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

Articular Cartilage Lesion of the Femoral Condyle Clinical Trial

— ASCROD  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01399749
• Other study ID #: HLPTRA-2009-01
• Secondary ID: 2009-016628-29
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• First received: July 20, 2011
• Last updated: July 21, 2011
• Start date: September 2011
• Est. completion date: June 2012

Study information

• Verified date: July 2011
• Source: Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz
• Contact: Alonso C. Moreno Garcia, MD
• Phone: +34 917277314
• Email: alonso.moreno.garcia[@]gmail.com
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Articular Cartilage Lesion of the Femoral Condyle

Intervention

Other:
• Implantation of autologous cells
Implantation of autologous ASC or chondrocytes, 1 million per cm² lesion, covered by autologous periosteal membrane

Locations

Country	Name	City	State
Spain	La Paz University Hospital. Orthopedic Surgery and Traumatology Department, Knee Unit; Cell Therapy Laboratory.	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz

Country where clinical trial is conducted

Spain, 

References & Publications (3)

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. — View Citation

García-Gómez I, Elvira G, Zapata AG, Lamana ML, Ramírez M, Castro JG, Arranz MG, Vicente A, Bueren J, García-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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hyaline cartilage production for chondral knee lesions repair		18 months	No
Secondary	Efficacy: Clinical evolution	Changes in Clinical tests and SF-12 Health Survey over 18 months	18 months	No
Secondary	Efficacy: Functional evolution	Changes in Western Ontario-McMaster Osteoarthritis Score(WOMAC) over 18 months	18 months	No
Secondary	Efficacy: Functional evolution	Changes in Knee Society Score(KSS) over 18 months	18 months	No
Secondary	Efficacy: Histological evaluation	Hyaline cartilage production by histological methods at 18 months	18 months	No
Secondary	Efficacy: Radiological evaluation	MRI at 18 months	18 months	No
Secondary	Safety: Adverse events	Sistemic and local AEs especially attributable to implanted cells	18 months	Yes
Secondary	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	Yes