Comparing Platelet Rich Plasma and Corticosteroid for Military & Civilian Patients With Glenohumeral Osteoarthritis

Study Overview
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Brief Summary
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Shoulder arthroplasty provides successful improvement in pain and function for the treatment of end stage osteoarthritis (OA) of the shoulder in the older patient population (Sanchez 2008, Sampson 2010, Kon 2012, Fitzpatrick 2017). However, the optimal non-operative treatment for shoulder OA in the young active duty and civilian populations has yet to be determined. Although corticosteroid injections (CSI) are a viable option with diagnostic and short-term therapeutic benefit in glenohumeral OA, steroid does little to address the underlying pathology and confers risk of adjacent tendon failure (Kon 2009, Gosens 2011, Monto 2014, Tietze 2014). Platelet-rich plasma (PRP) derived from autologous blood, however, has the potential to enhance soft tissue healing as previously observed in muscles and tendons (Sanchez 2005, Randelli 2008, Hall 2009). PRP contains growth factors purported to safely facilitate local tissue regeneration as corroborated in multiple clinical studies investigating tendinopathy (Virchenko 2006, Kesikburun 2013, Fitzpatrick 2017, Schwitzguebel 2019). PRP is a promising concept to bridge the gap between conventional non-operative measures and surgical arthroscopy or arthroplasty options in a high functioning patient population with refractory disease. However, clinical literature elucidating the effects of intra-articular leukocyte-poor PRP (LP-PRP) injections in large joint degenerative OA has been slower to emerge, lacking substantiated data due to small sample sizes and treatment variability. Therefore, high level evidence-based studies remain critical in ascertaining the therapeutic value and clinical efficacy of LP-PRP in glenohumeral OA in order to establish standard of care protocols and guide systematic implementation.

Detailed Description
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Shoulder arthroplasty provides successful improvement in pain and function for the treatment of end stage osteoarthritis (OA) of the shoulder in the older patient population (Sanchez 2008, Sampson 2010, Kon 2012, Fitzpatrick 2017). However, the optimal non-operative treatment for shoulder OA in the young active duty and civilian populations has yet to be determined. Although corticosteroid injections (CSI) are a viable option with diagnostic and short-term therapeutic benefit in glenohumeral OA, steroid does little to address the underlying pathology and confers risk of adjacent tendon failure (Kon 2009, Gosens 2011, Monto 2014, Tietze 2014). Platelet-rich plasma (PRP) derived from autologous blood, however, has the potential to enhance soft tissue healing as previously observed in muscles and tendons (Sanchez 2005, Randelli 2008, Hall 2009). PRP contains growth factors purported to safely facilitate local tissue regeneration as corroborated in multiple clinical studies investigating tendinopathy (Virchenko 2006, Kesikburun 2013, Fitzpatrick 2017, Schwitzguebel 2019). PRP is a promising concept to bridge the gap between conventional non-operative measures and surgical arthroscopy or arthroplasty options in a high functioning patient population with refractory disease. However, clinical literature elucidating the effects of intra-articular leukocyte-poor PRP (LP-PRP) injections in large joint degenerative OA has been slower to emerge, lacking substantiated data due to small sample sizes and treatment variability. Therefore, high level evidence-based studies remain critical in ascertaining the therapeutic value and clinical efficacy of LP-PRP in glenohumeral OA in order to establish standard of care protocols and guide systematic implementation. Although commonly used corticosteroid injections have shown some clinical benefit, there are known deleterious effects from steroid use, which include accelerated osteoarthritis progression, cartilage toxicity, and increased risk of septic arthritis. In addition to this, multiple studies demonstrate corticosteroids confers risk of adjacent tendon failure (Kon 2009, Gosens 2011, Monto 2014, Tietze 2014). There is also a concern that multiple corticosteroid injections increase the risk of fat atrophy, skin pigment changes, and tissue thinning if placed incorrectly in the more superficial tissue of the shoulder. These negative findings associated with corticosteroid injections have prompted ongoing research into alternative orthobiologic treatments that provide short to medium duration benefit for patients with osteoarthritis. Conversely, Leukocyte-Poor Platelet-Rich Plasma (LP-PRP), derived from autologous blood, has demonstrated safety and efficacy in multiple pre-clinical, randomized controlled clinical trials, and meta-analysis studies in the other large joints, causing slow acceptance in the medical community to utilize this as a treatment option, despite its increased cost compared to corticosteroid injection (Campbell 2015, Cavallo 2014, Lai 2015, Laudy 2015, Patel 2013, Smith 2016, Tietze 2014, Piuzzi 2019). However, clinical literature elucidating the effects of intraarticular leukocyte-poor PRP (LP-PRP) injections in shoulder joint degenerative OA has been slower to emerge, lacking substantiated data due to small sample sizes and treatment variability. Therefore, high level evidence-based studies remain critical in ascertaining the therapeutic value and clinical efficacy of LP-PRP in glenohumeral OA in order to establish standard of care protocols and guide systematic implementation. PRP is a promising concept to bridge the gap between conventional non-operative measures and surgical arthroscopy or arthroplasty options in a high functioning patient population with refractory disease.

