Multicenter study on the treatment of patellofemoral osteoarthritis with cultured cartilage implants compared to standard treatment

Résumé de l'étude

Currently, there are no treatment methods clearly recommended by guidelines for patellofemoral osteoarthritis (PFOA). Most methods focus on pain management, symptom relief, or partial or total knee replacement. However, there are no approaches aimed at rebuilding cartilage and thus healing the joint surface. The implantation of cartilage grown from nasal cartilage cells has already shown good results for limited cartilage defects. First patients with PFOA have also been successfully treated. In this study, we want to treat patients with varying degrees of osteoarthritis (from grade 1-4). We want to compare mild to moderate degrees of osteoarthritis (grade 1-2) with a standard treatment, AMIC. In this method, the bone is drilled to bring the stem cells from the bone marrow to the surface through the generated bleeding. The contained stem cells form a repair tissue. In this part of the study, the patient does not know which group they have been assigned to; the study is blinded. For advanced osteoarthritis (grade 3-4), there is no established treatment other than artificial joint replacement. In this group, we compare against the prosthesis and investigate whether N-TEC can relieve symptoms in the same way and thus delay or even avoid a prosthesis. The patient is informed of which study arm they have been assigned to. Overall, we want to include 150 patients, who will be randomly assigned to one of the treatment groups within grades 1-2 or grades 3-4. Up to two years after treatment, patients fill out standardized questionnaires at defined intervals to examine the impact of treatment on pain, symptoms, limitations in daily life and sports, as well as on the patient's quality of life.

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Intervention étudiée

In this study, there is an experimental arm (surgical treatment with N-TEC) and a comparison arm for each group of moderate and severe osteoarthritis with a standard therapy (mild-moderate osteoarthritis: AMIC; severe osteoarthritis: artificial joint replacement). All patients will be informed about both treatment arms before the study begins and will sign an informed consent if they wish to participate in the study. Afterward, the inclusion and exclusion criteria will be checked, and the patient will be randomly assigned to a study arm. For the treatment with the cultivated cartilage, a small piece of cartilage (7 x 7 mm) will first be taken from the nasal septum of the patient under local anesthesia on an outpatient basis. The cartilage will then be broken down in the laboratory so that individual nasal cartilage cells are available. These will first be multiplied in culture vessels to then be combined with a biodegradable material (Chondro-Gide®). In conjunction with this material, the cells begin to produce a natural cartilage matrix, so that within 2 weeks a developing piece of cartilage (N-TEC) is formed, which is then implanted into the knee joint to regenerate the cartilage defect. The grafts will be implanted into the knee joint during a stationary operation. For this, individually accompanying causes of the disease, such as patellar instability, will also be treated or corrected through supplementary surgical measures. After the operation, follow-up checks will be carried out regularly until 24 months after the surgical procedure. For the AMIC, a sham operation will be performed, in which the removal of nasal cartilage is simulated to maintain the blinding. During the knee operation, which will be performed according to clinical standard treatment, the bone will be drilled to attract blood stem cells to the surface, and the defect will then be covered with a collagen membrane (protein membrane) to promote the formation of a repair tissue. The partial prostheses will be implanted according to clinical standards. This study will be examined and monitored within a very detailed protocol. It will be conducted at two centers in Switzerland and nine centers in Europe (Italy, Croatia, Germany, Netherlands, Sweden, Poland, and Austria). The study duration for each participant is about 2 years and ends with the 2-year visit. Patients will be recruited from those who come to the regular consultation at the clinic. If it is determined during the standard diagnosis that they may be eligible for the study, they will receive patient information and will be asked if they want to participate. After the informed consent is signed, the inclusion and exclusion criteria will be checked, including a blood draw (screening), and patients will be randomly assigned to one of the two study groups. In the case of N-TEC, a small piece of cartilage will be taken from the nasal septum on an outpatient basis 4 weeks before implantation into the knee. For the AMIC, a sham operation will be performed at that time, but no cartilage will be removed. The implantation of the cultivated cartilage or the prosthesis or the performance of the AMIC will require a stay of 3-5 days in the hospital. 14 days after the operation, a first clinical check will be performed with the removal of the suture material from the skin. After 6 weeks, another clinical check will be performed to assess the healing and the mobilization or function of the knee. 6 and 12 months after the operation, clinical and radiological (MRI, X-ray) follow-ups will be performed to reassess the healing and the achieved mobilization or function. 24 months after the operation, a final clinical and radiological (MRI, X-ray) check will be performed. After the operation, a rehabilitation program is planned, which can take place under physiotherapeutic guidance as well as according to instructions via an online platform. Each patient will receive a login and thus have access to the various exercises that are appropriate for them. Feedback can also be provided to the physiotherapists via this platform. During the visits, the following examinations will be conducted: clinical checks to examine wound healing, scarring, possible infections, side effects, and other clinical events; patient questionnaires to assess the patient's subjective impression of their health and healing status (baseline data (preoperative) + 3 visits); radiological checks using magnetic resonance imaging (MRI) to examine the integration and maturation of the implant, as well as X-ray checks to examine the course (progression or regression) of the osteoarthritis (baseline data + 3 visits). Blood tests will be performed before inclusion in the study (20 ml) or at the time of cartilage sample collection (20 ml) and before the operation (20 ml) to test for infections (HIV, hepatitis B and C, syphilis) and to examine the parameters relevant for the operation.

