Biologic Therapy to Prevent Osteoarthritis After ACL Injury

Recruiting now · Early Phase 1 · Has a placebo group

Conditions studied: Anterior Cruciate Ligament Injuries

In brief

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 early injection of IL-1 inhibitor (IL-1Ra) into the knee joint of patients suffering recent ACL injury will decrease the incidence of cartilage damage later in life. After appropriate IRB approval, a total of 32 active patients will be randomized into one of two treatment groups. Group 1 will receive removal of the knee joint fluid (aspiration of hemarthrosis) using a needle and syringe within 1 to 2 weeks 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 3 to 5 days after the initial injection. 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 1 to 2 weeks of ACL injury. In addition, a second knee aspiration and intra-articular administration of 150mg (\~5mls) of anakinra (rhIL-1Ra) will be performed at 3 to 5 days after the initial injection. 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 2 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 time points are optional and highly encouraged. These additional MRIs are at no cost to the patient.

Key facts

Study ID: NCT03968913
Run by: University of California, Los Angeles
People needed: 32
Starts: 2021-09-15
Expected to finish: 2027-01-30
Last updated by the study team: 2026-01-26

Who can join

Age: 18 and older, up to 35. Sex: any. Healthy volunteers: accepted.

You may qualify if…

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 2 weeks of presentation
must elect to undergo bone-patellar tendon-bone (BTB) autograft ACL reconstruction within 45 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

You may not qualify if…

injury occurring more than 2 weeks prior to enrollment
previous ipsilateral knee injury
multi-ligamentous knee injury
pre-existing or concurrent grade 3 or 4 chondral (cartilage) injuries
previous ipsilateral knee surgery (meniscus tear, ACL tear, chondral injury, etc.)
of note, concurrent acute meniscus injury is NOT an exclusion criteria
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
current malignancy
current inflammatory/rheumatologic disease
current immune-compromised state
current renal failure

Where it is running

University of California, Los Angeles — Los Angeles, California, United States (enrolling)

Full record on ClinicalTrials.gov

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