"One-step" Bone Marrow Mononuclear Cell Transplantation in Talar Osteochondral Lesions
Condition: Osteochondritis
MeSH terms: Osteochondritis
Study type: Interventional

Summary: 
      BACKGROUND Osteochondral lesions are defects of the cartilaginous surface and underlying
      subchondral bone of the talar dome.

      The use of concentrated bone marrow derived cells has been gaining successful results with
      arthroscopic implantation, since it is possible to transplant not only mesenchymal stem cells
      but also accessory cells that support angiogenesis and vasculogenesis by producing several
      growth factors.

      OBJECTIVES Objective of this project is to identify the critical points of the regenerative
      treatment of osteochondral lesions of the ankle, in order to develop a standard and
      predictable procedure able to overcome the drawbacks of the previous techniques.

      METHODS Our program is to evaluate and follow 140 new patients with focal osteochondral
      lesion of the talus. The surgical procedure will be executed as following: the day before the
      surgery the platelet gel will be produced. The day of the surgery bone marrow will be
      aspirate from the posterior iliac crest and concentrated directly in the operating room by
      centrifugation, in order to obtain 6 mL of concentrate containing nucleated cells.

      Then a standard ankle arthroscopy will be performed. The scaffold will be loaded with 2 ml of
      bone marrow concentrate and cut into an appropriate shape.

      After the scaffold implantation platelet gel will be sprayed on the top of implant, in order
      to provide extra growth factors and to improve the stability of the implant.

      All patients will be examined clinically preoperatively, at 3, 6, 12, 24 and 36 months and at
      maximum follow-up. Different score scales will be used to objectivate the clinical results
      (AOFAS, SF-36, VAS). X-rays and MRI scan will be also taken preoperatively, and MRI will be
      executed at 12, 24 and 36 months of follow-up. In particular, a new qualitative MRI called T2
      mapping will be performed at 24 months.

      EXPECTED RESULTS We expect to highlight the effectiveness of the arthroscopic bone marrow
      derived cells (BMDCs) transplantation in a long term follow up study, with particular
      attention to identify the patient population that can gain the maximum benefit from this
      treatment, avoiding expensive and unnecessary procedures that too often are performed.
    

Detailed description: 
      Study design The study will be an observational prospective study. 46 patients previously
      operated in our center by Autologous Chondrocyte Implantation (ACI) will be used as control.

      Patients 140 patients with osteochondral lesions of the talar dome will be recruited for this
      study. All the procedures will be performed according with specific European and Italian
      guidelines.

      The patients will be operated as inpatients in the II Clinic of Orthopaedics and
      Traumatology. This is an highly specialized ward for the treatment of foot and ankle
      diseases. During the first day of hospitalization the patients will undergo a complete blood
      test and standard X-rays examination, along with specialized anesthesiologist, hematological
      and orthopaedic examinations.

      Key inclusion and exclusion criteria Patients must satisfy the following inclusion criteria:
      osteochondral lesions of the talar dome ICRS grade III or IV lesion, size of the lesion >1.5
      cm2, age <50 years.

      Key exclusion criteria will take into account the presence of arthritis, kissing lesions,
      ankle malalignment and ankle instability, articular infections, hematological or rheumatic
      disorders.

      Treatment The surgical procedure will be executed as following: the day before the surgery
      120 ml of venous blood will be collected for the platelet gel production performed with an
      automatic method by Unit 5. The day of the surgery, 60 ml of bone marrow will be aspirate
      from the posterior iliac crest of the patient and concentrated directly in the operating room
      by a specific device (kit IOR-G1, Novagenit, Mezzolombardo, TN, Italy), in order to obtain 6
      mL of concentrate bone marrow (CBM) containing nucleated cells (stem cells, monocytes,
      lymphocytes, and other bone marrow resident cells). After the bone marrow harvesting phase, a
      standard ankle arthroscopy will be performed, with the patient in the supine position. The
      lesion will be detected and cleaned.

