Recruiting
Early Phase 1

Biologic Therapy

Sponsor:

UCLA

Code:

NCT03968913

Conditions

Anterior Cruciate Ligament Injuries

Eligibility Criteria

Sex: All

Age: 18 - 35

Healthy Volunteers: Accepted

Interventions

Anakinra injection

sterile saline injection

Study Details

Brief 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 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.

Conditions

Anterior Cruciate Ligament Injuries

Study ID

NCT03968913

Start date

Sep 15, 2021

Status verified date

Jan, 2026

Completion date

Jan 30, 2027

Anticipated

Primary completion date

Jan 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 35

Healthy Volunteers: Accepted

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 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

Exclusion Criteria:

  • 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

Study Design

Enrollment

32 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

placebo comparator: Control

Subjects will receive two injections of sterile saline after ACL injury, prior to surgery

active comparator: Two doses Anakinra

Subjects will receive two injections of anakinra after ACL injury, prior to surgery

Interventions

Anakinra injection

anakinra 150mg in 5milliliters of sterile saline will be injected into the knee joint

sterile saline injection

5 milliliters of sterile saline will be injected into the knee joint

Primary outcome measure

  • Cytokine level analysis of synovial fluid [ Time Frame: Synovial fluid will be collected within 2 weeks of injury and at approximately 3 to 5 days after the initial injection, at the time of surgery and approximately 10 days after surgery. ]
  • Cartilage biomarker analysis of synovial fluid [ Time Frame: Synovial fluid will be collected within 2 weeks of injury and at approximately 10 days after ACL injury, at the time of surgery and approximately 10 days after surgery. ]

Central Contacts and Locations

Central contacts

Adreanne Rivera

310.794.0213adreannerivera@mednet.ucla.edu

Locations

University of California, Los Angeles

Recruiting

Los Angeles, California, United States, 90095

Contacts

Thomas J. Kremen, M.D.

424-259-9856tjkremen@mednet.ucla.edu

Adreanne Rivera

310-794-0213adreannerivera@mednet.ucla.edu

More Information

Sponsor

University of California, Los Angeles

Last update posted

Jan 26, 2026

Last verified

Jan, 2026

Keywords

  • Osteoarthritis
  • ACL
  • Anakinra

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by University of California, Los Angeles on 2026-01-26.