Biologic Therapy to Prevent Osteoarthritis After ACL Injury

• Status: Recruiting
• Trial end date: 2023-05-30
• Target enrollment: 0
• Participant gender: All

Summary

Anterior cruciate ligament (ACL) injuries are extremely common. On average, 50% of individuals suffering an ACL injury will develop radiographic osteoarthritis (OA) 10 to 20 years after injury. Unfortunately, ACL reconstruction does not prevent risk of future OA.

Interleukin-1 (IL-1) levels in the human knee joint increase transiently after an ACL injury. In animal experiments, if interleukin-1 levels are increased in the joint, this alone causes arthritis to occur. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring inhibitor of IL-1. However, in ACL injuries the balance of these two proteins is disturbed transiently after injury, with the effects of IL-1 dominating this balance. In a large animal model of ACL injury, injection of IL-1Ra into the knee joint after ACL injury significantly decreased the amount of arthritis that was later observed.Thus, the investigators hypothesize that injection of IL-1 inhibitor (IL-1Ra) into the knee joint of patients suffering recent ACL injury will decrease the incidence of cartilage damage.

After appropriate IRB approval, a total of 48 active patients will be randomized into one of three treatment groups. Group 1 will receive removal of the knee joint fluid (aspiration of hemarthrosis) using a needle and syringe within 1 week of injury. Following aspiration of the knee joint, an injection of 5 milliliters (mls) of sterile saline (as a placebo control) will be administered. In addition, a second knee aspiration procedure and an injection of 5mls of sterile saline into the injured knee joint will be performed at 10 days post-injury. Group 2 will receive aspiration of the knee hemarthrosis as described in group 1 as well as intra-articular administration of 150mg (~5mls) of anakinra (rhIL-1Ra) within 7 days of ACL injury. In addition, a second knee aspiration and injection of 5mls of sterile saline into the injured knee joint will be performed at 10 days post-injury. Group 3 patients will receive aspiration of the knee hemarthrosis and injection of anakinra as described in group 2 as well as a second intra-articular knee injection of anakinra (150mg, ~5mls) on post-injury day 10. Thus, all patients in this randomized placebo-controlled trial will undergo two injection procedures prior to surgery.

Investigators will analyze subjects self-reported function and pain scores as well as urinary levels of cartilage breakdown products over time. Additionally, MRI studies will be used to compare MRI findings among patients in these 3 treatment groups. Urine samples will be obtain prior to surgery, at the time of surgery and at multiple time points after surgery (3, 6, 9, 12 and 24 months after surgery). Subjective outcome measure assessments (surveys) will be completed by participants prior to surgery and then again at 6, 9, 12 and 24 months post-operatively. MRI studies will be obtained at 1 year and 2 years following surgery. Additional, MRI studies at earlier time points are optional.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of California, Los Angeles
• Collaborator: Orthopedic Research and Education Foundation
• Treatments: Interleukin 1 Receptor Antagonist Protein

Criteria

Inclusion Criteria:

• patients age 18 to 35 years with closed growth plates as visualized on plain radiographs who participate in cutting and pivoting activities.

• we will enroll an equal number of men and women in each treatment group (16 total per group; 8 men, 8 women).

• study participants must have an MRI-confirmed ACL injury within 7 days of presentation

• must elect to undergo bone-patellar tendon-bone (BTB) autograft ACL reconstruction within 30 days of injury

• no clinical or MRI evidence of posterior cruciate ligament injury

• no more than grade 1 medial collateral ligament injury

• no concurrent posterolateral corner injury to the ipsilateral knee

Exclusion Criteria:

• injury occurring more than 7 days prior to enrollment

• previous ipsilateral knee injury, multi-ligamentous knee injury

• significant (>1cm full-thickness) meniscus tear

• pre-existing or concurrent grade 3 or 4 chondral (cartilage) injuries

• previous ipsilateral knee surgery

• previous contralateral meniscal or ligamentous knee injury

• active infection

• known allergy or adverse reaction to anakinra

• intra-articular cortisone injection into either knee within 3 months of injury

• prior exposure to IL-1Ra

• participation in another clinical drug trial within the 4 weeks before injury

• history of any coagulopathy or current anti-coagulation therapy

• malignancy

• inflammatory/rheumatologic disease

• immune-compromised state

• concomitant significant meniscus pathology

• renal failure