The Effect of Amniotic Membrane Injection as An Addition to Physical Therapy in Patients With Rotator Cuff Tear

Rotator cuff tear (RCT) is a commonly seen pathology in shoulder disease, which causes significant disability in daily living and work. Based on a cohort study of a large population, the prevalence of rotator cuff full-thickness tear was 20.7%. More broadly, the prevalence of rotator cuff abnormalities increased with age and up to 62% in population more than 80 years old. The pathophysiology of RCT could be attributed to extrinsic factors such as impingement by surrounding tissue and intrinsic factor such as tendon degeneration. According to previous study using histochemical and immunocytochemical techniques, fibrocartilaginous metaplasia, decreasing vascularity and fibroblast numbers were found in rotator cuff tear. Besides, the inflammatory response diminished as the tear size increased.

The treatment of RCT includes surgery and non-operative treatment. The prognosis depends on the symptoms, tear size, chronicity and other structures involvement. Previous meta-analysis study reported that the effectiveness between surgery and conservative treatment is similar in treating RCT. Therefore, relative rest, oral medication, physical therapy and injection therapy were commonly used in first-line treatments. When treating shoulder pain with injection therapy, steroid was often used at first for short-term pain relief and anti-inflammation. However, the potential cytotoxic effect was found and could be harmful in tendon repair. To accelerative the healing process of soft tissue injury, regenerative injection become more popular and expectable over past few years. A meta-analysis study reported the positive long-term effect of prolotherapy and platelet-rich plasma (PRP). More recently, bone marrow concentrate (BMC) and amniotic membrane (AM) have been used in soft tissue repair and many clinical studies are processing.

Study Overview

• Status: Completed
• Conditions: Rotator Cuff Tear; Ultrasonography; Rotator Cuff Tendinopathy
• Intervention / Treatment: Other: Physiotherapy (PT group); Other: Amniotic membrane preparation and injection (AM group)

Detailed Description

Rotator cuff tear (RCT) is a commonly seen pathology in shoulder disease, which causes significant disability in daily living and work. Based on a cohort study of a large population, the prevalence of rotator cuff full-thickness tear was 20.7%. More broadly, the prevalence of rotator cuff abnormalities increased with age and up to 62% in population more than 80 years old. The pathophysiology of RCT could be attributed to extrinsic factors such as impingement by surrounding tissue and intrinsic factor such as tendon degeneration. According to previous study using histochemical and immunocytochemical techniques, fibrocartilaginous metaplasia, decreasing vascularity and fibroblast numbers were found in rotator cuff tear. Besides, the inflammatory response diminished as the tear size increased.

The treatment of RCT includes surgery and non-operative treatment. The prognosis depends on the symptoms, tear size, chronicity and other structures involvement. Previous meta-analysis study reported that the effectiveness between surgery and conservative treatment is similar in treating RCT. Therefore, relative rest, oral medication, physical therapy and injection therapy were commonly used in first-line treatments. When treating shoulder pain with injection therapy, steroid was often used at first for short-term pain relief and anti-inflammation. However, the potential cytotoxic effect was found and could be harmful in tendon repair. To accelerative the healing process of soft tissue injury, regenerative injection become more popular and expectable over past few years. A meta-analysis study reported the positive long-term effect of prolotherapy and platelet-rich plasma (PRP). More recently, bone marrow concentrate (BMC) and amniotic membrane (AM) have been used in soft tissue repair and many clinical studies are processing.

In recent decades, PRP was widely used in soft tissue regeneration. Though many studies had discussed the effect of PRP injections on pain and shoulder function in RCT, the effectiveness remains controversial. Some newer scaffolds including bovine collagen and amnio-derived membranes were also applied to the RCT in recent years. The AM was separated from a donor's placenta, and is a non-immunogenic structure. In previous animal study, amniotic epithelial cells could produce transforming growth factor-β (TGF-β), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), transforming growth factor-α (TGF-α), keratinocyte growth factor and hepatocyte growth factor. AM was found having anti-inflammatory, antimicrobial, antiviral effect, regulatory effect on angiogenesis and anti-scarring effcts. AM was revealed a pluripotent tissue which makes it potential in regenerative medicine. In some case series research, positive results was reported in pain and shoulder function in rotator cuff tears.

