Microfracture Versus Adipose Derived Stem Cells for the Treatment of Articular Cartilage Defects

Degenerative Lesion of Articular Cartilage of Knee Clinical Trial

Official title:

Randomized Controlled Trial of Microfracture Versus Adipose Derived Stem Cells for the Treatment of Isolated Articular Cartilage Defects

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02090140
• Other study ID #: 19-2838
• Status: Recruiting
• Phase: N/A
• Start date: November 2015
• Est. completion date: December 2025

Study information

• Verified date: April 2024
• Source: University of Colorado, Denver
• Contact: Kaitlyn Whitney
• Phone: (720) 872-4836
• Email: Inverness.clinicaltrials[@]cuanschutz.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 17
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Degenerative Lesion of Articular Cartilage of Knee
• Fractures, Stress

Intervention

Procedure:
• ADSC Application
Patients will undergo arthroscopic resection of approximately 5cc of the infrapatellar fat pad, which will be collected for processing for a population of ADSCs. Patients will undergo arthroscopy and preparation of the chondral defect and removal of the calcified cartilage layer. Tisseel Fibrin glue will be placed at the base of the defect side, followed by the application of the acellular collagen dermal matrix, ADSCs, and an additional layer of fibrin glue.
• Microfracture
Microfracture surgery is the standard of care for articular cartilage lesions. Patients will undergo arthroscopy with standard technique of microfracture preparation, including the creation of vertical, stable defect edges and removal of the calcified cartilage layer. A microfracture awl will then be used to perform the microfracture technique (6mm below the subchondral plate).

Locations

Country	Name	City	State
United States	UC Health Steadman Hawkins Clinic - Denver Inverness	Denver	Colorado
United States	Stanford Medical Outpatient Center	Redwood City	California
United States	Kerlan Jobe Orthopedic Institute	Santa Monica	California

Sponsors (3)

Lead Sponsor	Collaborator
University of Colorado, Denver	Stanford University, University of Kentucky

Country where clinical trial is conducted

United States, 

References & Publications (10)

Bedi A, Feeley BT, Williams RJ 3rd. Management of articular cartilage defects of the knee. J Bone Joint Surg Am. 2010 Apr;92(4):994-1009. doi: 10.2106/JBJS.I.00895. — View 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. — View Citation

Dragoo JL, Samimi B, Zhu M, Hame SL, Thomas BJ, Lieberman JR, Hedrick MH, Benhaim P. Tissue-engineered cartilage and bone using stem cells from human infrapatellar fat pads. J Bone Joint Surg Br. 2003 Jul;85(5):740-7. — View Citation

English A, Jones EA, Corscadden D, Henshaw K, Chapman T, Emery P, McGonagle D. A comparative assessment of cartilage and joint fat pad as a potential source of cells for autologous therapy development in knee osteoarthritis. Rheumatology (Oxford). 2007 Nov;46(11):1676-83. doi: 10.1093/rheumatology/kem217. Epub 2007 Sep 26. — View 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. — View Citation

Knutsen G, Engebretsen L, Ludvigsen TC, Drogset JO, Grontvedt T, Solheim E, Strand T, Roberts S, Isaksen V, Johansen O. Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial. J Bone Joint Surg Am. 2004 Mar;86(3):455-64. doi: 10.2106/00004623-200403000-00001. — View Citation

Koh YG, Choi YJ. Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis. Knee. 2012 Dec;19(6):902-7. doi: 10.1016/j.knee.2012.04.001. Epub 2012 May 14. — View Citation

Koh YG, Jo SB, Kwon OR, Suh DS, Lee SW, Park SH, Choi YJ. Mesenchymal stem cell injections improve symptoms of knee osteoarthritis. Arthroscopy. 2013 Apr;29(4):748-55. doi: 10.1016/j.arthro.2012.11.017. Epub 2013 Jan 29. — View Citation

Ma A, Jiang L, Song L, Hu Y, Dun H, Daloze P, Yu Y, Jiang J, Zafarullah M, Chen H. Reconstruction of cartilage with clonal mesenchymal stem cell-acellular dermal matrix in cartilage defect model in nonhuman primates. Int Immunopharmacol. 2013 Jul;16(3):399-408. doi: 10.1016/j.intimp.2013.02.005. Epub 2013 Mar 13. — View Citation

Wickham MQ, Erickson GR, Gimble JM, Vail TP, Guilak F. Multipotent stromal cells derived from the infrapatellar fat pad of the knee. Clin Orthop Relat Res. 2003 Jul;(412):196-212. doi: 10.1097/01.blo.0000072467.53786.ca. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Health Scores on the KOOS Questionnaire	The Knee Osteoarthritis Outcome Score (KOOS), a standard outcome questionnaire for the assessment of health-related quality of life, will be completed.	Completed at baseline, 6 months, 12 months, and 24 months post-operatively.
Secondary	Activity Level on the Tegner Activity Scale	The Tegner Activity scale, a standard outcome questionnaire for assessment of activity levels, will be completed.	Completed at baseline, 6 months, 12 months, and 24 months post-operatively.
Secondary	Cartilage Composition Assessment by MRI Scan	Magnetic resonance imaging scans consisting of routine clinical sequences and T2 and T1p quantitative maps will be conducted. T1p and T2 mapping will be used to assess regenerative cartilage composition compared to surrounding normal cartilage, surface integrity, average cartilage thickness, and the percentage to which the defect is filled.	Assessed at baseline, 6 months, 12 months, and 24 months post-operatively.
Secondary	Functionality Scores on the Lysholm Scale	The Lysholm Scale, a standard outcome questionnaire for assessment of knee functionality, will be completed.	Completed at baseline, 6 months, 12 months, and 24 months post-operatively.
Secondary	Pain Scores on the Visual Analog Scale (VAS)	The Visual Analog Scale, a standard outcome questionnaire for assessment of pain levels, will be completed.	Completed at baseline, 6 months, 12 months, and 24 months post-operatively.
Secondary	Health Scores on Veterans-Rand (VR-12) Survey	The Veterans-Rand survey, a standard outcome questionnaire for assessment of health and quality of life, will be completed.	Completed at baseline, 6 months, 12 months, and 24 months post-operatively.