Clinical trial NCT02984228
Conditions: Osteoarthritis Shoulder Pain
Sponsor: Hospital for Special Surgery, New York
Start date: 2014-12-01; Completion date: 2020-11-01
Enrollment: 70 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study seeks to expand the current literature in demonstrating potentially efficacious, conservative treatments in the management of glenohumeral osteoarthritis (OA) and will compare ultrasound-guided injections of hyaluronic acid vs. platelet-rich plasma. We aim to obtain information measuring potential benefits of these interventions and to observe for any adverse events.

Detailed description:
Glenohumeral OA accounts for approximately 2-5% of all chronic shoulder pain and may be classified into primary and secondary forms. Primary glenohumeral OA is caused by degenerative joint disease, inflammatory arthropathies, and neuropathic arthropathy secondary to syringomyelia or diabetes. Secondary glenohumeral OA is caused by trauma, postoperative changes after arthroscopy or capulorraphy, and osteonecrosis. Hyaluronic acid is found in synovial joint fluid and has viscoelastic, chondroprotective, and possibly anti-inflammatory properties. It has been shown to increase joint lubrication. Platelet-rich plasma contains growth factors that have been shown to promote tissue regeneration. The aim of this study is to determine whether injections of hyaluronic acid or platelet-rich plasma can be used reliably to decrease pain, restore function, and improve quality of life in patients suffering from glenohumeral OA. Patients will be randomized to receive either an injection of hyaluronic acid or an injection of platelet-rich plasma. Outcomes will be assessed via questionnaires for up to 52 weeks post-procedure.

Arms: arm 1: Patients will receive an injection of PRP. arm 2: Patients will receive an injection of hyaluronic acid.
Interventions: intervention 1: PRP intervention 2: Hyaluronic Acid intervention 3: Ultrasound
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol documents:
Prot_SAP_000.pdf: 
Title: The efficacy of ultrasound guided glenohumeral joint injections of platelet rich plasma 
(PRP) versus hyaluronic acid (HA) in the treatment of glenohumeral osteoarthritis: A 
randomized, double-blind control trial 
 
 
 
NCT: 02984228 
 
 
Document date: October 28, 2021 
 
 


Title: The efficacy of ultrasound guided glenohumeral joint injections of platelet rich plasma 
(PRP) versus hyaluronic acid (HA) in the treatment of glenohumeral osteoarthritis: A 
randomized, double-blind control trial 
Principal Investigator: Jonathan Kirschner, MD 
Condition or Intervention to be studied: Treatment of glenohumeral osteoarthritis (OA) with a 
single injection of hyaluronic acid (HA) or platelet-rich plasma (PRP). 
Research questions/specific aims: This study aimed to determine whether HA or PRP can 
decrease pain, restore function, and improve disability in patients suffering from chronic 
glenohumeral OA (both primary and secondary) that is refractory to conservative management 
(including corticosteroid injections).   
Hypothesis: PRP injections are more efficacious than HA injections in patients with chronic 
glenohumeral OA. 
Primary outcome: Shoulder Pain and Disability Index (SPADI) score, assessed at baseline and 
up to 52 weeks post-injection 
Secondary outcomes:  
1. American Shoulder and Elbow Surgeons Society Standardized Shoulder Assessment 
Form (ASES; assessed at baseline and up to 52 weeks post-injection) 
2. Current numerical rating scale pain score (assessed at baseline and up to 52 weeks post-
injection) 
3. Average numerical rating scale pain score (assessed at baseline and up to 52 weeks post-
injection) 
4. Patient satisfaction (assessed up to 52 weeks post-injection) 
5. Side effects (assessed up to 52 weeks post-injection) 
Background:  
Shoulder pain is common, making up 16% of all musculoskeletal complaints,1,2,3 with a lifetime 
prevalence as high as 50%.4,5,6 It is second only to low back pain in musculoskeletal disorders 
that present to primary care physicians.7,8 It has a high societal burden, contributing to decreased 
productivity and worker related disability,4-6, 9-11 with direct costs of 7 billion US dollars reported 
in the year 2000.3 The management and course of patients who present with shoulder pain to a 
primary care physician is concerning, with only 50% reporting full resolution in 6 months, 
increasing to only 60% after 1 year.11-14 Causes of shoulder pain include glenohumeral 
osteoarthritis, subacromial bursitis, trauma, rotator cuff tear, instability, adhesive capsulitis, or 
labral pathology. Risk factors include advanced age, history of trauma or instability, rheumatoid 
arthritis, female sex, and occupations or sports involving repetitive movements of the upper 
extremity.  
Glenohumeral OA involves degeneration of the glenoid and humeral articular surfaces, 
associated with osteophyte formation, subchondral bony changes, and synovitis.15 It accounts for 
approximately 2-5% of all chronic shoulder pain and has an increased risk among the elderly, 