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Maladie en cours d'investigation

Knee osteoarthritis is one of the most common causes of pain and disability. More than 500 million people are affected worldwide. Due to increasing life expectancy and rising obesity rates, a further increase is expected, leading to an enormous socioeconomic burden. Recent studies have shown that knee osteoarthritis often begins in the patellofemoral compartment of the knee, that is, behind the kneecap. In ~39% of people with knee pain over the age of 30, this so-called patellofemoral osteoarthritis (PFOA) is diagnosed. Thus, PFOA and its progression to complete osteoarthritis affecting the entire knee play a crucial role in the impairment of the quality of life for many people and the increase in healthcare costs. Due to a lack of meaningful studies, there are still no clear, generally accepted treatment recommendations in clinical guidelines for isolated PFOA. Furthermore, current therapeutic approaches are limited to pain management, symptom relief, or ultimately partial or total knee replacement, without a regenerative approach or disease-modifying treatment being available. Even though published results for joint replacement are generally satisfactory, 10-15% of patients are dissatisfied and report complications, including the progression of osteoarthritis to other areas of the knee and loosening of the joint replacement. Moreover, more and more younger people suffer from PFOA, for whom a prosthesis is not a good therapy due to limited durability. Therefore, a treatment option is needed that can delay the potential disadvantages of artificial joint replacement. Cell-based therapies, which are already used for cartilage repair, do not have approval for application in osteoarthritis and can often only be applied to patients up to 55 years old. Cartilage can also be grown from cells of the nasal septum, even in older individuals. This cultivated tissue cartilage, called N-TEC, has already been successfully used in clinical studies of phases I and II with good results for the treatment of limited cartilage defects. First osteoarthritis patients treated with N-TEC show promising results. In this study, we want to treat patients with PFOA with N-TEC. For PFOA, different severity grades from stage 1-4 are distinguished. In this study, 150 patients will initially be divided into 2 groups (stage 1-2 and stage 3-4). The first group of stage 1-2 will be treated either with N-TEC or with AMIC (Autologous Matrix-Induced Chondrogenesis). In this latter technique, the bone is drilled to bring the stem cells from the bone marrow to the surface through the generated bleeding. The area is then covered with a collagen membrane. The resulting blood clot with the stem cells then forms a repair tissue. This part of the study is blinded, meaning the patient does not know whether they are in the intervention group (N-TEC) or the control group (AMIC). For more severe osteoarthritis, this method is no longer effective. Therefore, we want to treat the group with osteoarthritis grade 3-4 with N-TEC or a (partial) knee prosthesis. The aim of this study is to find out whether the implantation of mature cartilage tissue (N-TEC) for osteoarthritis grades 1-2 leads to a higher clinical improvement than the comparison treatment (AMIC). For osteoarthritis grades 3-4, we mainly want to investigate whether N-TEC achieves the same clinical improvement as the prosthesis and whether this is also long-lasting. These data would show whether N-TEC offers the possibility to delay or even avoid the implantation of a prosthesis. Clinical outcomes will be assessed using standardized questionnaires specifically developed for patients with knee problems, which the patient will fill out themselves. The questions cover pain, symptoms, limitations in daily life and sports, as well as the patient's overall quality of life. This study can not only show whether N-TEC demonstrates the desired efficacy in PFOA but also help create better clinical treatment guidelines for PFOA.

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Sponsor

Universitätsspital Basel

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Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)

Ethikkommission Nordwest- und Zentralschweiz EKNZ

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Date d'approbation du comité d'éthique

12.12.2024

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Résultats de l'essai