A Randomized, Controlled Study to Evaluate the Efficacy of Intra-articular, Autologous Adipose Tissue Injections for the Treatment of Mild-to-moderate Knee Osteoarthritis Compared to Hyaluronic Acid: a Study Protocol

Background: Osteoarthritis (OA) is a highly debilitating joint disease that causes progressive, irreversible damage to articular cartilage. OA takes a massive toll on society that has grown in recent decades, but no therapy has been shown to halt or reverse the progression of the disease. The critical need for better treatments and increased interest cellular therapies has spawned a new generation of "minimally manipulated" cell treatments. Autologous adipose tissue injections are among the most controversial of these new treatments. Despite a lack of clinical evidence, adipose tissue injections are often marketed as "stem cell" injections with wide-ranging regenerative benefits. The purpose of this study is to estimate the effect size of the treatment by comparing the efficacy of autologous fat to hyaluronic acid (HA). As a secondary aim, we will test for preliminary evidence of efficacy of autologous fat vs. HA.

Methods: This is a prospective, single-center, parallel-group, randomized, controlled trial. Participants (n = 54) will receive either a single intra-articular, ultrasound-guided injection of autologous adipose tissue or a single intra-articular, ultrasound-guided injection of HA (1:1 ratio). Outcome data will be obtained at baseline, week-6 and month-6. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain domain (WOMAC-A) will be used as the primary outcome measure. Secondary clinical outcome measures include WOMAC (full), clinical anchors (pain, function, and stiffness), and the 29-point Patient-Reported Outcomes Measurement Information System (PROMIS®) profile. We will also take synovial fluid samples and assess sway velocity using a force plate, as well as analyze excess/discard adipose tissue to gain a better understanding of how intra-articular adipose tissue injections influence the biochemical environment of the joint.

Discussion: Given the widespread use of intra-articular fat injections in the United States, it is critical that randomized, controlled human studies evaluating efficacy and biological activity be performed. This study is the first step in addressing this unmet need, but it is not without limitations. The most notable limitations of this study are its small size and lack of blinding, which predisposes the study to both investigator and participant bias.

Trial Registration: NCT03242707 // HS-17-00365 // Registration Date (First Posted): August 8, 2018.