patients with a history of glenohumeral subluxation, and those who participate in sports such as 
swimming, tennis, baseball, or volleyball.3 It may be classified into primary and secondary 
forms. Primary glenohumeral OA causes include degenerative joint disease, inflammatory 
arthropathies such as rheumatoid arthritis, septic arthritis, rotator cuff tear arthropathy (CTA), 
and neuropathic arthropathy secondary to syringomyelia or diabetes.16-18 Secondary causes 
include trauma, postoperative changes after arthroscopy or capsulography, and osteonecrosis due 
to underlying systemic problems such as chronic steroid or alcohol exposure.16  
Hyaluronic acid (HA), or hyaluronate, is a high molecular weight glycosaminoglycan, found in 
synovial joint fluid, with viscoelastic, chondroprotective, and possible anti-inflammatory 
properties.19 The purpose of injecting the substance intrarticularly is to promote endogenous 
hyaluronic acid growth and production, which in turn increases joint lubrication and thus, 
decreases mechanical stress of the affected joint.20 Taken as a whole, a number of studies show 
that at least a total of 3 weekly HA injections to either the subacromial space or glenohumeral 
joint, when compared to no control group or placebo improved pain and range of motion for 3 to 
6 months.20-25  However, there continues to be inconsistency in the literature in terms of 
recruitment, sample size, injection technique, whether or not image guidance was used, and what 
type of hyaluronate was used. 
Platelet rich plasma (PRP) injections involve the use of a patient’s own platelets to take 
advantage of autologous blood growth factors present to promote tissue regeneration. It is more 
widely used for the treatment of tendinopathies and popular among injured athletes,26 but is 
beginning to see potential use in the treatment of osteoarthritis.27,28 Existing research has 
suggested benefit in pain related to knee and hip osteoarthritis, but limited to no data is available 
for its effect on chronic glenohumeral osteoarthritis (both primary and secondary).29-32 
To our knowledge, no study in the literature has been conducted that compares the efficacy of 
ultrasound guided PRP and HA injections with ultrasound guidance in the treatment of chronic 
glenohumeral arthroses. 
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Neer CS II, Craig EV, Fukuda H. Cuff-tear arthropathy. J Bone Joint Surg Am. 1983;65:1232-44. 
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Nam D, et al. Rotator Cuff Tear Arthropathy: Evaluation, Diagnosis, and Treatment. J Bone Joint Surg Am. 
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Study design: Randomized controlled trial 


Enrollment target: 70 
Inclusion criteria:  
1. English speaking/literate 
2. Age 18-100 years 
3. ≥5/10 visual analog scale pain as a direct result of primary or secondary glenohumeral 
OA  
4. At least 3 months of pain after onset of symptoms that has failed conservative treatments, 
including corticosteroid steroid injection (must be 3 months after corticosteroid injection) 
5. Pre-procedure imaging of the affected glenohumeral joint 
6. Transient relief of symptoms after diagnostic intra-articular injection into the 
glenohumeral joint 
Exclusion criteria: 
1. Painful active, concurrent cervical spine conditions 
2. Current NSAID use (can be held for study) 
3. History of taking Coumadin or similar anticoagulant, have a known coagulopathy, 
bleeding dyscrasia, or platelet count <150,000/mm3 
4. Allergic reaction to poultry or previous viscosupplementation 
5. Involved in workers’ compensation or active litigation involving affected shoulder 
6. Inability to refrain from NSAID use for 5 days prior to and 6 weeks after injection 
7. History of corticosteroid injection to affected shoulder within the last 3 months 
8. History of viscosupplementation or PRP to affected shoulder within the last 6 months 
9. Presence of acute fracture 
10. History of shoulder tumor 
11. Known uncontrolled systematic illness (uncontrolled diabetes, HIV, vasculitis, 
autoimmune/inflammatory disease) 
12. Psychiatric and somatoform disorders 
Study procedures: 
1. Patients will be randomized in a 1:1 fashion to the ultrasound-guided glenohumeral HA 
alone or PRP injection treatment group. Prior to injection, patients will be asked to 
discontinue any anti-inflammatory medications for 5 days prior to treatment.  
a. HA group will receive one 6 mL injection of low molecular weight (average 
500,000-730,000 dalton) HA preparation, Hyalgan (Fidia Farmaceutici S.p.A., 
Abano Terme, Italy). Needle guidance and injection will be performed under 
ultrasound to the affected glenohumeral joint, posterior approach, by a fellowship-
trained physician. The syringe will be covered with an opaque shield to blind both 
the patient and treating physician. 
b. PRP group will undergo the same above procedure as the HA group in respect to 
ultrasound guidance, anatomic approach, and double blinding. The Harvest 
Technologies Corporation (Plymouth, MA) SmartPReP Clear PRP preparation kit 
and machine will be used to prepare the samples in accordance with manufacturer 


