A Study to Compare Two Techniques for Articular Cartilage Repair: Cultured Chondrocytes Vs. Cultured BMAC
A Study to Compare Two Techniques for Articular Cartilage Repair: Cultured Chondrocytes Vs. Cultured BMAC
Study Title: A study to compare two articular cartilage repair techniques in the knee joint:
 The use of Cultured Chondrocytes Vs. Cultured bone marrow aspiration cells.

 Study hypothesis: We start with the hypothesis that both treatments are equally effective.

 Trial Design: The participating patients will be divided into two groups, each group
 receiving either one of the treatment modalities. This study will not be randomised or
 blinded. Both procedures will be done at the Spire Alexandra Hospital by Professor A. A
 Shetty, who is one half of the team that devised both techniques. The post-operative
 rehabilitation process will be the same for both groups.

 Trial Participants: All participants will be from patients attending Professor Shetty's
 clinic at the Spire Alexandra Hospital.

 Planned Sample Size: 50 patients in each group

 Follow-up duration: The participating patients will be followed up at 2 weeks, 6 weeks, 3
 months, 6 months, 1 year and 2 years following the surgery by visits to the clinic and
 assessed clinically. The surgical outcomes will be measured by by IKDC, KOOS and Lysholm
 scores; cartilage growth will be measured by the MOCART score.

 Planned Trial Period: Two to three years

 Primary Objective: To establish superiority, if any, of either procedure over the other by
 studying pain relief, cartilage growth and improvement in function.

 Primary Endpoint: At the end of the 2 year follow up for all participating patients.
BACKGROUND:

 Articular cartilage repair in the knee is aimed at young patients with area(s) of cartilage
 loss and no deformity of the knee. These patients aren't indicated for a knee replacement.
 Articular cartilage repair leads to improvement of symptoms of pain, locking and function.
 Traditionally, articular cartilage repair has always involved exposing the entire knee joint
 with an arthrotomy. This, though effective, would lead to a large scar, longer hospital stay,
 longer rehabilitation and its associated complications. Also, the use of Bone Marrow Aspirate
 Cells (BMAC) for the purpose of cartilage repair has long been debated with both sides having
 valid arguments and good surgical results.

 RATIONALE:

 In our study, one method (Cultured Chondrocytes) requires an arthroscopy and an arthrotomy,
 takes 6 weeks to complete and is followed by 6 weeks of partial weight bearing on the
 operated leg. The other method (Cultured BMAC) is done arthroscopically, followed by 4
 injections into the affected knee and takes 6 weeks to complete which includes 6 weeks of
 partial weight bearing on the operated leg.

 Both procedures have shown encouraging results in terms of pain relief, cartilage growth and
 improved function. The use of cultured chondrocytes requires two surgeries and takes a total
 of 12 weeks till the patient can walk without support while the use of cultured BMAC involves
 only one surgery and can have the patient walking unsupported in 6 weeks. This study aims to
 ascertain if either technique is superior to the other.

 If the cultured BMAC technique is shown to be superior, it could mean lesser surgery and
 faster recovery for the patient.

 STUDY DESIGN: This study aims to compare two techniques of articular cartilage repair in the
 knee, namely the use of cultured chondrocytes and the use of cultured bone marrow aspirate
 cells (BMAC). The principal objective of is to ascertain and assess the superiority, if any,
 of either surgical technique over the other. The superiority will be assessed with by the
 certain scoring systems (IKDC, KOOS, Lysholm and MOCART) measured pre- and post-operatively.

 Depending on which procedure the patient chooses to have, they will be allotted to either the
 cultured chondrocytes group or the cultured BMAC group. The patient is followed up in the
 clinic at the Spire Alexandra Hospital at 2 weeks, 6 weeks, 3 months, 6 months, 1 year and 2
 years following the surgery and their progress is documented by questionnaires and clinical
 examination. MRI scans are done at one and two years to assess the extent of cartilage
 growth.

 SURGICAL TECHNIQUES

 Cultured chondrocytes:

 This method has two stages. In the first stage, a knee arthroscopy is done to harvest viable
 cartilage cells which are then sent to a lab to be cultured for 6 weeks. The entry ports are
 then closed and the knee is covered with a sterile dressing. The patient is transferred to
 the surgical recovery ward and, when medically stable, then transferred to their room on the
 ward. After discharge from the hospital, the patient is advised partial weight bearing on the
 operated leg for six weeks after the surgery. They also undergo five sessions of
 physiotherapy. Surgical clips and sutures are removed at 2 weeks following the surgery.

 In the second stage, an arthrotomy is performed. The area of cartilage deficiency is prepared
 and the cultured cells are transplanted onto it. The incision is then closed and the knee is
 covered with a sterile dressing. The patient is transferred to the surgical recovery ward
 and, when medically stable, then transferred to their room on the ward. After discharge from
 the hospital, the patient is advised partial weight bearing on the operated leg for 6 weeks
 after the surgery. They also undergo 5 sessions of physiotherapy. Surgical clips and sutures
 are removed at 2 weeks following the surgery.

 Cultured BMAC:

 This method also has two major stages. The first stage involves harvesting BMAC from the
 patient's iliac crest (hip bone), which are then sent to the laboratory for culture for 3
 weeks. Simultaneously, an arthroscopy is performed on the affected knee and the area of
 cartilage deficiency is debrided and microfractured. The entry ports are then closed and the
 knee is covered with a sterile dressing. The patient is transferred to the surgical recovery
 ward and, when medically stable, then transferred to their room on the ward. After discharge
 from the hospital, the patient is advised partial weight bearing on the operated leg for six
 weeks after the surgery. They also undergo five sessions of physiotherapy. Surgical clips and
 sutures are removed at 2 weeks following the surgery.

 In the second stage, the cultured BMAC are injected into the affected knee and cells attach
 themselves to the microfractured area. The patient is then recalled at 4, 5 and 6 weeks from
 the first stage for an injection of Hyaluronic Acid into the operated knee.

 Follow up: Patients in both arms will be followed up at 2,6,12,26,52 and 104 weeks following
 the end of the second stage of the procedure. Parameters noted will be pain relief,
 improvement in function and cartilage growth as assessed by MRI scans at one and two years.
Inclusion Criteria:

 -  Participant is willing and able to give informed consent for participation in the
 study.

 -  Male or Female, aged 18 years to 65 years.

 -  Diagnosed with articular cartilage defect in the knee (ICRS/Outerbridge grade III/IV
 cartilage lesions as assessed on MRI scan).

 -  No other significant medical co-morbidities, as assessed by pre-operatively, that
 could interfere with surgery results of trial eg. Hypertension, COPD etc.

 -  Participant has clinically acceptable laboratory and ECG tests at pre-assessment
 clinic.

 -  Able (in the Investigators opinion) and willing to comply with all study requirements.

 -  Up to 3 lesions of sizes 2-8 cm2

 Exclusion Criteria:

 -  Generalized and/or inflammatory arthritis

 -  Active joint inflammation

 -  More than 5 degrees of varus or valgus deformity

 -  Age below 18 and over 65 years

 -  More than 4 lesions

 -  Lesions more than 8 cm2

 -  Significant co-morbidities or classified as ASA grade 3/4