Platelet-rich Plasma Injections and Physiotherapy in the Treatment of Chronic Rotator Cuff Tendinopathy

Study Overview
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Brief Summary
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The investigators aim to investigate whether combination of PRP injection with physiotherapy program could produce superior effect than either treatment alone.

Detailed Description
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Rotator cuff (RC) tears are a common source of shoulder pain and account for more than 4.5 million physician visits per year. In the overall population, the prevalence of RC tear is 20.7% and rises to 50% among patients older than 80 years. Partial-thickness and full-thickness RC tears has also been reported in 30% to 50% of the population aged older than 50 years. RC tears cause shoulder dysfunction, interfere daily activity, and may reduce quality of life. Treatment of RC tear includes surgical and conservative treatment. Considering operative risk, high possibility of re-tear after operation, and possible tendon healing with non-surgical treatment, for patients with a partial-thickness tear or a small full-thickness tear, conservative treatment is usually tried first. Previous report found that conservative treatment might be effective in 73% to 80% of cases with full-thickness tear of the rotator cuff. Conservative treatment of RC tear consists of rest, physiotherapy (including therapeutic exercise), non-steroidal anti-inflammatory drugs, and corticosteroid or hyaluronate subacromial injections. A. In addition, exercise has also been proven effective in the management of RC tear. In spite of the advanced surgical techniques and conservative methods, healing of RC tear remains problematic due to poor vascularization at the lesion site and failure to restore normal enthesis (tendon-bone junction) histology. Over past few years platelet-rich plasma (PRP) presents an attractive option to improve and accelerate healing of the rotator cuff lesion. PRP is defined as a portion of the plasma fraction of autologous blood having a platelet concentration above baseline (usually 2X to 4X). It is derived from centrifuging whole blood, and contains numerous growth factors, including platelet-derived growth factor, vascular endothelial growth factor, transforming growth factor, fibroblast growth factor, epidermal growth factor, hepatocyte growth factor, and insulin-like growth factor. Because of the increased concentration and release of growth factors, PRP can potentially enhance the recruitment and proliferation of tenocytes, stem cells, and endothelial cells. Given the autologous nature of PRP, safety concerns are minimal. Relative contraindications include patients with a history of thrombocytopenia, use of anticoagulants, tumor, metastatic disease, active infection, or pregnancy. Up to now no documented cases of carcinogenesis or tumor growth associated with the use of PRP has been reported. Previous studies showed using autologous leukocyte- and platelet-rich fibrin could increase vascularization during early healing of chronic rotator cuff tear, and that ultrasound-guided PRP injection is superior to dry needling in patients with supraspinatus tendon lesion. However, in a 1-yr randomized controlled trial with combination of 6 week physiotherapy program, PRP injection did not produce extra effect than placebo injection. Because controversy exists with regard to the effect of PRP injection, the investigators aim to investigate whether combination of PRP injection with physiotherapy program could produce superior effect than either treatment alone.

Official Title
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Platelet-rich Plasma Injections and Physiotherapy in the Treatment of Chronic Rotator Cuff Tendinopathy

Conditions
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PRP Injection Only, Physiotherapy Only, PRP and Physiotherapy

Intervention / Treatment
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* Other: PRP preparation
* Device: Physiotherapy
* Other: PRP and physiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic rotator cuff tendinopathy, including small (<1cm) rotator cuff tear (partial or full-thickness), proven by ultrasound. Duration of symptom longer than 1 month. Aged ≥20 years old. Exclusion Criteria: Fracture, dislocation, or arthritis of the shoulder, Previous shoulder joint surgery, Rotator cuff tear with size ≥ 1cm, Calcification of rotator cuff tendons, Severe medical comorbidities, e.g., malignant neoplasms, blood dyscrasia, and serious infection, etc., Pregnancy, Cognitive impairment (Mini-Mental Status Examination < 24), Hypersensitive to thrombin.

Ages Eligible for Study
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Minimum Age: 20 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PRP preparation<br>PRP will be prepared by taking 10ml venous blood which is then mixed with 2ml of thrombin and centrifuged in a specially designed tube at 3400 rotations per minute (rpm) for 15 minutes. Then about 2ml PRP will be extracted, and will be infiltrated to the lesion site under ultrasound guidance. The injection technique is similar to that described by Kesikburun .21 Patients in group 1 or group 3 will receive 2 injections of PRP, with 1 month interval. | Other: PRP preparation<br> <br> |
| Active Comparator: Physiotherapy<br>Physiotherapy includes hot pack, electric therapy and therapeutic exercise, which will be supervised by a senior physical therapist. The therapeutic exercise consists of active and passive stretch, and strengthening exercise of the rotator cuff, the shoulder girdle, and the pectoral muscles, 3 times a week, and will continue for 1.5 months. After 1.5 months' supervised training, home program exercise follows and will be continued for another 1.5 months. | Device: Physiotherapy<br> <br> |
| Active Comparator: PRP and physiotherapy<br>PRP will be prepared by taking 10ml venous blood which is then mixed with 2ml of thrombin and centrifuged in a specially designed tube at 3400 rotations per minute (rpm) for 15 minutes. Then about 2ml PRP will be extracted, and will be infiltrated to the lesion site under ultrasound guidance. The injection technique is similar to that described by Kesikburun .21 Patients in group 1 or group 3 will receive 2 injections of PRP, with 1 month interval;Physiotherapy includes hot pack, electric therapy and therapeutic exercise, which will be supervised by a senior physical therapist. The therapeutic exercise consists of active and passive stretch, and strengthening exercise of the rotator cuff, the shoulder girdle, and the pectoral muscles, 3 times a week, and will continue for 1.5 months. After 1.5 months' supervised training, home program exercise follows and will be continued for another 1.5 months. | Other: PRP and physiotherapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the VAS for pain | The VAS pain scores during Neer test will be obtained using a horizontal lines of 100 mm, with 0 on the left indicating no pain and 100 on the right indicating very severe pain. A VAS has been shown to be reliable and sensitive for quantifying pain, with test-retest reliability of >0.90.28 In previous studies of patients treated for various shoulder disorders, the responsiveness of VAS for pain was moderate to good. | Clinical evaluation will be conducted at pre-treatment, post-treatment 1.5 months and post-treatment 3 months and post-treatment 6 months after treatments. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the active ROM | The maximal active ROMs of the affected shoulder will be measured using a goniometer under the guidelines of the American Academy of Orthopedic Surgeons. These measurements included abduction in the frontal plane, forward flexion, internal rotation, and external rotation with the arm at 0 degrees of abduction. | Clinical evaluation will be conducted at pre-treatment, post-treatment 1.5 months and post-treatment 3 months and post-treatment 6 months after treatments. | 
| SPADI | The SPADI is a self-administered questionnaire to assess the pain and disability associated with shoulder diseases. It consists of 13 items being divided into 2 subclasses, 5 items for pain and 8 items for disabilities. The total SPADI score, which ranges between 0 and 100, is calculated by averaging the scores from the pain and disabilities subclasses. | Clinical evaluation will be conducted at pre-treatment, post-treatment 1.5 months and post-treatment 3 months and post-treatment 6 months after treatments. | 
| SF-36 | The SF-36 is a 36-item questionnaire that evaluates the quality of life . It is composed of eight subscales: physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health. Each subscale has a score range of 0-100, with a higher score indicating better health status. | Clinical evaluation will be conducted at pre-treatment, post-treatment 1.5 months and post-treatment 3 months and post-treatment 6 months after treatments. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rotator cuff tendinopathy, rotator cuff tear, platelet-rich plasma, physiotherapy, exercise