Knee Osteoarthritis
Conditions
Keywords
knee osteoarthritis, mesenchymal stem cell, adipose tissue, injection, nonoperative treatment
Brief summary
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.
Detailed 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.
Interventions
DEVICEMicrofragmented Adipose Tissue (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 most commonly from the abdomen 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. Lipogems is currently FDA-approved for orthopedic and arthroscopic procedures; thus, this would be an on-label use for knee injections.
DRUGCorticosteroid injection
Cortisone is a standard of care injection to reduce joint inflammation.
DRUGSaline
Sterile saline injection will act as a placebo group.
Sponsors
Dustin L. Richter, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
It is not feasible to blind patients who are randomized to receive Lipogems, as adipose tissue must be obtained from the participant. However, patients randomized to receive intra-articular corticosteroids or placebo injections will be blinded.
Intervention model description
This study will be conducted as a randomized, placebo-controlled clinical trial. Patients will be randomized to receive either Lipogems, intra-articular corticosteroids, or a placebo injection of saline. Lipogems is cleared for use by the FDA in orthopaedics and arthroscopy and is offered as a treatment option for knee osteoarthritis. This study will be evaluating the effectiveness (not safety) of Lipogems when compared to corticosteroids and placebo. Thus, no information will be submitted to the FDA.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Visual Analog Pain Scale (VAS) Over Time | Prior to procedure then post-procedure at 2 weeks | Scaled pain score to assess change in a patient's knee pain over time. Pain level is marked on a 100 mm line with the 0 mm corresponding to no pain and the 100 mm corresponding to 10/10 pain. Using a ruler, the score is determined by measuring the distance (mm) on the 100 mm line between the no pain anchor and the patient's mark, providing a range of scores from 0-100. The following cut points on the pain VAS have been recommended: no pain (0-4 mm), mild pain(5-44 mm), moderate pain (45-74 mm), and severe pain (75-100 mm). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Over Time | Prior to procedure then post-procedure at 2 weeks | Patient self-reported outcome measure to assess pain, stiffness, and physical function in patients with knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items), Stiffness (2 items), and Physical Function (17 items). The median is being reported for the three groups representing the change in the pain subscale. The following descriptors are used for all items: none, mild, moderate, severe, and extreme. These correspond to an ordinal scale of 0-4. The scores are summed for items in each subscale, with possible ranges as follows: pain=0-20, stiffness=0-8, physical function=0-68. A total WOMAC score is created by summing the items for all three subscales. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. The score can range from 0 to 96; however, this score is typically reported as a percentage of 100 for normalization. |
| Change in Knee Injury and Osteoarthritis Outcomes Score (KOOS) Over Time | Prior to procedure then post-procedure at 2 weeks | Patient self-reported outcome measure to assess the patient's opinion about their knee and associated issues. KOOS consists of 5 subscales; Pain, other Symptoms, Function in daily living (ADL), Function in sport and recreation (Sport/Rec) and knee related Quality of life (QOL). Standardized answer options are given (5 Likert boxes) and each question gets a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated by adding the subscales together. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Injection Patients who are randomized to the placebo group will receive an injection of 7cc of sterile saline in the affected knee.
Saline: Sterile saline injection will act as a placebo group. | 22 |
| Corticosteroid Injection 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.
Corticosteroid injection: Cortisone is a standard of care injection to reduce joint inflammation. | 23 |
| Lipogems Injection 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.
Microfragmented Adipose Tissue (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 most commonly from the abdomen 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. Lipogems is currently FDA-approved for orthopedic and arthroscopic procedures; thus, this would be an on-label use for knee injections. | 23 |
| Total | 68 |
Baseline characteristics
| Characteristic | Placebo Injection | Corticosteroid Injection | Lipogems Injection | Total |
|---|---|---|---|---|
| Age, Continuous | 61.2 years STANDARD_DEVIATION 10.8 | 56.3 years STANDARD_DEVIATION 11.5 | 62.6 years STANDARD_DEVIATION 8.4 | 60.0 years STANDARD_DEVIATION 10.5 |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Sex: Female, Male Female | 15 Participants | 14 Participants | 8 Participants | 37 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 15 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 23 | 0 / 23 |
| other Total, other adverse events | 0 / 22 | 0 / 23 | 0 / 23 |
| serious Total, serious adverse events | 0 / 22 | 0 / 23 | 0 / 23 |
Outcome results
Primary
Change in Visual Analog Pain Scale (VAS) Over Time
Scaled pain score to assess change in a patient's knee pain over time. Pain level is marked on a 100 mm line with the 0 mm corresponding to no pain and the 100 mm corresponding to 10/10 pain. Using a ruler, the score is determined by measuring the distance (mm) on the 100 mm line between the no pain anchor and the patient's mark, providing a range of scores from 0-100. The following cut points on the pain VAS have been recommended: no pain (0-4 mm), mild pain(5-44 mm), moderate pain (45-74 mm), and severe pain (75-100 mm).
Time frame: Prior to procedure then post-procedure at 2 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Injection | Change in Visual Analog Pain Scale (VAS) Over Time | 1.5 Median improvement in VAS pain score |
| Corticosteroid Injection | Change in Visual Analog Pain Scale (VAS) Over Time | 2.0 Median improvement in VAS pain score |
| Lipogems Injection | Change in Visual Analog Pain Scale (VAS) Over Time | 3.0 Median improvement in VAS pain score |
Secondary
Change in Knee Injury and Osteoarthritis Outcomes Score (KOOS) Over Time
Patient self-reported outcome measure to assess the patient's opinion about their knee and associated issues. KOOS consists of 5 subscales; Pain, other Symptoms, Function in daily living (ADL), Function in sport and recreation (Sport/Rec) and knee related Quality of life (QOL). Standardized answer options are given (5 Likert boxes) and each question gets a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated by adding the subscales together.
Time frame: Prior to procedure then post-procedure at 2 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Injection | Change in Knee Injury and Osteoarthritis Outcomes Score (KOOS) Over Time | 8 units on a scale in comparison to placeb |
| Corticosteroid Injection | Change in Knee Injury and Osteoarthritis Outcomes Score (KOOS) Over Time | 13.9 units on a scale in comparison to placeb |
| Lipogems Injection | Change in Knee Injury and Osteoarthritis Outcomes Score (KOOS) Over Time | 27.8 units on a scale in comparison to placeb |
Secondary
Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Over Time
Patient self-reported outcome measure to assess pain, stiffness, and physical function in patients with knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items), Stiffness (2 items), and Physical Function (17 items). The median is being reported for the three groups representing the change in the pain subscale. The following descriptors are used for all items: none, mild, moderate, severe, and extreme. These correspond to an ordinal scale of 0-4. The scores are summed for items in each subscale, with possible ranges as follows: pain=0-20, stiffness=0-8, physical function=0-68. A total WOMAC score is created by summing the items for all three subscales. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. The score can range from 0 to 96; however, this score is typically reported as a percentage of 100 for normalization.
Time frame: Prior to procedure then post-procedure at 2 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Injection | Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Over Time | 3.5 scores on a scale |
| Corticosteroid Injection | Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Over Time | 3.50 scores on a scale |
| Lipogems Injection | Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Over Time | 5.00 scores on a scale |