Treatment of patellofemoral osteoarthritis through the implantation of a cartilage grown from nasal cartilage cells into the knee in a controlled, multicenter study, with random distribution of patients into the experimental and control groups

Descrizione riassuntiva dello studio

Currently, there are no treatment methods clearly recommended by guidelines for patellofemoral osteoarthritis (PFOA). Most current methods focus on pain management, symptom relief, or ultimately partial or total knee replacement. However, there are no approaches aimed at rebuilding cartilage and thus healing the joint surface. With the implantation of cartilage grown from nasal cartilage cells (N-TEC), good results have already been achieved in limited cartilage defects. Initial pilot studies with osteoarthritis patients show promising results. Therefore, we plan a Phase II study with 75 patients suffering from patellofemoral osteoarthritis Iwano grade 1-3. Patients will be randomly divided into two groups, one of which will be treated with the cultivated nasal cartilage, including correction of the causes of the disease, while the other will receive standard therapy with platelet-rich plasma (PRP). Up to two years after treatment, patients will 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. We believe that treatment with the cartilage transplant will lead to better clinical outcomes (less pain) on the one hand, and on the other hand, can also restore the cartilage surface and thus lead to a longer-lasting structural improvement.

(BASEC)

Intervento studiato

In this study, there is an experimental arm (surgical treatment with N-TEC) and a comparison arm with a standard therapy (injection of platelet-rich plasma (PRP)). All patients will be informed about both treatment arms before the start of the study and will sign an informed consent if they wish to participate in the study. Then, the inclusion and exclusion criteria will be checked, and the patient will be randomly assigned to a study arm. For 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 to obtain individual nasal cartilage cells. These will first be multiplied in culture vessels, to be further 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 cartilage piece in development (N-TEC) is created, which is then implanted into the knee joint to regenerate the cartilage defect. The transplants will be implanted into the knee joint during an inpatient operation. For this purpose, accompanying causes of the disease, such as patellar instability, will also be treated or corrected through additional surgical measures. Following the operation, follow-up checks will be carried out regularly up to 24 months after the surgical procedure. For the PRP injections, blood will be drawn from the patient from which the PRP will be produced. This will be injected into the knee joint with a syringe. The PRP will be injected into the knee over three consecutive weeks. This study will be examined and monitored within a very detailed protocol. It will be conducted at seven centers in Switzerland and two centers in Germany. The study duration for each participant is approximately 2 years and concludes with the 2-year follow-up 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 suitable for the study, they will receive patient information and will be asked if they wish to participate. After the informed consent is signed, the inclusion and exclusion criteria will be checked, including a blood draw (screening), and the patients will be randomly assigned to one of the two study groups. In the case of N-TEC, an outpatient removal of a cartilage piece from the nasal septum will be performed 4 weeks before implantation into the knee. The implantation of the cultivated cartilage requires 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 take place to assess healing and the mobilization or function of the knee. Clinical and radiological (MRI, X-ray) follow-ups will occur 6 and 12 months after the operation to reassess healing and the achieved mobilization or function. 24 months after the operation, a final clinical and radiological (MRI, X-ray) check will be conducted. In the case of PRP injections, the patient will be scheduled for an injection for three consecutive weeks. No hospital stay is required. After the operation, an 18-week rehabilitation program under physiotherapeutic guidance is planned. During the visits, the following examinations will be conducted: clinical checks to assess wound healing, scar formation, possible infections, side effects, and other clinical events; patient questionnaires to determine the subjective impression of the patient regarding their health and healing status (baseline data (preoperative) + 3 visits); radiological checks using magnetic resonance imaging (MRI) to examine integration and maturation of the implant, as well as X-ray checks to examine the course (progression or regression) of osteoarthritis (baseline data + 3 visits). Blood tests will be performed before inclusion in the study (40 ml) or during the cartilage sample collection (40 ml) and before the operation (40 ml) to test for viruses (HIV, hepatitis B and C, syphilis) and to examine the parameters relevant for the operation.

(BASEC)

Malattie studiate

Knee osteoarthritis is a common cause of pain and disability in the musculoskeletal system. More than 500 million people worldwide are affected. Due to increasing life expectancy and rising obesity rates, a further increase is expected, leading to an enormous socioeconomic burden and the suffering of many patients. Recent studies suggest that knee osteoarthritis often begins in the patellofemoral compartment of the knee, that is, behind the kneecap, and can then spread to the entire joint. In approximately 39% of people with knee pain over the age of 30, this so-called patellofemoral osteoarthritis (PFOA) or patellar osteoarthritis is diagnosed. Thus, PFOA and the progression to complete osteoarthritis affecting the entire knee play a crucial role in impairing the quality of life of many people and increasing healthcare costs. Due to the lack of meaningful studies, there are still no clear, widely 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 available. Although 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. Additionally, an increasing number of younger people suffer from PFOA, for whom a prosthesis is not an ideal therapy due to limited durability. Studies have shown that in patients under 55 years of age, the likelihood of reoperation is significantly increased. Therefore, a treatment option is needed that can delay artificial joint replacement with its potential disadvantages. Cell-based therapies, which are already used for cartilage repair, do not have approval for use in osteoarthritis and can often only be applied to patients up to 55 years old. However, many people suffering from osteoarthritis are older. Another aspect is that these therapies use joint cartilage cells that may already be impaired in the case of osteoarthritis, making it difficult to obtain healthy tissue for cell culture. In contrast, we use cells from the nasal septum, which are independent of age and taken from a site not affected by osteoarthritis. Therefore, healthy cartilage can still be grown from nasal cartilage cells even in older people and osteoarthritis patients. This cultivated cartilage tissue, called N-TEC, has already been used with very good results in over 70 patients in Phase I and II studies for the treatment of focal cartilage defects. It has also been shown that the implantation of the cells in the form of cultivated tissue leads to better clinical outcomes than the implantation of the cells merely on a membrane without pre-cultivation. Initial osteoarthritis patients treated with N-TEC show promising results. In this study, we want to treat patients with PFOA using N-TEC and investigate the effectiveness of this treatment compared to a standard technique (injections of platelet-rich plasma (PRP)). The treatment of patients with N-TEC also includes accompanying procedures aimed at correcting the causes of osteoarthritis. To adequately assess efficacy, we will include 75 patients with mild to moderate osteoarthritis (grade 1-3) in the clinical study, half of whom will be treated with N-TEC (surgical method) and the other half with PRP injections (standard therapy). All patients will then receive a rehabilitation program with physiotherapy. At defined intervals up to 2 years after treatment, patients will fill out standardized questionnaires (e.g., KOOS) tailored to people with knee problems or concerning the general quality of life of patients. The questions address pain, symptoms, limitations in daily life or sports, as well as the impact of the disease on the patient's lifestyle. In addition to these questionnaires, radiological examinations using magnetic resonance imaging (MRI) and X-rays will be conducted to determine whether the disease is progressing or regressing. We expect that therapy with the cultivated cartilage will lead to a better clinical outcome from the patient's perspective (less pain) and that we can show radiologically a structural change, meaning a restored joint surface with an integrated cartilage transplant.

(BASEC)

Sponsor

Universitätsspital Basel

(BASEC)

Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)

Commissione d'etica svizzera nord-ovest/centrale EKNZ

(BASEC)

Data di approvazione del comitato etico

10.04.2024

(BASEC)

Risultati dello studio