instructions. Venipuncture and blood collection, PRP centrifuge, final PRP 
preparation, and covering of the syringe with an opaque shield will be performed 
in a sterile manner by a trained study team member not involved in the direct care 
and management of the study subjects. Final PRP samples will aim to be 
leukocyte reduced. Prior to injection, each sample in the PRP group will be sent to 
the laboratory for hemoglobin / hematocrit, WBC, and platelet counts. 6 mL PRP 
will be injected.  
2. In order to ensure that the treating physician is blinded to the treatment study subjects 
receive, the treating physician will perform ultrasound guidance and needle placement, 
but an Interventional Spine and Sports Medicine fellow or a Physiatry attending not 
involved in the study will prepare and perform the actual injection. 
3. Post procedure: 
a. Patients will be instructed to take acetaminophen 500 mg every 6 hours 
(maximum of 3 gms) for pain relief as needed. 
b. Ice applied over the affected joint will not be allowed for 3 days and NSAIDs are 
to be avoided for at least 6 weeks after the intervention is performed due to their 
anti-inflammatory properties. 
c. Patients will be instructed to avoid taking baths and swimming in order to 
minimize risk of infection. Showers are allowed. Patients can continue their usual 
activities of daily living, as tolerated.  
d. Follow-up questionnaires will be administered at 1, 2, 3, 6, and 12 months post-
injection. 
Sample size analysis and statistical analysis plan: 
Proposed analysis: Two-way repeated measures ANOVA 
Alpha level: 0.05 
Beta or power level: 0.861 
Primary outcome variable estimate: SPADI 
Number of groups being compared: 2 
Effect size or change expected between groups: 10-point change (±15) 
Resulting number per group: 30 
Total sample size required: 70 
 
Descriptive analyses of the patient population will include reporting means (with standard 
deviations) for continuous variables and frequencies (with percentages) for discrete variables.  
Prior to initiation of inferential analyses, data will be evaluated for completeness and, for 
continuous measures, normality. Comparative differences between the study groups will be 
evaluated using independent samples t-test for continuous variables and chi-square/Fisher’s exact 
test for categorical variables. This will include comparisons of patient characteristics as well as 
baseline patient reported outcomes and all range of motion measures. Factors that do not meet 
the assumption of normality will be analyzed using the non-parametric equivalents. 
The primary outcome in this study is the total SPADI score and the longitudinal assessment of 
that score over four follow-up time points after baseline. A systematic review by Roy et al 


(Arthritis Rheum, 2009) found that the minimal clinical important difference (MCID) for 
patients with general shoulder pain ranged between 8 and 13 points. Williams et al. (J 
Rheumatol, 1995) found that changes in the SPADI score between +10 and -10 points were not 
able to distinguish between shoulder patients whose condition improved, remained the same, or 
worsened. In a similarly designed study looking at the effect of intra-articular corticosteroids and 
supervised physiotherapy, Carette et al. (Arthritis & Rheumatism, 2003) used a 10-point change 
as their MCID. Given those estimates, we calculated our sample size based on the ability to 
detect a similar 10-point change between treatment groups in the total SPADI scores. 
Group sample sizes of 25 patients in each treatment group of the study will achieve 86% power 
to detect an MCID of 10 points in the total SPADI score between groups with an estimated 
standard deviation of ±15 points in a two-way repeated measures ANOVA design with statistical 
significance set to alpha equal to 0.05. To adjust for any loss of patients due to early withdrawal, 
we will increase our sample size by 20% for group sample sizes of 30 and a total sample size of 
70 patients. All analyses will be based on an intent-to-treat model, and any missing data will be 
imputed using a last observation carried forward methodology. Mixed models will also be 
generated to adjust for any effects of potential confounding from age, sex, and other factors. 
Longitudinal assessment of the other patient reported outcomes will also be evaluated using 
similar statistical models.