Autologous Mesenchymal Stem Cells vs. Chondrocytes for the Repair of Chondral Knee Defects

Study Overview
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Brief Summary
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The objective of our study is to compare the safety and effectiveness of the use of autologous cultured adipose tissue-derived stem cells versus cultured autologous chondrocytes for the treatment of chondral knee lesions.

Detailed Description
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Chondral knee lesions are frequent and produce important functional limitations and arthrosis development. Arthrosis is one of the most important causes of disability and its treatment with prosthetic surgery is associated with a high cost, and is not free of other complications. Several studies of cell therapy with autologous chondrocytes have shown efficacy in the treatment of this type of lesions, and currently is a common technique for the treatment of focal lesions of articular cartilage. Autologous chondrocyte transplant is associated with morbidity of the cartilage sample removal, which needs intra-articular surgery, and the limited tissue sample for culture. Adipose tissue-derived mesenchymal stem cells (ASC) have demonstrated chondrocytic differentiation and have been used in animal models for articular cartilage repair. Adipose tissue yields more ASC than chondrocytes are obtained from cartilage, and liposuction is simple and with less adverse events than arthroscopy. It is worth mentioned that culture conditions are less stringent for ASC than for chondrocytes, in terms of number of passages to obtain the amount of cells needed for implantation. We propose a randomized clinical trial, in which we compare the surgical implantation of either autologous chondrocytes or autologous ASC to treat chondral knee lesions.

Official Title
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A Comparative Clinical Trial for the Repair of Chondral Knee Defects: Transplantation of Autologous Cultured Chondrocytes vs. Autologous Mesenchymal Stem Cells Derived From Adipose Tissue

Conditions
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Articular Cartilage Lesion of the Femoral Condyle

Intervention / Treatment
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* Other: Implantation of autologous cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic focal articular cartilage lesion on the medial femoral condyle Lesion on femoral condyle between 1 and 5 cm² ICRS Grade III/IV Stable knee Signed patient informed consent Exclusion Criteria: Clinically relevant member malalignment (> 5 degrees) Non stable knee Inflammatory joint disease Knee surgery in the last year (transplant, suture or resection of the meniscus, mosaicplasty, microfracture) Participation in concurrent trials or in the previous 3 months Subjects with hepatitis, HIV or syphilis Malignancy in the previous 5 years Alcohol and/or drug abuse Poor general health as judged by Investigator Clinically relevant second cartilage lesion on the patella Patellofemoral cartilage lesion Known allergy to gentamicin or penicillins (or presence of multiple severe allergies) Having received hyaluronic acid intra-articular injections in the affected knee within the last 6 months of baseline Taking specific OA drugs such as chondroitin sulfate, diacerein, n-glucosamine, piascledine, capsaicin within 2 weeks of the baseline visit Corticosteroid treatment by systemic or intra-articular route within the last month of baseline or intramuscular or oral corticosteroids within the last 2 weeks of baseline Chronic use of anticoagulants Uncontrolled diabetes Any concomitant painful or disabling disease of the spine,hips or lower limbs that would interfere with evaluation of the afflicted knee Any clinically significant or symptomatic vascular or neurologic disorder of the lower extremities Liver enzymes (SGOT, SGPT, Alkaline Phosphatase) of more then two times the upper limit of normal or any other result that is clinically important according to the Investigator CRP > 10 mg/l

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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 |
| --- | --- |
| Experimental: Autologous ASC implantation<br>Treatment with autologous ASC | Other: Implantation of autologous cells<br>* Implantation of autologous ASC or chondrocytes, 1 million per cm² lesion, covered by autologous periosteal membrane<br>* Other names: ACI;|
| Active Comparator: Autologous Chondrocytes implantation<br>Treatment with autologous chondrocytes | Other: Implantation of autologous cells<br>* Implantation of autologous ASC or chondrocytes, 1 million per cm² lesion, covered by autologous periosteal membrane<br>* Other names: ACI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hyaline cartilage production for chondral knee lesions repair |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Clinical evolution | Changes in Clinical tests and SF-12 Health Survey over 18 months | 18 months | 
| Efficacy: Functional evolution | Changes in Western Ontario-McMaster Osteoarthritis Score(WOMAC) over 18 months | 18 months | 
| Efficacy: Functional evolution | Changes in Knee Society Score(KSS) over 18 months | 18 months | 
| Efficacy: Histological evaluation | Hyaline cartilage production by histological methods at 18 months | 18 months | 
| Efficacy: Radiological evaluation | MRI at 18 months | 18 months | 
| Safety: Adverse events | Sistemic and local AEs especially attributable to implanted cells | 18 months | 
| Safety: Acute inflammatory events | Increase of pain of at least 30 mm on a 100 mm visual analog scale (VAS) along with self-reported swelling within 3 days post-cell application | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cartilage, Articular, Femoral, Knee, Chondrocytes, Adipose tissue-derived mesenchymal stem cells