      An equine collagen type 1 scaffold (IOR-G1, Novagenit, Mezzolombardo, TN, Italy) will be
      loaded with 2 ml of bone marrow concentrate and cut into an appropriate shape to fit the
      lesion.

      After the scaffold implantation 2 ml of platelet gel will be loaded on the top of implant, in
      order to provide growth factors and to improve the stability of the implant.

      Patient will be hospitalized for 2 days after surgery. Examinations, MRI and X-rays will be
      performed in ambulatory in outpatients regimen at the outpatients facility of Rizzoli
      Orthopaedic Institute.

      The evaluation of the different growth factors present in bone marrow releasate was also
      performed in order to highlight the differences among patient samples.

      Statistical analysis (Potency) with calculation Continuous data will be described as means
      and standard deviations. Qualitative data will be expressed as frequencies and percentages.
      The Kolmogorov-Smirnov test will be used to evaluate the normality of data distribution. The
      Levene test will be used to analyze the homoscedasticity. Differences between preoperative
      and follow up data will be evaluated with the paired t test for homoscedastic and normally
      distributed data; otherwise, the nonparametric Wilcoxon-Mann-Whitney test will be used.
      Differences between groups will be evaluated with the unpaired t test for homoscedastic and
      normally distributed data; otherwise, the nonparametric Wilcoxon-Mann-Whitney test will be
      used. Pearson's correlation will be performed to investigate the relationships between
      continuous variables if they will be both normally distributed; otherwise, the Spearman rank
      correlation test will be used. Statistical analysis will be performed using SPSS® software
      (Version 15.0; SPSS Inc, Chicago, IL).

      Ethical aspect All the patients, in order to be enrolled in this study, must sign a specific
      informed consent, approved from an independent ethical committee.

      Risk for patients Risk for the patients will be the risk related to the surgical procedure.
      They include anesthetics (local or general), procedure-related risk such as infection, deep
      venous thrombosis, damages of anatomical structures. It is important to underline that all
      these risks are not specifically related with this procedure, but with all the procedures
      involving an ankle arthroscopy with cartilage treatment. The risks for the patients will be
      minimized with specific training activities for all the personnel taking part to the project
      (i.e nurses, operating room personnel, attending surgeons, hematologists, residents) . Data
      will be evaluated by a statistician , and all the monitoring activities will be performed by
      dedicated personnel.

      Good clinical practice For each patient entered into the study a Case Record Form (CRF) in
      compliance with Good Clinical Practice will prepared. This document does not coincide with
      the subject's clinical personal folder. It must be given all the data elements relevant to
      the study. The coordinator of the trial will provide a CFR copy in electronic format to the
      PU involved. The compilation and maintenance of CRF as well as data transmission to the
      scientific director of the WP are under the responsibility of the leader of the PU involved.

      Patient data will be collected in dedicated databases (on special software) that will enable
      safe storage and processing, to ensure the privacy of patients.
    

Intervention name(s): bone marrow cells transplantation on collagen scaffold
Intervention type(s): Procedure
Intervention description(s): 120 ml of venous blood will be collected for the platelet gel production. The day of the surgery, 60 ml of bone marrow will be aspirate from the posterior iliac crest and concentrated. a standard ankle arthroscopy will be performed, with the patient in the supine position. The lesion will be detected and cleaned.
An equine collagen type 1 scaffold (IOR-G1, Novagenit, Mezzolombardo, TN, Italy) will be loaded with 2 ml of bone marrow concentrate and cut into an appropriate shape to fit the lesion.
After the scaffold implantation 2 ml of platelet gel will be loaded on the top of implant, in order to provide growth factors and to improve the stability of the implant.
Other intervention name(s): kit IOR-G1, a collagen scaffold; Autologous platelet gel will be implanted on the scaffold
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: osteochondral lesion; talus; ankle; cartilage repair