Efficacy of Micro-fragmented Adipose Tissue Injection for Knee Osteoarthritis.

Dustin L. Richter, MD

Status: Completed

Conditions: Knee Osteoarthritis

Treatments: Drug: Corticosteroid injection; Device: Microfragmented Adipose Tissue (Lipogems); Drug: Saline

Study type: Interventional

Funder types: Other

Identifiers

NCT03379168

17-146

Details and patient eligibility

About

Knee osteoarthritis (OA) causes patients considerable joint pain and leads to instability, reduced range of motion, and functional limitations. Current treatment limitations have generated interest in alternative options to restore function and alleviate joint pain, some with the aim of healing damaged articular cartilage. There has been preliminary support in the literature for reduced pain and improved functional performance in patients who receive mesenchymal stem cells (MSCs) as part of a treatment regimen. MSCs can be costly and are limited by complex regulatory issues. This interest in an alternative isolation method lead to the development of Lipogems. Lipogems is a technique to harvest, process, and inject minimally manipulated adipose tissue. This procedure is enzyme free and requires no clonal expansion or manipulation. The goal of this study is to evaluate the possible benefits of reduced joint pain and increased joint functionality in patients with knee osteoarthritis after the injection of Lipogems. In addition, given the limitations of prior research on the efficacy of intra-articular corticosteroids, the investigators will also include this as an additional study group to compare to placebo. There have been case reports published showing favorable outcomes. This would be the first study reporting data on the efficacy of Lipogems for pain relief in knee OA in a randomized, controlled clinical trial with a larger sample of patients.

The investigators hypothesize that patients who receive an injection of Lipogems will experience a decrease in pain of the affected knee and an increase in joint functionality in comparison to placebo. The investigators also hypothesize that patients who receive an intra-articular corticosteroid will experience decreased pain or improved functionality in the affected joint compared to placebo.

Full description

Objectives:

1. The purpose of this study is to evaluate the possible benefits of reduced joint pain and increased joint functionality in patients with knee osteoarthritis after the injection of Lipogems. Based on limitations of prior research, intra-articular corticosteroids are included as a study group to be evaluated for impact on pain relief and joint functionality in comparison to placebo.
2. The investigators hypothesize that patients who receive an injection of Lipogems will experience a decrease in pain of the affected knee and an increase in joint functionality in comparison to placebo. The investigators also hypothesize that patients who receive an intra-articular corticosteroid will experience decreased pain or improved functionality in the affected joint.

Background:

Osteoarthritis (OA) causes patients considerable joint pain and leads to instability, reduced range of motion, and functional limitations. Pathologic findings of OA include decreased articular cartilage, joint space narrowing, osteophytes, subchondral sclerosis and bone cysts. Currently, treatment options are confined to symptom management only. Options for treatment include: topical preparations, nonsteroidal anti-inflammatory drugs (NSAIDs), intra-articular injections, and, in severe cases, total knee arthroplasty. Review of recent recommendations shows limitations to all available treatments. Oral NSAIDs have shown relief, but is limited to patients without risk factors or contraindications. Topical NSAIDs are recommended in elderly patients or those with GI risk factors, rather than oral NSAIDs. However, pain improvement took 12 weeks and was not long-lived, potentially due to compliance issues in application. A recent systematic review of intra-articular corticosteroids reported that, due to low-quality evidence, it is inconclusive whether intra-articular corticosteroids provided any short or long-term pain relief. Taylor's review of hyaluronic acid treatment is hampered by the variability of preparations currently on the market and shortage of double-blind placebo controlled studies, but conflicting data is reported. Osteoarthritis Research Society International currently recommends corticosteroid injections for short-term pain relief only, and is inconclusive in recommending hyaluronic acid.

