Microfragmented Adipose Tissue Versus Platelet-rich Plasma for Knee Osteoarthritis: a Randomized Comparative Trial

Study Overview
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Brief Summary
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The study aims to conduct a randomized trial comparing the clinical outcomes of PRP (standard intervention) versus Microfragmented adipose tissue (investigational) for the treatment of knee osteoarthritis. Hypothesis: Both interventions will result in significant improvement in patient-reported outcomes. We hypothesize that Microfragmented adipose tissue will provide superior outcomes.

Detailed Description
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Background Knee osteoarthritis is a leading cause of disability worldwide. Standard of care treatments for knee OA include activity modification, weight loss, therapeutic exercise and injections like corticosteroids and viscosupplement. These commonly used non-operative treatments focus on symptom palliation, but are not disease modifying. Orthobiologics have emerged as a promising treatment for knee OA. The most widely studied orthobiologic is platelet-rich plasma (PRP). PRP is a dense concentration of platelets derived from autologous whole blood and platelets are concentrated 2-5x compared to baseline. The platelets have demonstrated anti-inflammatory and chondroprotective properties.6 PRP has been shown superior to placebo and viscosupplement for knee OA in several clinical trials. While PRP is the most widely studied and used orthobiologic, it contains only platelets. Therefore, a simple, office-based intervention able to collect additional reparative cells to treat knee OA would be ideal. Adipose (fat) is a known source of reparative cells like pericytes and it can be easily and safely aspirated in the clinic. The adipose tissue aspiration and processing is accomplished through a simple process. After local anesthesia to the site of adipose aspiration (lower abdomen or buttock), 30ml of adipose is aspirated through a cannula. That adipose is then processed in accordance with FDA guidelines including minimal manipulation to remove oils.. Using minimally manipulated Microfragmented adipose tissue has been shown safe for use as injection therapy for knee OA for 3 years. Methods: Patients / Outcome Measures / Sample size: Patients with unilateral symptomatic knee OA will be recruited from the sports medicine and orthopedics clinics, as well as advertising flyers within the clinic. All patients' first visit will include a medical evaluation and assess best treatment plan for that patient, regardless of candidacy for this study. This evaluation includes x-rays of their knees as a standard part of the evaluation. If they meet criteria and choose to enroll, they will be randomly assigned to either the PRP or Microfragmented adipose tissuetreatment group. Patients will complete follow up visits and surveys at defined time points through 12 months.

Official Title
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Microfragmented Adipose Tissue Versus Platelet-rich Plasma for Knee Osteoarthritis: a Randomized Comparative Trial

Conditions
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Osteoarthritis, Knee, Microfragmented Adipose Tissue, Platelet-Rich Plasma

Intervention / Treatment
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* Device: Platelet Rich Plasma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 25-75 years BMI < 40 Diagnosis of knee OA (primary and post-traumatic) Radiographic evidence of OA of the target knee (Kellgren-Lawrence grades 1-4) Continued OA pain in the target knee despite at least 6 weeks of 1 of the following nonoperative treatments: activity modification, weight loss attempt, physical therapy, or NSAID / acetaminophen. Knee Osteoarthritis Outcomes Score (KOOS)-Pain subscale 20-65 Working knowledge of English language (to be able to complete all outcome scores) Ability to attend all follow-up appointments Exclusion Criteria: Isolated patellofemoral OA 3+ effusion of the target knee (stroke test grading system) Significant (10 degree) valgus or varus deformities Prior injection therapy: Steroid injection in target knee in the last 3 months Viscosupplementation in target knee in the last 6 months PRP in the target knee in the last 1 year No other cellular treatments in index knee (bone marrow, amniotic suspensions etc) all time Participation in any experimental device or drug study within 1 year before screening visit Oral or IM steroids for last 3 months Medical condition that may impact outcomes of procedure including: anemia thrombocytopenia bleeding disorders inflammatory disorders like rheumatoid arthritis, lupus diabetes any history of cancer (other than non-melanoma skin malignancies) taking anticoagulants (aspirin, Plavix, eliquis, Xarelto, warfarin, lovenox) Taking immunosuppressants, having a severe systemic infection Previous cartilage repair procedure on the injured cartilage surface (ie, OATS, ACI, MFX) Previous surgery at the target knee within the past 1 year Any degree of cognitive impairment. OA of either hip Pregnancy, lactating, or intent to become pregnant during treatment period Gout History of infection or current infection at the affected joint Smoking

