Title: Cartilage repair by autologous chrondocyte transplantation (ACTIVE) G0200055
Funder: Department of Health and Social Care

Abstract: ACTIVE is a prospective randomised trial comparing cell grafting techniques for the repair of articular cartilage in the knee (autologous chondrocyte implantation (ACI) or matrix-induced ACI (MACI)) with standard treatments for patients who have had a failed primary treatment for chondral or osteochondral defect(s) in the knee. Injury to the articular urfaces of the knee can lead to decreased physical activity, a poorer quality of life and impaired employment prospects. Cartilage has limited capacity for self-repair and chondral damage may predispose to osteoarthritis in later life, eventually necessitating knee replacement. Currently there is no uniform approach to managing these injuries and a number of different treatments are used with varying success. Autologous chondrocyte transplantation (ACT) is a procedure in which the defect is repaired with cells prepared from the patient’s own cartilage. ACT was first used in Sweden and follow up of the patients over 9 years has revealed good or excellent results. Over 5000 patients have now been treated with ACT, mainly in the US and numerous observational studies have been reported. However conclusive evidence that ACT offers a better long-term outcome than the traditional procedures is lacking. The present proposal is for a multicentre (12 UK and 2 Norway) prospective randomised trial of ACT (conventional periosteal method or the more recently introduced collagen membrane variation) against traditional treatments (debridement, niicrofracture/drilling, mosaicplasty). The thai will be carried out with 660 patients, each with a chondral defect on the femoral condyl of’ the knee, and for whom a previous procedure has not relieved symptoms. Outcome will be assessed by validated functional knee scores (Lysholm, IKDC) and quality of life measures (SF36) at pre-set intervals over 10 years, by resource usage and days of work and by time to further surgical intervention.

Lay abstract: Within the knee joint the surface of the bones are covered with a thin layer of cartilage which protects the bone and provides a smooth articulating surface. If this cartilage is damaged, it has little capacity for self-repair as it has no blood or nerve supply. Cartilage damage in the knee often affects young people leading to decreased physical activity and impaired employment prospects. These injuries can lead to the onset of osteoarthritis and eventually knee joint replacement may be needed. There are several ways in which orthopaedic surgeons can attempt to repair cartilage defects. These include bone and cartilage grafting and carbon fibre implant. Unfortunately these can sometimes become loose with time and need further treatment. Recently alternative methods in which living cells are placed in the defect have been used in the hope that this will provide better integration and a longer life to the repair. One of the methods is to take a small piece of cartilage from a non-load bearing part of the patient’s injured knee and to prepare cartilage cells (chondrocytes) from it in the laboratory. The chondrocytes multiply in cell culture and after several weeks can be inserted into the defect. Although the procedure has been used with excellent results in Sweden for over 9 years and widely used in the USA for several years, no randomised trial has yet been completed. It is proposed to carry out a randoimsed trial of 660 patients. Half the patients will have the new procedure of chondrocyte graft and the remainder will receive the traditional treatments. At several intervals over the following 10 years the improvement to knee function will be monitored in all the patients as well as the need for any further surgery. In this way it will be possible to decide which treatment has the best long-term outcome and this will help orthopaedic surgeons in the future when deciding treatment options with their patients. On receipt of the grant we will, in conjunction with MRC Public Communication Group, host a briefing session for science writers and journalists. We currently host an Annual Research Event for the public linked with National Science Week. Future events will include the ACTIVE trial with video models ofjoint function etc. As part of Keele University we will participate in the Adult education programme on the theme ‘Knees; function, injury and repair’.

Research activity codes: 6.2 CELLULAR AND GENE THERAPIES
Health categories: MUSCULOSKELETAL