Intra-articular Adipose Tissue Injections for Osteoarthritis

Study Overview
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Brief Summary
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A new generation of minimally manipulated regenerative treatments are being offered at clinics across the country, but there is no strong efficacy data to support their use. The purpose of this study is to estimate the effect size of the treatment by comparing the efficacy of autologous fat to the current standard of care treatment, hyaluronic acid (HA). As a secondary aim, we will test for preliminary evidence of efficacy of autologous fat vs. HA and determine how these treatments effect the biochemical environment of the knee by comparing pre-injection and post-injection synovial fluid biomarker profiles.

Detailed Description
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In recent years, fat treatments administered for structural reconstruction, repair, or replacement are being increasingly offered at clinics across the country. These treatments contain both autologous cells that are often referred to as stem cells or MSCs and extra-cellular matrix (ECM). Cell therapies containing ECM are thought to have the following advantages over treatments prepared using enzymatic digestion: (1) preservation of the stromal vascular niche, which allows time-release of the regenerative factors; (2) release of bioactive molecules by exosomes, which have been demonstrated to be significantly greater in mechanically processed fat than enzymatically processed fat; and (3) maintenance of the structural and morphologic unit, which is thought to increase cell efficacy by making the cells more resilient to the harsh conditions in the recipient environment. Case reports investigating the use of autologous fat treatments show promise, but a number of questions remain unanswered. Agents injected into the joint tend to be quickly cleared from the body and ECM itself has the potential to produce inflammatory signals and induce osteoarthritis. This study will use a Hyaluronic acid (HA) as an active control, which is the standard of care for pain associated with osteoarthritis. The use of HA as an active control for autologous cell-based therapies is well established and is the best option given the need to aspirate fat tissue from patients who will be receiving the study treatment.

Official Title
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A Randomized, Controlled Study to Evaluate the Efficacy of Intra-articular, Autologous Adipose Tissue Injections for the Treatment of Mild-to-Moderate Osteoarthritis

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Biological: Autologous adipose tissue injection
* Drug: Hyaluronic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 45 to 75, inclusive Normal axial alignment X-ray, Kellgren-Lawrence OA grade 2 - 3, inclusive WOMAC-pain: Between 9 and 19, inclusive Willingness to participate all scheduled follow-ups Willingness to refrain from taking NSAIDs, level 2 analgesics, and opioids for the course of the study BMI < 40 Exclusion Criteria: Pregnant or lactating Intra-articular injection within 3 months of treatment Inflammatory arthritis Any disease or active drug use that significantly compromises coagulation Significant damage and/or tears of the ACL or other supporting tissues Prior knee surgery in the last 6 months in the knee that will be injected Active tobacco use Active alcohol or substance abuse within 6 months of study entry Known hypersensitivity (allergy) to hyaluronan (sodium hyaluronate) preparations Knee joint infections, skin diseases or infections in the area of the injection site Diabetes Active inhaler use Any medical condition, which in the opinion of the clinical investigator, would interfere with the treatment or outcome evaluation

Ages Eligible for Study
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Minimum Age: 45 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: Participants will be randomly assigned to receive either a single autologous fat injection or a single hyaluronic acid injection.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous adipose tissue knee injection<br>Fat will be removed from the abdomen and processed using the Lipogems device. Approximately 5ml of the microfragmented fat product will be injected into the knee joint. | Biological: Autologous adipose tissue injection<br>* 20ml to 40ml of subcutaneous adipose tissue will be aspirated from the abdomen. Adipose tissue will be processed using the Lipogems device, a closed-loop processing device used in medical procedures involving the harvesting, concentrating and transferring of autologous adipose tissue. The resulting fat product will be delivered locally via ultrasound-guided, intra-articular injection.<br>* Other names: Lipogems, Microfragmented fat;|
| Active Comparator: Hyaluronic Acid knee injection<br>Hyaluronic Acid - Synvisc-One®: A high molecular weight sodium hyaluronate (HA). HA is an FDA approved, standard of care treatment. | Drug: Hyaluronic Acid<br>* Synvisc-One® is a high molecular weight sodium hyaluronate.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The pain items of then Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC-A) | WOMAC-A is a widely used, proprietary set of standardized questionnaires used by health professionals to evaluate the condition of patients with osteoarthritis of the knee and hip, including pain. | Change from baseline WOMAC score at 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient-Reported Outcomes Measurement Information System 29-item (PROMIS®-29) | A collection of 4-item short forms assessing anxiety, depression, fatigue, pain interference, physical function, sleep disturbance, and ability to participate in social roles and activities as well as a single pain intensity item. | Change from baseline in PROMIS-29 from baseline to 6 months | 
| Western Ontario and McMaster Universities Osteoarthritis Index | WOMAC is a widely used, proprietary set of standardized questionnaires used by health professionals to evaluate the condition of patients with osteoarthritis of the knee and hip, including pain, stiffness, and physical functioning of the joints. | Change from baseline in PROMIS-29 from baseline to 6 months | 
| Clinical Anchors | Clinical anchors will be used to identify minimal important differences in treatment groups | Clinical anchors from baseline to 6 months |