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

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

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.

Study Overview

• Status: Unknown
• Conditions: Articular Cartilage Lesion of the Femoral Condyle
• Intervention / Treatment: Other: Implantation of autologous cells

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28046
    • La Paz University Hospital. Orthopedic Surgery and Traumatology Department, Knee Unit; Cell Therapy Laboratory.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous ASC implantation; Treatment with autologous ASC	Other: Implantation of autologous cells; Implantation of autologous ASC or chondrocytes, 1 million per cm² lesion, covered by autologous periosteal membrane; Other Names: ACI
Active Comparator: Autologous Chondrocytes implantation; Treatment with autologous chondrocytes	Other: Implantation of autologous cells; Implantation of autologous ASC or chondrocytes, 1 million per cm² lesion, covered by autologous periosteal membrane; Other Names: ACI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz
• Investigators: Principal Investigator: Alonso C. Moreno Garcia, MD, Orthopedic Surgery and Traumatology Department. Knee Unit

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Anticipated): June 1, 2012
• Study Completion (Anticipated): June 1, 2012

Study Registration Dates

• First Submitted: July 20, 2011
• First Submitted That Met QC Criteria: July 21, 2011
• First Posted (Estimate): July 22, 2011

Study Record Updates

• Last Update Posted (Estimate): July 22, 2011
• Last Update Submitted That Met QC Criteria: July 21, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: Knee; Cartilage; Femoral; Articular; Chondrocytes; Adipose tissue-derived mesenchymal stem cells
• Other Study ID Numbers: HLPTRA-2009-01; 2009-016628-29 (EudraCT Number)