Study of New ACL Repair Mechanism Receives $6M in NIH Support

Anterior cruciate ligament (ACL) tears are common injuries in athletes and nonathletes alike. An estimated 400,000 patients each year suffer an ACL injury. Like other intra-articular tissue injuries, ACL injuries don’t heal spontaneously. The current gold standard surgical treatment — autograft ACL reconstruction — stabilizes the knee, but has a number of drawbacks. It compromises uninjured structures to obtain an autograft, results in less than satisfactory outcomes in about 20 percent of cases, and it leaves patients with a propensity to develop early posttraumatic arthritis (PTOA).

For two decades, a team lead by Martha Murray, MD, at Boston Children’s Hospital, has been researching alternatives based on use of an implanted tissue-engineered scaffold-like device that fosters healing. Successful preclinical studies led the way to two FDA-approved preliminary clinical trials (the first-in-human cohort study, BEAR I, and a small, single-center randomized control trial, BEAR II) and today, to the start of a large multicenter, blinded, randomized clinical trial.

The procedure is known as bridged-enhanced ACL repair (BEAR) and it has been shown to achieve knee stability and reduce posttraumatic osteoarthritis in early trials.

BEAR® implant is placed between torn ACL ends. Blood drawn from the patient is added. Torn ACL ends are then pulled into implant with stitches. (Photo credit: Boston Children’s Hospital)

$6M NIH grant; PI at Cleveland Clinic

The new trial, BEAR MOON, is supported by a $6 million RO1 grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health. The trial is being conducted by Cleveland Clinic’s Kurt P. Spindler, MD, Vice Chairman of Research, Orthopaedic & Rheumatologic Institute, Director of Orthopaedic Clinical Outcomes, as principal investigator with Multicenter Orthopaedic Outcomes Network (MOON) Group. Dr. Spindler is also MOON Group’s founder.

MOON was created in 2002 to enroll and longitudinally follow a large population cohort of anterior cruciate ligament reconstructions. The NIH-funded consortium includes 18 sports medicine physicians across seven sites. The group has enrolled over 3,500 ACL reconstruction patients to establish the largest level I prospective ACL reconstruction outcomes database.

The BEAR MOON study will enroll patients at The Ohio State Jameson Crane Sports Medicine Institute; Washington University Department of Orthopaedic Surgery; Rhode Island Hospital Department of Orthopaedics; Vanderbilt University Department of Orthopaedic Surgery and Cleveland Clinic Department of Orthopaedic Surgery.

“Conventional ACL repair involves replacement of the ligament with autologous tissue harvested either from the hamstring or patellar tendon,” Dr. Spindler explains. “It is a complex procedure that has a high rate of success in terms of return to sports and activities of daily living. But the failure rate is high in adolescents. There is some graft site morbidity and PTOA is not prevented.

“With some 400,000 ACL procedures performed annually in this country, BEAR has the potential to offer that novel paradigm-changing technology that prevents graft harvest morbidity and potentially delay PTOA.”

BEAR on the scene

The study is recruiting 200 patients in a 1:1 ratio, BEAR procedure to standard autograft patellar tendon reconstruction. Subjects need to be 18 and 40 years of age with a complete ACL tear. The surgery needs to take place within 50 days of injury.

“The goal is to demonstrate noninferiority of BEAR when compared to ACL reconstruction for the key outcomes of anterior-posterior (AP) knee laxity and patient reported outcome using the International Knee Documentation Committee (IKDC) validated measure,” Dr. Spindler says. Patients will be followed at six months, one and two years after surgery.

BEAR procedure

“In the BEAR procedure, we are not just stitching the ACL together,” Dr. Spindler explains. “The magic, the key to making it work, is the scaffold.”

The procedure begins with drilling small tunnels in order to place a suture into the ACL fibers and to stabilize the knee. The tissue-engineered scaffold is implanted through a small incision in the ­­­knee. Surgeons then pull the stitched ACL tibial stump into the scaffold as the knee is extended. The patient’s own blood is applied to the scaffold to provide growth factors and stimulate healing.

Patients should be able to return to normal activities in a few months and to sports in about nine months, Dr. Spindler notes, somewhat longer than conventional ACL surgery.

Expected results

Researchers expect earlier improved range of motion and knee kinematics in the short-term and no graft harvest morbidity. BEAR’s potential long-term advantage is reduced posttraumatic arthritis compared to reconstruction, which has been demonstrated in animal models. Direct costs should be comparable to today’s ACL reconstruction, but savings are conceivable as a result of reducing the rate of posttraumatic arthritis.

“Our goal in this trial is to see if we can duplicate the earlier single-center study results on a multicenter and multisurgeon level,” Dr. Spindler says. “While achieving these aims has potential to change the clinical practice of ACL surgery, the impact is potentially even greater. The availability of an FDA-approved scaffold, carrier or delivery vehicle for complex biologic therapies to tissues within joints could speed research translation in multiple areas of regenerative medicine.”

Ellen McErlean, MSN, RN, FAHA, is coordinating this study. Contact her at mcerlee@ccf.org.

This research is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, under award number R01AR074131. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.