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

Pain Clinical Trial

— PRP  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05160441
• Other study ID #: WRNMMC-2021-0345
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 26, 2022
• Est. completion date: March 31, 2025

Study information

• Verified date: June 2024
• Source: Walter Reed National Military Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: March 31, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Corticosteroid
• Osteoarthritis
• Osteoarthritis of the Shoulder
• Pain
• PRP

Intervention

Biological:
• Platelet Rich Plasma Injection
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.
• Corticosteroid Injection
5cc Normal Saline + 2cc 10 mg/ml Triamcinolone Acetonide (Kenalog)
• Delayed Platelet Rich Plasma Injection After Corticosteroid Injection Failure
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.

Locations

Country	Name	City	State
United States	Walter Reed National Military Medical Center	Bethesda	Maryland

Sponsors (4)

Lead Sponsor	Collaborator
Walter Reed National Military Medical Center	Brooke Army Medical Center, Uniformed Services University of the Health Sciences, United States Naval Medical Center, San Diego

Country where clinical trial is conducted

United States, 

References & Publications (18)

Centeno CJ, Al-Sayegh H, Bashir J, Goodyear S, Freeman MD. A prospective multi-site registry study of a specific protocol of autologous bone marrow concentrate for the treatment of shoulder rotator cuff tears and osteoarthritis. J Pain Res. 2015 Jun 5;8:269-76. doi: 10.2147/JPR.S80872. eCollection 2015. — View Citation

Cole BJ, Karas V, Hussey K, Pilz K, Fortier LA. Hyaluronic Acid Versus Platelet-Rich Plasma: A Prospective, Double-Blind Randomized Controlled Trial Comparing Clinical Outcomes and Effects on Intra-articular Biology for the Treatment of Knee Osteoarthritis. Am J Sports Med. 2017 Feb;45(2):339-346. doi: 10.1177/0363546516665809. Epub 2016 Oct 21. Erratum In: Am J Sports Med. 2017 Apr;45(5):NP10. — View Citation

Fitzpatrick J, Bulsara M, Zheng MH. The Effectiveness of Platelet-Rich Plasma in the Treatment of Tendinopathy: A Meta-analysis of Randomized Controlled Clinical Trials. Am J Sports Med. 2017 Jan;45(1):226-233. doi: 10.1177/0363546516643716. Epub 2016 Jul 21. — View Citation

Gosens T, Peerbooms JC, van Laar W, den Oudsten BL. Ongoing positive effect of platelet-rich plasma versus corticosteroid injection in lateral epicondylitis: a double-blind randomized controlled trial with 2-year follow-up. Am J Sports Med. 2011 Jun;39(6):1200-8. doi: 10.1177/0363546510397173. Epub 2011 Mar 21. — View Citation

Hak A, Rajaratnam K, Ayeni OR, Moro J, Peterson D, Sprague S, Bhandari M. A Double-Blinded Placebo Randomized Controlled Trial Evaluating Short-term Efficacy of Platelet-Rich Plasma in Reducing Postoperative Pain After Arthroscopic Rotator Cuff Repair: A Pilot Study. Sports Health. 2015 Jan;7(1):58-66. doi: 10.1177/1941738114548413. — View Citation

Hall MP, Band PA, Meislin RJ, Jazrawi LM, Cardone DA. Platelet-rich plasma: current concepts and application in sports medicine. J Am Acad Orthop Surg. 2009 Oct;17(10):602-8. doi: 10.5435/00124635-200910000-00002. Erratum In: J Am Acad Orthop Surg. 2010 Jan;18(1):17A. — View Citation

Kesikburun S, Tan AK, Yilmaz B, Yasar E, Yazicioglu K. Platelet-rich plasma injections in the treatment of chronic rotator cuff tendinopathy: a randomized controlled trial with 1-year follow-up. Am J Sports Med. 2013 Nov;41(11):2609-16. doi: 10.1177/0363546513496542. Epub 2013 Jul 26. — View Citation

Kon E, Filardo G, Delcogliano M, Presti ML, Russo A, Bondi A, Di Martino A, Cenacchi A, Fornasari PM, Marcacci M. Platelet-rich plasma: new clinical application: a pilot study for treatment of jumper's knee. Injury. 2009 Jun;40(6):598-603. doi: 10.1016/j.injury.2008.11.026. Epub 2009 Apr 19. — View Citation

Kon E, Filardo G, Drobnic M, Madry H, Jelic M, van Dijk N, Della Villa S. Non-surgical management of early knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2012 Mar;20(3):436-49. doi: 10.1007/s00167-011-1713-8. Epub 2011 Oct 25. — View Citation

Monto RR. Platelet-rich plasma efficacy versus corticosteroid injection treatment for chronic severe plantar fasciitis. Foot Ankle Int. 2014 Apr;35(4):313-8. doi: 10.1177/1071100713519778. Epub 2014 Jan 13. — View Citation

Randelli PS, Arrigoni P, Cabitza P, Volpi P, Maffulli N. Autologous platelet rich plasma for arthroscopic rotator cuff repair. A pilot study. Disabil Rehabil. 2008;30(20-22):1584-9. doi: 10.1080/09638280801906081. — View Citation

Sampson S, Reed M, Silvers H, Meng M, Mandelbaum B. Injection of platelet-rich plasma in patients with primary and secondary knee osteoarthritis: a pilot study. Am J Phys Med Rehabil. 2010 Dec;89(12):961-9. doi: 10.1097/PHM.0b013e3181fc7edf. — View Citation

Sanchez M, Anitua E, Azofra J, Aguirre JJ, Andia I. Intra-articular injection of an autologous preparation rich in growth factors for the treatment of knee OA: a retrospective cohort study. Clin Exp Rheumatol. 2008 Sep-Oct;26(5):910-3. — View Citation

Sanchez M, Anitua E, Orive G, Mujika I, Andia I. Platelet-rich therapies in the treatment of orthopaedic sport injuries. Sports Med. 2009;39(5):345-54. doi: 10.2165/00007256-200939050-00002. — View Citation

Sanchez, M., Anitua, E., & Andia, I. (2005, May). Application of autologous growth factors on skeletal muscle healing. In 2nd World Congress on Regenerative Medicine. Podium Presentation.

Schwitzguebel AJ, Kolo FC, Tirefort J, Kourhani A, Nowak A, Gremeaux V, Saffarini M, Ladermann A. Efficacy of Platelet-Rich Plasma for the Treatment of Interstitial Supraspinatus Tears: A Double-Blinded, Randomized Controlled Trial. Am J Sports Med. 2019 Jul;47(8):1885-1892. doi: 10.1177/0363546519851097. Epub 2019 Jun 4. — View Citation

Tietze DC, Geissler K, Borchers J. The effects of platelet-rich plasma in the treatment of large-joint osteoarthritis: a systematic review. Phys Sportsmed. 2014 May;42(2):27-37. doi: 10.3810/psm.2014.05.2055. — View Citation

Virchenko O, Aspenberg P. How can one platelet injection after tendon injury lead to a stronger tendon after 4 weeks? Interplay between early regeneration and mechanical stimulation. Acta Orthop. 2006 Oct;77(5):806-12. doi: 10.1080/17453670610013033. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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