The aforementioned treatment limitations have generated interest in alternative options to restore function and alleviate joint pain, some with the aim of healing damaged articular cartilage. It is well known that articular cartilage is avascular and lacks innervation, which limits its intrinsic healing and repair capabilities. Chondrocytes, derived from MSCs, have limited potential to replicate, which also limits the intrinsic healing and repair capabilities of articular cartilage. The stromal vascular fraction, containing adipose derived mesenchymal stem cells (MSCs), has historically been isolated successfully via enzymatic processes. There has been preliminary support in the literature for reduced pain and improved functional performance in patients who received MSCs as part of treatment. However, approaches to isolate MSCs are costly, time consuming, require extensive lab equipment, and are currently limited by complex regulatory issues.

Thus, interest in an alternative isolation method lead to the development of Lipogems. Lipogems is a technique to harvest, process, and inject minimally manipulated adipose tissue. This procedure is enzyme free and requires no clonal expansion or manipulation. Lipoaspirate is harvested and washed in saline solution, then processed through a closed-system device that micro-fragments the adipose tissue. This mechanical process retains the vascular architecture, mature pericytes, and MSCs for autologous injection.

As new technologies are becoming available for the treatment of OA, it is important that investigators gather high-quality data on their efficacy and outcomes. The goal of this study is to evaluate the possible benefits of reduced joint pain and increased joint functionality in patients with knee osteoarthritis after the injection of Lipogems. In addition, given the limitations of prior research on the efficacy of intra-articular corticosteroids, the investigators will also include this as an additional study group to compare to placebo. Although Lipogems is relatively new to the United States, it has been used for a variety of orthopaedic arthroscopic applications overseas including the treatment of knee OA and is being used more frequently now in the United States. As of now, there are no published studies reporting the outcomes of patients who receive Lipogems for knee OA. There have been case reports published showing favorable outcomes. Thus, this would be the first study reporting data on the efficacy of Lipogems for pain relief in knee OA in a randomized, controlled clinical trial with a larger sample of patients. It would also be the only study to date comparing Lipogems to intra-articular corticosteroids and placebo injections. The investigators feel this study design will provide new insight into the efficacy of Lipogems for pain relief of symptomatic knee OA as well as offer new data on the efficacy of intra-articular corticosteroids in this application.

Enrollment: 75 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Age of eighteen or older
• Diagnosis of symptomatic knee osteoarthritis
• Radiographic evidence of knee osteoarthritis. Note: For the purposes of this study, radiographic evidence of knee osteoarthritis is defined as any one or more of the following: osteophytes, joint space narrowing, loss of articular cartilage thickness, subchondral sclerosis or cysts.

Exclusion criteria

• History of treatment with any intra-articular knee injection
• Current ligament instability as demonstrated by a positive Lachman Test, Anterior or Posterior Drawer Test, or positive Valgus or Varus Stress Test.
• Known allergy to lidocaine
• Under 18 years of age
• Pregnant women
• Prisoners

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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75 participants in 3 patient groups, including a placebo group

Placebo Injection

Placebo Comparator group

Description:

Patients who are randomized to the placebo group will receive an injection of 7cc of sterile saline in the affected knee.

Treatment:

Drug: Saline

Corticosteroid Injection

Active Comparator group

Description:

Patients who are randomized to the corticosteroid group will receive an injection of 2cc (80mg) of triamcinalone acetonide injectable suspension mixed with 5 cc of 1% plain lidocaine for a total of 7cc of fluid injected in the affected knee.

Treatment:

Drug: Corticosteroid injection

Lipogems Injection

Experimental group

Description:

Patients who are randomized to the Lipogems treatment group will undergo a lipoaspiration from their abdomen and autologous injection of the harvested adipocytes into their knee. It is standard to harvest three to four times more adipose tissue than is planned to be injected to account for tissue processing by the Lipogems device. The investigators plan to inject 7cc of autologous adipose tissue. Thus, the investigators will harvest between 25 and 30 cc of adipose tissue from each patient. The tissue will be processed immediately and 7cc will be injected. Any remaining adipose tissue will be disposed of immediately in biohazardous waste.

Treatment:

Device: Microfragmented Adipose Tissue (Lipogems)