Mesenchymal Stem Cells in a Clinical Trial to Heal Articular Cartilage Defects

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Asbjørn Årøen, Oslo University Hospital
ClinicalTrials.gov Identifier:
NCT00885729
First received: April 17, 2009
Last updated: October 16, 2012
Last verified: October 2012
  Purpose

The purpose of this study is to:

  • Compare the treatment efficacy of autologous mesenchymal stem cells (Mesenchymal Stem Cells) versus chondrocytes implanted in a commercial available scaffold in a human clinical trial.
  • Determine the effects of specific three months strength training program preoperatively to improve knee function and possible postpone the need of cartilage repair surgery.
  • Determine if degenerative changes occur in the knee joints following cartilage repair. This question will be investigated in the proposed clinical trial.
  • Determine the characteristics of patients treated either by surgery or by rehabilitation in a long-term follow-up (1, 5 years).

Condition Intervention Phase
Focal Articular Fullthickness Cartilage Defect of the Knee
Procedure: stem cells
Procedure: Chondrocytes
Other: Rehabilitation program
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Mesenchymal Stem Cells in a Clinical Trial to Heal Articular Cartilage Defects

Resource links provided by NLM:


Further study details as provided by Oslo University Hospital:

Primary Outcome Measures:
  • Lysholm score [ Time Frame: 2018 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Radiographics [ Time Frame: Two and five years ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • Return to work [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    Return to work one year after surgery


Estimated Enrollment: 50
Study Start Date: April 2009
Estimated Study Completion Date: July 2018
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Stem cells
Cartilage defect are treated surgical either with chondrocytes or stem cells
Procedure: stem cells
Stem cells or chondrocytes under a commercial available membrane
Procedure: Chondrocytes
Implantation of chondrocytes
Active Comparator: Rehabilitation
Active rehabilitation program
Other: Rehabilitation program
Strength exercises, neuromuscular exercises

Detailed Description:

Musculoskeletal diseases are growing in the Norwegian population and are currently the largest group of the chronic diseases (31%). Musculoskeletal diseases are the largest cause of disability on the working part of our population (49%). The most frequent problems are rheumatism, osteoarthritis and unspecific back pain. The most common known etiology is traumatic events towards the joint. Often, the degenerative development starts with a small injury to the cartilage on weightbearing surface of the joint. This leads to changes in the surrounding cartilage, indicative of degenerative joint disease or arthrosis. When the injured area becomes larger than 2 cm2, the patients seem to experience pain. Our group has shown that 11% of patients, who underwent an arthroscopy for knee pain, had a cartilage injury on weightbearing surface with depth down to bone (grade IV) (Aroen et al.).Unfortunately, articular cartilage shows a very limited capacity of healing. Several surgical techniques have been developed to fill the cartilage defects, but so far none of them have been able to produce normal cartilage Chondrocyte implantation techniques are at date the most popular treatment, but have not demonstrated their superiority to other cartilage repair techniques. Some clinical randomised studies exist though a more thorough review of the cartilage repair methods in a study by Jakobsen and coauthors verified that no conclusion could be made considering treatment options for articular cartilage injury (Jakobsen, Engebretsen, and Slauterbeck). Although the natural history of these lesions is not finally outlined it is clear that for some patients the disruption of the cartilage surface imposes disability especially for the young athlete. The clinical studies report a significant improvement from the preoperative status although full knee function is not obtained with either of the techniques available today (Bentley et al.;Brittberg et al.;Horas et al.;Knutsen et al.). The expected Lysholm score of 80 and the standard deviation tends to be large or is not reported which illustrating the considerable variation and that full knee function is not obtained (Peterson et al.).The impact of disrupting the cartilage surface to obtain chondrocytes for culturing has not gained much attention in the clinical studies using this repair method. However it is reported that adverse effects exist as a result of this harvesting of chondrocytes for culturing (Whittaker et al.). Whittaker and coauthors observed that the harvesting of chondrocytes for cell culturing and subsequent implantation in talus resulted in a mean 15 points reduction in Lysholm score in 7 out of 10 patients. Furthermore, additional even in the best hands a mean Lysholm score of 79 are obtained for a single lesion at the femoral condyle (Peterson et al.). Even though the new scaffolds seem to reduce the rate of reoperation as a result of graft hypertrophy from 21 % to 9 %, the harvesting procedure of cartilage may still contribute to the suboptimal by this approach (Bartlett et al.;Gooding et al.). Consequently, there is a need for a better causing less morbidity when harvesting. Mesenchymal stem cells (MSC) represent an alternative cell source with the potential of generating hyaline cartilage without the same adverse effects. In addition with MSC more cells will be available for culturing with the potential of treatment of larger lesions possible. Furthermore, the repair potential of mesenchymal stem cells is not expected to decrease with age indicating that also the aging athlete may benefit from a procedure based on cartilage repair with this cell source (Dressler, Butler, and Boivin). The use of mesenchymal stem cell aspirate from the iliaca crest under a periosteum flap support the view that this might be an option to treat knee cartilage defects with success, although this study also has periosteum hypertrophy as a side effect in one of the patients (Slynarski, Deszczynski, and Karpinski). The beneficial effects of this therapy has also been reported in other studies both clinical and experimental ones (Takagi et al.;Wakitani et al.;Wakitani et al.;Wakitani et al.). Thus, the current project will investigate if the similar results can be obtained with mesenchymal stem cells as with chondrocytes both delivered in a commercial available scaffold in clinical trial with patients eligible for the current treatment options.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Norwegian citizens
  • A full-thickness cartilage lesion (diameter > 15 mm, but less than 6 cm2 and Lysholm score < 75 points) located on the femoral condyle

Exclusion Criteria:

  • Patients with malignment of the knee
  • Other knee pathology such as ACL injury or a nontreated meniscus injury will not be included in the study to avoid the impact of these knee pathologies on the final results
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00885729

Locations
Norway
Oslo UniversityHospital-Ullevaal
Oslo, Norway, 0481
Sponsors and Collaborators
Oslo University Hospital
Investigators
Study Chair: Lars Engebretsen, MD,PhD Professor
  More Information

No publications provided by Oslo University Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Asbjørn Årøen, MD, Oslo University Hospital
ClinicalTrials.gov Identifier: NCT00885729     History of Changes
Other Study ID Numbers: S-0738c 2009
Study First Received: April 17, 2009
Last Updated: October 16, 2012
Health Authority: Norway:National Committee for Medical and Health Research Ethics

Keywords provided by Oslo University Hospital:
Cartilage defect
chondrocytes
mesenchymal stem cells (MSC)
femoral condyle
knee

Additional relevant MeSH terms:
Cartilage Diseases
Musculoskeletal Diseases
Connective Tissue Diseases

ClinicalTrials.gov processed this record on September 18, 2014