Tear; Knee, Cartilage, Articular Clinical Trial
Official title:
Randomized, Multi-center Phase II Clinical Trial for the Regeneration of Cartilage Lesions in the Knee Using Nasal Chondrocyte-based Tissue (N-TEC) or Nasal Chondrocyte-based Cell (N-CAM)-Therapies
The purpose of this study is to investigate the efficacy of an engineered cartilage transplant (N-TEC) in comparison to a cell-activated matrix (N-CAM) for the treatment of articular cartilage lesions in the knee. The main innovations in this trial are the use of nasal chondrocytes and the implantation of a tissue in contrast to cells seeded on a matrix. The goals of the trial are to: (i) evaluate whether implantation of a more mature graft (tissue therapy) is beneficial for the quality and durability of the repair tissue and the clinical outcome, (ii)determine the potential of the mature graft to integrate with the adjacent cartilage and form hyaline repair tissue and (iii) assess the efficacy of each treatment in correlation to the characteristics of the defect (e.g. "acute" versus "chronic" setting).
Although cartilage damages in the joint develop mostly in older people due to degeneration of the cartilage, they also occur regularly in young people due to accidents. Especially in large cartilage defects there is no spontaneous self-healing. If these defects are left untreated, the risk of the development of osteoarthritis later on is significantly increased. However, the current treatment options for these defects involve difficult operation techniques, require tedious rehabilitation and are limited in the application for large injuries and the availability/quality of the donor material. Furthermore, they often lead to not entirely satisfactory clinical results due to the low quality of the repair tissue. In many cases permanent pain and restricted mobility persist. Even the use of the new cell therapies has not led to satisfactory results in the long term. An innovative promising approach is tissue engineering, where cartilage is manufactured in the laboratory using the body's own cells. First results of a clinical phase I study show that the use of engineered nasal cartilage for the regeneration of articular cartilage (knee joint) is feasible and safe. In addition the preliminary clinical results regarding the efficacy are also promising. The goal of this phase II clinical study is to compare the efficacy of the tissue therapy with the one of the cell therapy. In order to achieve this the investigators will enroll 108 patients in the study and divide them in two groups, one receiving the cell therapy and the other the tissue therapy. Patients must display a symptomatic, isolated cartilage lesion grade III-IV (according to the grading by the International Cartilage Repair Society (ICRS)) from 2 to 8 cm2 on the femoral condyle and/or the trochlea, have to be between 18-65 years old and must consent in oral and written manner in order to be enrolled in the study. After written informed consent has been obtained, the patients will be tested to see if they comply with all other inclusion and exclusion criteria. Subsequently blood (72ml) and a cartilage biopsy (tissue sample) from the nasal septum of the patient will be taken. The cartilage cells (Chondrocytes) are isolated from the tissue, expanded for 2 weeks and placed on a collagen matrix. For the cell therapy the resulting construct will be cultured for 2 more days to allow the cells to adhere to the matrix. For the tissue therapy the construct will be cultured for 2 more weeks, to allow the cells to form cartilage tissue. After performing the quality tests the implant will be released by the manufacturer based on the sterility, cell viability and in case of the tissue therapy product the deposition of matrix. Subsequently, the construct will be implanted in the knee. At 6 weeks as well as 3, 12 and 24 months after the operation follow-ups will be performed. During the follow-ups at 12 and 24 months questionnaires (KOOS, Euro Quality of Life (EQ)-5d) will be filled out by the patient and MRIs will be performed at 3,12 and 24 months. While the questionnaires (especially the Knee injury and Osteoarthritis Outcome Score (KOOS-Score)) provide subjective information about the efficacy of the treatment, the MRIs will shed light on the integration of the implant in the defect and give information about the quality of the repair tissue. Retrospectively the data will be analyzed in correlation to the status of the defect at time of treatment: acute (symptoms since less than 2 years) or chronic (symptoms since more than 2 years). This will give an indication whether one treatment (cell or tissue therapy) is more effective for a defined indication (acute or chronic) than the other. ;
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