ABSTRACT
Background:Membrane-assisted autologous chondrocyte transplantation is considered the gold standard surgical technique to treat greater than two millimetresdiameter cartilage lesions in the knee in patients after conservative treatment failure. However, this technique is only available in developed countries of North America, Europe and Japan. According to Brazilian law, it is considered an advanced cell therapy product. There is currently no product of this type enabled for clinical use in Brazil. Following the request of the Brazilian regulatory agency (ANVISA), this phase 1 study was developed. The objective is to access feasibility and safety of a new membrane-assisted autologous chondrocyte product.Methods:Three participants with a larger than two millimetresarticular cartilage lesion in the distal femur or the patella, which did not improvetheir symptoms with conservative treatment, will be submitted to an arthroscopically assisted cartilage biopsy. After isolation and expansion in a good manufacturing practicesfacility, chondrocyte seeded collagen membranes will be surgically inserted in the lesion and fixed with fibrin glue. The follow-up period will last 1 year. Primary outcome will be incidence and severity of complications according to NCI-CTCAE version4.0. Secondary outcomes will be Western-Ontario McMaster Universities Osteoarthritis Indexscale, International Knee Documentation Committeesubjective scale and magnetic resonance observation of cartilage repair tissuemagnetic resonancescale. Conclusions: This study, together with previous preclinical results and international experience, will allow patients in Latin America to have access to this advanced cell therapy.Trial Registration:Brazilian registry of clinical trials RBR-6fgy76 (http://www.ensaiosclinicos.gov.br/rg/RBR-6fgy76/). Ethical approval: CAAE: 73911617.2.0000.0071.
ABSTRACT
Background:Knee osteoarthritis is a progressive degenerative joint disease and remains a leading cause of pain, physical impairment and decline in health-related quality of lifein adults. Despite its incidence being amongst the highest in chronic diseases, effective biomarkers are not available to assist in its management. The main goal of this study is to identify mediators that serve as biomarkers and investigate if the levels of these biomarkers will be correlated to the efficacy of a rehabilitation program.Methods:This is a prospective cohort study with 65 participants. Patients with mild-to-moderate symptomatic knee osteoarthritis will be recruited. The Rehabilitation Program will consist of three session/week during eight weeks. Assessment about functional evaluation will be performed before and after treatment, using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)and EuroQOL-5D(Euroquality of life -five dimension) scales, Visual Analog Scale (VAS), and physical function tests (time up and go, isometric strength testing and kinematic gait analysis). Serum levels of classical pro-inflammatory cytokines, hyaluronan and high mobility group box 1 protein(HMGB-1)will be evaluated. The primary outcome is the change in WOMAC scale from baseline to end. Statistical analyses will be used to determine correlation of physical improvement and serum biomarkers. Adverse events will be monitored throughout the study. Conclusions: This trial expect to study the correlation between the anti-inflammatory effects of rehabilitation program derived factors that may be involved in suppressing cytokine induction via suppressing HMGB-1.Trial registration:Clinicaltrials.gov -NCT02964624.