Clinical trial NCT01399749: Autologous Mesenchymal Stem Cells vs. Chondrocytes for the Repair of Chondral Knee Defects
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Articular Cartilage Lesion of the Femoral Condyle
Keywords: Cartilage
Articular
Femoral
Knee
Chondrocytes
Adipose tissue-derived mesenchymal stem cells
Lead sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz
Sponsor class: OTHER
First posted: 2011-07-22
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Hyaline cartilage production for chondral knee lesions repair
timeFrame: 18 months
Secondary outcomes:
measure: Efficacy: Clinical evolution
timeFrame: 18 months
measure: Efficacy: Functional evolution
timeFrame: 18 months
measure: Efficacy: Functional evolution
timeFrame: 18 months
measure: Efficacy: Histological evaluation
timeFrame: 18 months
measure: Efficacy: Radiological evaluation
timeFrame: 18 months
measure: Safety: Adverse events
timeFrame: 18 months
measure: Safety: Acute inflammatory events
timeFrame: 18 months
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: La Paz University Hospital. Orthopedic Surgery and Traumatology Department, Knee Unit; Cell Therapy Laboratory.
Study officials:
affiliation: Orthopedic Surgery and Traumatology Department. Knee Unit
name: Alonso C. Moreno Garcia, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994 Oct 6;331(14):889-95. doi: 10.1056/NEJM199410063311401.
citation: Wakitani S, Imoto K, Yamamoto T, Saito M, Murata N, Yoneda M. Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthritis Cartilage. 2002 Mar;10(3):199-206. doi: 10.1053/joca.2001.0504.
citation: Garcia-Gomez I, Elvira G, Zapata AG, Lamana ML, Ramirez M, Castro JG, Arranz MG, Vicente A, Bueren J, Garcia-Olmo D. Mesenchymal stem cells: biological properties and clinical applications. Expert Opin Biol Ther. 2010 Oct;10(10):1453-68. doi: 10.1517/14712598.2010.519333.