Autologous Mesenchymal Stem Cells vs. Chondrocytes for the Repair of Chondral Knee Defects - Full Text View

Purpose

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.

Condition	Intervention	Phase
Articular Cartilage Lesion of the Femoral Condyle	Other: Implantation of autologous cells	Phase 1 Phase 2

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

Further study details as provided by Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz:

Primary Outcome Measures:

Hyaline cartilage production for chondral knee lesions repair [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Efficacy: Clinical evolution [ Time Frame: 18 months ] [ Designated as safety issue: No ]
Changes in Clinical tests and SF-12 Health Survey over 18 months
Efficacy: Functional evolution [ Time Frame: 18 months ] [ Designated as safety issue: No ]
Changes in Western Ontario-McMaster Osteoarthritis Score(WOMAC) over 18 months
Efficacy: Functional evolution [ Time Frame: 18 months ] [ Designated as safety issue: No ]
Changes in Knee Society Score(KSS) over 18 months
Efficacy: Histological evaluation [ Time Frame: 18 months ] [ Designated as safety issue: No ]
Hyaline cartilage production by histological methods at 18 months
Efficacy: Radiological evaluation [ Time Frame: 18 months ] [ Designated as safety issue: No ]
MRI at 18 months
Safety: Adverse events [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
Sistemic and local AEs especially attributable to implanted cells
Safety: Acute inflammatory events [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
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

Estimated Enrollment:	30
Study Start Date:	September 2011
Estimated Study Completion Date:	June 2012
Estimated Primary Completion Date:	June 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Name: 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 Name: ACI

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

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01399749

Contacts

Contact: Alonso C. Moreno Garcia, MD	+34 917277314	alonso.moreno.garcia@gmail.com
Contact: Fernando de Miguel	+34 912071022	fdemiguel.hulp@salud.madrid.org

Locations

Spain
La Paz University Hospital. Orthopedic Surgery and Traumatology Department, Knee Unit; Cell Therapy Laboratory.	Not yet recruiting
Madrid, Spain, 28046
Principal Investigator: Alonso C. Moreno Garcia, MD
Sub-Investigator: Jose L. Leal Helmling, MD
Sub-Investigator: Santiago Bello, MD
Sub-Investigator: Fernando de Miguel, PhD
Sub-Investigator: Damian Garcia-Olmo, MD
Sub-Investigator: Mariano A. Garcia-Arranz, PhD

Sponsors and Collaborators

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

More Information

Publications:

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.

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.

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. Review.

Responsible Party:	Alonso C. Moreno Garcia, La Paz University Hospital. Orthopedic Surgery and Traumatology Department
ClinicalTrials.gov Identifier:	NCT01399749 History of Changes
Other Study ID Numbers:	HLPTRA-2009-01, 2009-016628-29
Study First Received:	July 20, 2011
Last Updated:	July 21, 2011
Health Authority:	Spain: Spanish Agency of Medicines

Keywords provided by Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz:

Cartilage
Articular
Femoral

Knee
Chondrocytes
Adipose tissue-derived mesenchymal stem cells

ClinicalTrials.gov processed this record on May 16, 2013

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