To the best of our knowledge, there has been limited evidence of regenerative injection by AM in treating patients with rotator cuff tear. The aim of this study is to evaluate the effect of single injection of AM in addition to physical therapy on pain and shoulder function.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Shin Kong Wu Ho-Su Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. . symptomatic rotator cuff tendinopathy, including partial-thickness tear or small (<1cm) full-thickness tear, proven by ultrasound
2. . duration of symptom longer than 1 month
3. . age ≥20 years old

Exclusion Criteria:

1. .fracture, dislocation, or arthritis of the shoulder
2. . previous shoulder joint surgery
3. . rotator cuff full-thickness tear with size ≥ 1cm
4. . calcification of rotator cuff tendons
5. . severe medical comorbidities, e.g., malignant neoplasms, blood dyscrasia, and serious infection, etc.
6. . pregnancy
7. . cognitive impairment (Mini-Mental Status Examination < 24).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Amniotic membrane preparation and injection (AM group); The dehydrated AM product used in this study is derived from donated human placental tissue following healthy, live, caesarian section, full-term births which are then cleaned of blood under aseptic conditions. The product comes as a 20mg dry powder in a small vial stored at room temperature and mixed with 2 mL 0.9% sterile normal saline. Then the suspended AM will be injected to the injured tendon and the surrounding area with ultrasound-guidance via a 7cm, 23-gauge needle.	Other: Physiotherapy (PT group); 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 stretching, and strengthening exercise of the rotator cuff, the shoulder girdle, and the pectoral muscles, and scapular stabilization exercise, 3 times a week, and will be continued for 12 weeks.
Active Comparator: Physiotherapy (PT group ); 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 stretching, and strengthening exercise of the rotator cuff, the shoulder girdle, and the pectoral muscles, and scapular stabilization exercise, 3 times a week, and will be continued for 12 weeks.	Other: Amniotic membrane preparation and injection (AM group); The dehydrated AM product used in this study is derived from donated human placental tissue following healthy, live, caesarian section, full-term births which are then cleaned of blood under aseptic conditions. The product comes as a 20mg dry powder in a small vial stored at room temperature and mixed with 2 mL 0.9% sterile normal saline. Then the suspended AM will be injected to the injured tendon and the surrounding area with ultrasound-guidance via a 7cm, 23-gauge needle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Visual Analogue Scale (VAS)	The pain VAS during Neer test will be obtained using a horizontal line of 100 mm, with 0 on the left indicating no pain and 100 on the right indicating very severe pain. A pain VAS has been shown to be reliable and sensitive for quantifying pain, with test-retest reliability of >0.90.24 In previous studies of patients treated for various shoulder disorders, the responsiveness of VAS for pain was moderate to good.	change between baseline and at 4 weeks, 12 weeks, and 24 weeks after the beginning of the treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Shoulder Pain and Disability Index (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. Good validity and reliability had been proved in previous studies.	change between baseline and at 4 weeks, 12 weeks, and 24 weeks after the beginning of the treatment.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES)	The ASES is a composite instrument, requiring both a physician assessment and a patient-completed portion; however, it is commonly presented as solely the patient-reported survey. This includes a section on pain (7 items) and a section on activities of daily living (10 items). Scores range from 0 to 100 with a higher score indicating a better shoulder condition. The minimal detectable change was 9.7 points, and the minimal clinically important difference was 6.4 points.	change between baseline and at 4 weeks, 12 weeks, and 24 weeks after the beginning of the treatment.
Range of motion.	The passive ROMs of the affected shoulder will be measured using a goniometer with the guidelines of the American Academy of Orthopedic Surgeons.22 This measurement includes abduction in the frontal plane, forward flexion, internal rotation, and external rotation with the arm at 0 degrees of abduction. These ROM measurements of the shoulder using goniometer have been reported to have high inter-trial reliability when they are performed by the same physical therapist.	change between baseline and at 12 weeks, and 24 weeks after the beginning of the treatment.
Ultrasound image of the rotator cuff of the affected shoulder	EPIQ 5 (Phillips, USA) machine with a 18- to 4-MHz linear array transducer will be used for ultrasonographic examinations of the shoulder. The examination will be performed with the subjects in seated position and will be started from the biceps tendon, subscapularis tendon, supraspinatus tendon, infraspinatus tendon, and subacromial-subdeltoid bursa in both the transverse and longitudinal planes. AC joint will also be examined in the longitudinal plane.	change between baseline and at 4 weeks, 12 weeks, and 24 weeks after the beginning of the treatment.
Self-assessment of the treatment effect.	Patient's evaluation of the treatment effect consists of the answer to one question: "Is the treatment effective?" scored on a Likert scale (very effective=5, effective=4, not effective=3, worse=2, much worse=1).	change between baseline and at 4 weeks, 12 weeks, and 24 weeks after the beginning of the treatment.

Collaborators and Investigators

• Sponsor: Shin Kong Wu Ho-Su Memorial Hospital
• Investigators: Principal Investigator: Lin-Fen Hsieh, Shin Kong Wu Ho-Su Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2023
• Primary Completion (Actual): April 12, 2024
• Study Completion (Actual): April 12, 2024

Study Registration Dates

• First Submitted: February 8, 2022
• First Submitted That Met QC Criteria: April 1, 2022
• First Posted (Actual): April 11, 2022

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: ultrasonography; Rotator cuff tear; amniotic membrane; rotator cuff tendinopathy
• Additional Relevant MeSH Terms: Wounds and Injuries; Musculoskeletal Diseases; Muscular Diseases; Rupture; Shoulder Injuries; Tendon Injuries; Rotator Cuff Injuries; Tendinopathy
• Other Study ID Numbers: 20210711R

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No