenchimal stem cell; Knee