Clinical trial NCT02090140: Microfracture Versus Adipose Derived Stem Cells for the Treatment of Articular Cartilage Defects
Official title: Randomized Controlled Trial of Microfracture Versus Adipose Derived Stem Cells for the Treatment of Isolated Articular Cartilage Defects
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Degenerative Lesion of Articular Cartilage of Knee
Keywords: cartilage/transplantation
cartilage, articular/injuries
cartilage, articular/surgery
chondrocytes/cytology
knee injuries/surgery
knee joint/surgery
orthopedic procedures/methods
tissue engineering
tissue scaffolds
arthroscopy/methods
chondrocytes/transplantation
adipose tissue/cytology
cartilage, articular/cytology
chondrogenesis/physiology
osteogenesis/physiology
stem cell transplantation/methods
stem cells
tissue engineering/methods
cartilage, articular/pathology
chondrocytes/pathology
knee joint/pathology
platelet-rich plasma
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: University of Kentucky
name: Stanford University
First posted: 2014-03-18
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare two biologic methods for the treatment of articular cartilage defects in the knee. The first method, microfracture, is the standard of care and is routinely used to recruit cells from the subchondral bone marrow to the site of cartilage loss. The second method is the application of adipose-derived stem cells (ADSCs) to the defect site. In theory, ADSCs on a collagen scaffold should enable the delivery of more specific progenitor cells to the site of injury, resulting in better regeneration and integration of articular cartilage at the site of a defect as compared to the microfracture method.

Detailed description: Patients enrolled in the ADSC cohort will undergo the following procedures: arthroscopic resection of approximately 5cc of the infrapatellar fat pad using a motorized shaver (standard use in arthroscopy). Fat will be collected in a sterile Aquavage Collection System (AV1200, MD Resources, Livermore, CA) and kept sealed until processing. Fat will then immediately be processed in the Harvest Adiprep System to separate a population of ADSCs. This system concentrates an average of 5 x 105 cells/ml. All specimens will be processed using routine sterile procedures within the operating room; cells destined for implantation will not leave the operating room. Concurrently, patients will undergo arthroscopy and similar preparation of the chondral defect and removal of the calcified cartilage layer. However, no puncture of the subchondral bone will be performed. A layer of fibrin glue (Tisseel) will be placed at the base of the defect to seal off any bleeding from the subchondral plate followed by the application of the acellular dermal matrix (Allopatch HD, MTF Corporation, Edison, NJ, USA)and ADSCs. An additional layer of Tisseel will then be applied over the cells and matrix. No additional fixation will be applied. The matrix and cells will be recessed below the articular surface by an average of 1mm.

They will then complete outcome questionnaires and additional MRI scans at 6, 12, and 24 months post-operatively.

Eligibility criteria: Inclusion Criteria:

* Must be between ages 18 and 50 years.
* Must have a discrete, contained chondral defect less than 400mm\^2 located on the medial or lateral femoral condyle
* Must have overall neutral lower limb mechanical alignment (\<5 degrees varus or valgus).

Exclusion Criteria:

* Ages younger than 18 years and older than 50 years.
* If they have undergone previous chondral procedures
* If they have pre-existing osteoarthritis (Kellegren-Lawrence Grade ≥2)
* If they have a BMI \>30.

Primary outcomes:
measure: Health Scores on the KOOS Questionnaire
timeFrame: Completed at baseline, 6 months, 12 months, and 24 months post-operatively.
Secondary outcomes:
measure: Activity Level on the Tegner Activity Scale
timeFrame: Completed at baseline, 6 months, 12 months, and 24 months post-operatively.
measure: Cartilage Composition Assessment by MRI Scan
timeFrame: Assessed at baseline, 6 months, 12 months, and 24 months post-operatively.
measure: Functionality Scores on the Lysholm Scale
timeFrame: Completed at baseline, 6 months, 12 months, and 24 months post-operatively.
measure: Pain Scores on the Visual Analog Scale (VAS)
timeFrame: Completed at baseline, 6 months, 12 months, and 24 months post-operatively.
measure: Health Scores on Veterans-Rand (VR-12) Survey
timeFrame: Completed at baseline, 6 months, 12 months, and 24 months post-operatively.
Other outcomes:
Locations:
city: Redwood City
country: United States
facility: Stanford Medical Outpatient Center
state: California
city: Santa Monica
country: United States
facility: Kerlan Jobe Orthopedic Institute
state: California
city: Denver
country: United States
facility: UC Health Steadman Hawkins Clinic - Denver Inverness
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Jason Dragoo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Seth L Sherman, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Giavaresi G, Bondioli E, Melandri D, Giardino R, Tschon M, Torricelli P, Cenacchi G, Rotini R, Castagna A, Veronesi F, Pagani S, Fini M. Response of human chondrocytes and mesenchymal stromal cells to a decellularized human dermis. BMC Musculoskelet Disord. 2013 Jan 7;14:12. doi: 10.1186/1471-2474-14-12.
citation: Desando G, Cavallo C, Sartoni F, Martini L, Parrilli A, Veronesi F, Fini M, Giardino R, Facchini A, Grigolo B. Intra-articular delivery of adipose derived stromal cells attenuates osteoarthritis progression in an experimental rabbit model. Arthritis Res Ther. 2013 Jan 29;15(1):R22. doi: 10.1186/ar4156.
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