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two-treatment parallel-design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Platelet Rich Plasma<br>157cc of whole blood will be harvested via standard venipuncture from the antecubital fossa and mixed with 24cc ACD-A (manufacturer recommends 8cc ACD-A per 52cc of whole blood). 156ml of whole blood will be processed in the FDA Cleared Angel cPRP system at 2% hematocrit. 1ml of whole blood and the resultant PRP will be analyzed in the Sysmex XN-350 for complete analysis (platelet, leukocyte, red blood cell counts). The remaining PRP will be injected under sterile technique using ultrasound-guidance through a superolateral approach. For patient comfort, 2cc of 1% lidocaine can be administered using a 26-gauge needle (into soft tissues only). PRP will then be injected using a 25-guage needle. A maximum of 6ml of PRP will be injected. Injection site will be cleaned and bandaged and patient will be dismissed with post-injection precautions and 1 month follow-up scheduled. | Device: Platelet Rich Plasma<br>* Platelet rich plasma: 157cc of whole blood will be collected, processed, and injected into the knee joint under sterile technique using ultrasound-guidance. Microfragmented adipose tissue: Adipose will be aspirated from the subcutaneous tissue of the buttock or abdomen, processed, and injected into the knee joint under sterile technique using ultrasound-guidance.<br>* Other names: Microfragmented adipose tissue;|
| Active Comparator: Microfragmented adipose tissue<br>Adipose is aspirated from the subcutaneous tissue of the buttock or abdomen. Aspiration site is injected with 10ml 1% lidocaine with epinephrine. A small poke incision is made with an 11-blade scalpel. Then 120ml of Klein solution is injected into the adipose tissue. Solution sits for 15 minutes to allow for adequate anesthesia. Aspiration cannula is inserted and moved in a back and forth motion for 2 minutes to allow for adipose aspiration. 30ml fat will be aspirated. Aspiration site is cleaned and bandaged. The aspirated fat is processed using the Lipogems system. 30ml of adipose is transferred to the device, saline is run through the device to remove oils and then approximately 5-7ml of adipose tissue is removed and ready for injection. The Microfragmented adipose tissue are then injected in identical fashion to the PRP above. | Device: Platelet Rich Plasma<br>* Platelet rich plasma: 157cc of whole blood will be collected, processed, and injected into the knee joint under sterile technique using ultrasound-guidance. Microfragmented adipose tissue: Adipose will be aspirated from the subcutaneous tissue of the buttock or abdomen, processed, and injected into the knee joint under sterile technique using ultrasound-guidance.<br>* Other names: Microfragmented adipose tissue;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| KOOS Pain [Knee Injury and Osteoarthritis Outcome Score] | The Knee injury and Osteoarthritis Outcome Pain Score [KOOS questionnaire] is a self-reported outcome measure assessing the patient's opinion about the pain in their knee. Standardized answer options are given [5 Likert boxes] and each question is assigned a score from 0 to 4. A normalized score [100 indicating no pain and 0 indicating extreme pain] is calculated. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VAS [Visual Analog Pain Scale] Pain Score | The visual analog pain scale [VAS] is a validated, subjective measure for acute and chronic pain. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between 0 [no pain] and 10 [worst pain]. | Baseline, 1 month, 3 months, 6 months, and 12 months | 
| Tegner Activity Scale | The Tegner activity scale is a one-item score that graded activity based on work and sports activities on a scale of 0 to 10. Zero represents disability because of knee problems and 10 represents national or international level soccer. | Baseline, 1 month, 3 months, 6 months, and 12 months |