Official Title
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A Prospective, Single-blind, Randomized, Multi-Center Study Comparing Platelet Rich Plasma and Corticosteroid for Patients With Glenohumeral Osteoarthritis in the Military and Civilian Population

Conditions
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Osteoarthritis of the Shoulder, Corticosteroid, PRP, Pain

Intervention / Treatment
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* Biological: Platelet Rich Plasma Injection
* Biological: Corticosteroid Injection
* Biological: Delayed Platelet Rich Plasma Injection After Corticosteroid Injection Failure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DEERS eligible Male or female, aged 18 to 70 years (inclusive) Presenting symptoms of shoulder pain caused by mild to moderate Shoulder OA as defined by Samilson Prieto criteria on a standard anterior-posterior (AP) Xray series BMI < 40 Willing and able to give voluntary informed consent to participate in this investigation Glenohumeral joint osteoarthritis that has been refractory to standard care treatments Exclusion Criteria: Patients who have received shoulder intraarticular or subacromial injection(s) in the last 3 months Patients who have undergone arthroscopic surgery on the study shoulder within the past year Patients who have undergone arthroplasty on the study shoulder Diabetes (Type 1 or II) Inflammatory arthropathies Fibromyalgia or chronic fatigue syndrome Female patient who is pregnant or nursing Patients taking narcotics Patients with planned deployment or separation from the military within 12 months Any other serious medical condition(s) that might preclude optimal outcome and/or interfere with participation such as intra-articular sepsis, bacteremia, fracture, joint instability, rheumatoid arthritis, osteoporosis, cancer, and coagulopathy Patients who have had an adverse reaction to a previous corticosteroid or PRP injection either documented in the medical record or shared by the patient during screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Platelet Rich Plasma Injection Group<br>Minimum 2cc Leukocyte Poor Platelet Rich Plasma | Biological: Platelet Rich Plasma Injection<br>* Minimum 2cc Leukocyte Poor Platelet Rich Plasma The PRP will be prepared by drawing 60cc blood from the participant through venipuncture, spinning the blood sample in a centrifuge and then injecting the platelet rich plasma (approximately 2-5cc or max collected) into the study shoulder using ultrasound guidance. This sample will be prepared by the study provider (physician assistant or physician). Any leftover blood will be safely discarded per standard protocols.<br>|
| Active Comparator: Corticosteroid Injection Group<br>5cc Normal Saline + 2cc 10 mg/ml Triamcinolone Acetonide (Kenalog) | Biological: Corticosteroid Injection<br>* 5cc Normal Saline + 2cc 10 mg/ml Triamcinolone Acetonide (Kenalog)<br>|
| Experimental: Delayed Platelet Rich Plasma Injection Group upon Corticosteroid Injection Failure<br>If a participant does not have any benefit from the corticosteroid injection by the six-week follow-up time point, then that participant will be eligible for a platelet rich plasma injection. | Biological: Delayed Platelet Rich Plasma Injection After Corticosteroid Injection Failure<br>* Participants randomized to the corticosteroid injection (CSI) group who report no improvement in their pain level at the 6 week post-CSI visit will be unblinded to their study injection (CSI) and will be offered the option to stay in the study and receive Platelet Rich Plasma injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Single Assessment Numeric Evaluation (SANE) from before injection to after injection | The SANE score is a validated patient reported outcome measure. It is a single question score that asks, how would you rate your condition today as a percentage of normal (0% to 100% scale with 100% being normal)? The SANE score is collected as standard of care. | Pre-injection (baseline) and then post-injection at 3 weeks, 6 weeks, 3 months, 6 months, 12 months, and 24 months | 
| Change in the American Shoulder and Elbow Surgeons Standardized Shoulder Form (ASES) from before injection to after injection | The ASES is a 100-point scale that consists of two dimensions: pain and activities of daily living. There is one pain scale worth 50 points and ten activities of daily living worth 50 points | Pre-injection (baseline) and then post-injection at 3 weeks, 6 weeks, 3 months, 6 months, 12 months, and 24 months | 
| Change in the Visual Analogue Scale (VAS) from before injection to after injection | A tool used to help a person rate the intensity of certain sensations and feelings, such as pain. The visual analog scale for pain is a straight line with one end meaning no pain and the other end meaning the worst pain imaginable. | Pre-injection (baseline) and then post-injection at 3 weeks, 6 weeks, 3 months, 6 months, 12 months, and 24 months | 
| Change in the Veterans RAND 12-Item Health Survey (VR-12) from before injection to after injection | The VR-12 comprises 12 questions that correspond to eight domains of health, including general health perceptions, physical functioning, role limitations because of physical problems, role limitations because of emotional problems, bodily pain, vitality, social functioning, and mental health. | Pre-injection (baseline) and then post-injection at 3 weeks, 6 weeks, 3 months, 6 months, 12 months, and 24 months | 
| Change in the Western Ontario Osteoarthritis Shoulder Index (WOOS) from before injection to after injection | The WOOS is a patient-administrated, disease-specific questionnaire for measurement of the quality-of-life of patients with osteoarthritis.7 It provides scores on four domains: (1) physical symptoms; (2) sport, recreation, and work; (3) lifestyle; and (4) emotions. Each question is answered using a visual analog scale with a possible score ranging from 0 to 100. There are 19 questions, and the total score ranges from 0 to 1900. A score of 1900 signifies that the patient has an extreme decrease in the shoulder-related quality of life, whereas a score of 0 signifies that the patient has no decrease in shoulder-related quality of life. | Pre-injection (baseline) and then post-injection at 3 weeks, 6 weeks, 3 months, 6 months, 12 months, and 24 months | 
| Change in range of motion (ROM) from before injection to after injection | Testing the range of motion (ROM) of the shoulder in different directions. If movement in a specific direction is painful or limited, this may signify that pathology is present in a specific structure of the shoulder. Common ROM tests include: forward flexion, abduction, cross-body adduction, external rotation, extension, internal rotation, scapular motion | Pre-injection (baseline) and then post-injection at 6 weeks, 3 months, 6 months, 12 months, and 24 months |