The Effects of Platelet-Rich Plasma Versus Prolotherapy On Rotator Cuff Tendinopathy: A Randomized Controlled Trial.

Study design This study is a randomized, double-blind, controlled trial conducted at the University of Malaya Medical Centre, Kuala Lumpur, Malaysia.

Patients The patients will be recruited from the following clinics: Sports Medicine, orthopaedic, rheumatology, outpatient and staff health. Notice of study invitation in this study will be distributed to all the respective clinic. Patients with a confirm diagnosis of supraspinatus tendinopathy by ultrasound or MRI will be invited to participate in this study. Study screening will be carried out to ensure the inclusion and exclusion criteria are fulfilled by the research team in Sports Medicine Clinic.

Procedures

PRP group Patients under PRP group will receive a single 2 mL injection of PRP into the injury site under ultrasound guidance administered by a sports physician. The PRP will be prepared using a commercial kit, Y-Cell BioKit Systems.

Prolotherapy group Patients in the prolotherapy group will receive a single 2 mL injection of 16.5% dextrose solution administered under ultrasound guidance.

Injection technique Injection will be performed in the Sports Medicine Clinic using aseptic technique. Both the PRP and prolotherapy will be prepared in a syringe and covered with a black tape to ensure the patients did not know the content of the syringe. Patients will be placed in the supine position and will be requested not to turn their head during the procedure. A 22 G needle will be used for injection under ultrasound guided.

Following injection, cryotherapy will be applied for 15 min. Upon discharge, patients will be advised to rest the injected shoulder for the next 48 hours and to avoid taking NSAIDs.

Rehabilitation program Patients will receive a booklet for shoulder stretching and strengthening exercise. A logbook will be provided for the patients to record their exercise session. Rehabilitation sessions will be advise to commenced only day three of injection.

Sample size The sample size was estimated based on the primary outcome of functional score. Improvement was defined by a decrease in the mean Shoulder Pain and Disability Index (SPADI) of 17.7 ± 3.7 in the platelet-rich plasma group11 and 16.12 ± 12.8211 for prolotherapy. For this study, the sample size was calculated after taking into account the desired statistical significance level set at 5%, and the power of the study set at 80%, with type I error rate of less than 0.05 is permitted and a false-negative rate of less than 0.20. The sample size is calculated using the G*Power version 3.1.9.2 software11. With the assumption of 30% drop out, hence, to detect a difference in the functional outcome, a minimum of 30 patients in each group is required.

Randomization Randomization will be performed using computer-generated block randomization of ten. Subjects will be randomized into either PRP group or Prolo group.

Blinding The patients and assessors will be blind to the intervention. Two sports physician who not directly involved in the randomization and injection will perform the outcome measure assessment.

Outcomes

Patients characteristics Patients sociodemographic information, including gender, date of birth, ethnic background, job description and recreational activities will be recorded. Information related to the shoulder pain such as duration and other past rehabilitation and treatment will also be documented.

Primary outcome measures The primary outcome of this study is pain score using the visual analog score (VAS) score and shoulder function using shoulder pain and disability index (SPADI) score.

VAS score (7) is a continuous scale, 10 cm length with the left most anchor indicate "no pain" (0) to "extreme pain" (10).

SPADI was used to measure shoulder pain and disability in an outpatient setting within the recent 1 week. It contains 13 items that assess pain and disability. SPADI reveals good construct validity, correlating well with other specific shoulder questionnaires and responsive to change over time (8).

Secondary outcome measures

1. Constant-Murley score assessed four aspects of shoulder injury which consist of two subjective item- pain and activities of daily living (ADL) and two objective item- range of motion (ROM) and strength. This score was used in many shoulder studies and had good response to change quality (9).
2. Clinical test which consist of special test
3. Biomedical test which consist of shoulder ROM using goniometer, strength using dynamometer and periscapular muscle activities using electromyogram.
4. Adverse effect of the injections will also be recorded.

Data collection and management Data will be collected from patients at baseline, 3 weeks, 6 weeks, 3 months and 6 months. All data collected will be stored securely in a locked cabinet in Sports Medicine Department throughout the trial and only can be access by the researcher involved. To ensure confidentiality, each patient will have the trial identification number.

Statistical analysis The outcome variables will be analyzed with the principle of intention-to-treat (ITT). The mean VAS score and SPADI between groups will be compared using either the parametric independent t-test or non-parametric test using Mann-Whitney U test. The secondary outcome measures will be examine using linear mixed- model analysis. All statistical analysis will be performed using the SPSS V.25.0 (SPSS), and a p value of \<0.05 will be considered to be significant.

Ethics and dissemination The study was approved by the Medical Research Ethics Committee of the University of Malaya Medical Centre (MREC ID: 201977-7623). This trial was registered at the National Medical Research Register (NMRR-19-1658-48279). Participation in this study is strictly voluntary. Possible patients will be informed of all the procedures involved in the reserach verbally and by the patient's information sheets. Patients will be required to sign the informed consent form before participation. Patient will be allowed to withdraw from the study at any time. Results from this study will be presented at scientific conferences and publish in journal.