Treatment of Knee Osteoarthritis With Autologous Mesenchymal Stem Cells
Condition: Osteoarthritis, Knee; Knee Degenerative Disease; Knee Osteoarthritis
MeSH terms: Osteoarthritis; Osteoarthritis, Knee
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      In this prospective study we aim to evaluate the feasibility and safety of the implantation
      of 40 millions MSV in knees with osteoarthritis of grade II-IV (Kellgren and Lawrence). The
      working hypothesis proposes that MSV antiinflammatory effect will help healing of articular
      cartilage degeneration to a grade enough to be objectivized by questionnaires and imaging
      procedures. The study of quantitative changes in structure and composition of cartilage
      determined by MRI T2-mapping (Cartigram ) will be performed at 6, 12 and 24 months. Pain and
      disability will be assessed by visual analogue scale (VAS), WOMAC, Lequesne Index and
      evaluation of the quality of life by Short Form 36 questionnaire (SF-36) completed at 3, 6,12
      and 24 months.
    

Detailed description: 
      Knee osteoarthritis is the most common form of arthritis. Treatments involve high costs in
      terms of social and economic, are palliative and do not contemplate healing by regenerative
      therapy. It has been shown recently, that mesenchymal stem cells (MSC) can be expanded "in
      vitro" and may regenerate several damaged or injured tissues. In addition its has
      demonstrated that MSC are able to modulate immune responses and to control inflammation
      through its action on T lymphocytes. Preliminary studies in animal models, including one
      carried out in an equine by our research group, confirms feasibility, safety and efficacy
      evidence proposed treatment protocol. Our research group has also experience in preparing
      clinical-grade MSC from bone marrow for other clinical trials and has all the necessary
      facilities and permissions to comply with GMPs imposed by recent EU legislation. Finally, our
      clinical team has a wide experience in regenerative therapies in several previous clinical
      trials for bone and cartilage.

      We present here an alternative proposal, aiming to anti-inflammation and regeneration by
      injection of single dose of mesenchymal stem cells expanded from autologous bone marrow by
      the GMP-complying IBGM-Valladolid procedure (MSV). Treatment involves two non-invasive
      surgical procedures with low morbidity: obtaining bone marrow under local anesthesia and
      sedation, and 4 weeks later, articular injection of the cell product (20 millions MSVs). The
      injection of cells does not even require anesthesia and obtaining bone marrow requires an
      outpatient admission two hours following safety criteria.

      Patients will be evaluated clinically, including pain score (VSA), pain and disability
      indexes (WOMAC and Lequesne) and life quality (SF-36), and by radiologic and MRI procedures
      no contrast and allowing quantification of morphological and structural changes of the
      cartilage region studied (MRI T2-mapping).

      The design of the study is an open-label prospective, multicenter study. It will recruit 12
      patients with osteoarthritis of II-IV Kellgren and Lawrence grades, Patients will be
      evaluated clinically by previous studies imaging (X-rays and MRI). If they are eligible for
      the study we shall provide them information about the clinical trial with the "Patient
      Information Sheet, quoting them for the Inclusion Visit. In the "Inclusion Visit" if the
      patient decides to participate in the test should sign the Informed Consent Document and a
      schedule for MRI and X-rays will be scheduled. The results of this exploration will be
      considered the standard to which compare any given change in the controls at 6 and 12 months.
      On this visit, routine preoperative examinations are performed (EKG, chest X-ray AP, basic
      analytic coagulation tests and identification of HIV, Lues and hepatitis B and C and the
      valuation by the Internal Medicine Service).

      During the visit V0 we shall verify that all inclusion criteria persist and not exclusion
      criteria have appeared, and we shall program V1 (to obtain bone marrow) and provide a
      preliminary date for MSV injection 4 week later (V2). After application, the patients will
      have follow-up schedule at 8 days (V3), 3 (V4), 6 (V5), 12 (V6) and eventually 24 months (V7)
      as detailed below.

      V0: Eligibility. Clinical History. Analysis, Imaging test. Programming of the following
      visits V1 (day 0): Bone marrow aspiration under local anesthesia and sedation V2 (day 23).
      MSV Implantation. V3 (+8 days from Implantation): Security evaluation. V4 (+3 months from
      Implantation): Security evaluation. VAS, WOMAC, Lequesne Index, SF-36 questionnaires.

      V5 (+6 months from Implantation): Security evaluation. VAS, WOMAC, Lequesne Index, SF-36
      questionnaires, RX, RNM.

      V6 (+12 months from Implantation): Security evaluation. VAS, WOMAC, Lequesne Index, SF-36
      questionnaires, RX, RNM.

      V7 (+24 months from Implantation): Security evaluation. VAS, WOMAC, Lequesne Index, SF-36
      questionnaires, RX, RNM.
    

Intervention name(s): Autologous bone marrow mesenchymal stem cells (MSV)
Intervention type(s): Other
Intervention description(s): Bone marrow collection from patient, mesenchymal cells isolation and expansion under GMP conditions following the IBGM-Valladolid protocol (MSV). Autologous MSV implantation by articular injection.
Other intervention name(s): MSV, mesenchymal stem cells by IBGM-Valladolid protocol.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Knee degenerative disease; osteoarthritis; gonarthrosis; stem cell; cellular therapy; regenerative therapy; Mesenchymal stem cells; Bone marrow; musculoskeletal Diseases