Mesenchymal Stem Cells and Amniotic Membrane Composite for Supraspinatus Tendon Repair Augmentation

The Efficacy of Using Allogeneic Adipose-derived Mesenchymal Stem Cells and Human Amniotic Membrane (AAdMSC-HAM) Composite for Supraspinatus Tendon Repair Augmentation

This is a non-randomized clinical trial conducted in a single tertiary hospital which investigates the efficacy of allogeneic adipose-derived mesenchymal stem cells and human amniotic membrane (AAdMSC-HAM) composite for supraspinatus tendon repair augmentation

Study Overview

• Status: Recruiting
• Conditions: Supraspinatus Tear
• Intervention / Treatment: Procedure: Tendon repair procedure; Procedure: Tendon repair augmented with AAdMSC-HAM composite

Detailed Description

Supraspinatus tendon tear is the most common factor causing shoulder pain, mainly resulting in discomfort and functional deficit in individuals over the age of 35. Supraspinatus tendon repair surgery represents one of the most widely performed types of orthopedic operation. Nevertheless, concerns persist regarding tendon-to-bone healing during the postoperative period. Despite advancements in surgical technique, re-tear of a previously repaired supraspinatus tendon is a fairly common complication, especially in a larger size tear. Such repair technique employing suture anchor devices alone has not yet produced functional results demonstrating both anatomical and biomechanical properties. Therefore, tendon tissue engineering using a combination of scaffolds, cells, and growth factors stimulation offers a potential solution as a biological augmentation in tendon repair.

Human amniotic membrane (HAM) has been widely used as a natural scaffold in tissue engineering due to many of its unique properties such as providing growth factors, cytokines and tissue inhibitors of metalloproteinases, adequate mechanical strength, and biocompatibility. Whereas, mesenchymal stem cells (MSCs) constitute one of the adult stem cells that promote replacement and repair of damaged tissue along with normal tissue turnover. These MSCs are seeded to the HAM scaffolds to biologically augment tendon repair, with MSCs acting as cytokines/growth factors to stimulate tissue repair. This approach serves as the foundation to conduct the present study. The investigators aim to investigate the efficacy of using allogeneic adipose-derived MSCs and human amniotic membrane (AAdMSC-HAM) composite for supraspinatus tendon repair augmentation.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Heri Suroto, MD, PhD; Phone Number: 62 31 5038335; Email: hsuroto2000@yahoo.com
• Study Contact Backup: Name: Heri Suroto, MD, PhD; Phone Number: 62 31 5020251; Email: heri-suroto@fk.unair.ac.id

Study Locations

• Indonesia
  • East Java
    • Surabaya, East Java, Indonesia, 60286
      • Recruiting
      • Dr. Soetomo General Academic Hospital/ Department Orthopaedic & Traumatology Faculty of Medicine Universitas Airlangga
      • Contact: Heri Suroto, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 31 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Suffering from complete/total tear of supraspinatus tendon for a duration of fewer than 12 months
• Diagnosis is established based on clinical condition and ultrasonography or MRI examination

Exclusion Criteria:

• Patients with comorbid diseases: Diabetes Mellitus, Rheumatoid Arthritis, and other inflammatory diseases.
• Patients presenting with other related injuries, such as fractures or dislocation around the shoulder joint.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group (Tendon repair); The control group will undergo tendon repair procedure only (without augmentation)	Procedure: Tendon repair procedure; Tendon repair procedure: Single senior surgeon (HS) will perform mini-open surgery to decompress the acromioplasty and repair the supraspinatus tendon.; Splicing is achieved by installing screw-type anchors on the insertional footprint of the humeral head greater tuberosity.; Then, double suturing of the supraspinatus tendon is performed.
Experimental: Experimental group (Tendon repair augmented with AAdMSC-HAM composite); The experimental group will undergo tendon repair procedure augmented with AAdMSC-HAM composite	Procedure: Tendon repair augmented with AAdMSC-HAM composite; After double suturing of the supraspinatus tendon, the composite comprising freeze-dried HAM (2 cm x 2 cm x 0.002 cm) and AAdMSC (20 million cells) is placed on the upper surface of the splice and fixed with stitches at all four corners.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Active range of motion (AROM) pre-surgery	Shoulder: flexion, extension, abduction, adduction, external rotation, internal rotation. The tests are performed by two blinded assessor, and expressed in degrees.	Pre-surgery
Active range of motion (AROM) at 12 months follow-up	Shoulder: flexion, extension, abduction, adduction, external rotation, internal rotation. The tests are performed by two blinded assessor, and expressed in degrees.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain pre-surgery	Measured by visual analogue scales (VAS). Patients are asked to described their level of pain from the scale 0 to 10 (0 indicating no pain, 1-3 indicating mild pain, 4-6 indicating moderate pain, 7-9 indicating severe pain, and 10 indicating the worst, unbearable pain). The lower scores mean a better pain outcome	Pre-surgery Outcome
Pain at follow-up 12 months	Measured by visual analogue scales (VAS). Patients are asked to described their level of pain from the scale 0 to 10 (0 indicating no pain, 1-3 indicating mild pain, 4-6 indicating moderate pain, 7-9 indicating severe pain, and 10 indicating the worst, unbearable pain). The lower scores mean a better pain outcome	12 months
Disabilities of the Arm, Shoulder, and Hand (DASH) score pre-surgery	DASH score is a self-assessment of symptoms and function of the entire upper extremity comprising 30 items. Each item consists of five levels of answers (1=no difficulty/symptoms, 2=mild difficulty/symptoms, 3=moderate difficulty/symptoms, 4=severe difficulty/symptoms, and 5=extreme difficulty (unable to do)/symptoms). The scores are then used to calculate a scale score ranging from 0 (no disability) to 100 (most severe disability). Greater DASH scores reflect greater disability (worse outcome).	Pre-surgery
Disabilities of the Arm, Shoulder, and Hand (DASH) score at follow-up 12 months	DASH score is a self-assessment of symptoms and function of the entire upper extremity comprising 30 items. Each item consists of five levels of answers (1=no difficulty/symptoms, 2=mild difficulty/symptoms, 3=moderate difficulty/symptoms, 4=severe difficulty/symptoms, and 5=extreme difficulty (unable to do)/symptoms). The scores are then used to calculate a scale score ranging from 0 (no disability) to 100 (most severe disability). Greater DASH scores reflect greater disability (worse outcome).	12 months
Constant-Murley Score (CS) pre-surgery	The scoring system records individual parameters and provides an overall clinical functional assessment. It consists of 4 domains: pain, activities of daily living (ADL), mobility, and power/strength. Pain and ADL are self-assessed, while all other items are assessed by the blinded examiner. A higher score shows a better function (100 as the best), while a lower score shows a worse function (0 as the worst).	Pre-surgery
Constant-Murley Score (CS) at follow-up 12 months	The scoring system records individual parameters and provides an overall clinical functional assessment. It consists of 4 domains: pain, activities of daily living (ADL), mobility, and power/strength. Pain and ADL are self-assessed, while all other items are assessed by the blinded examiner. A higher score shows a better function (100 as the best), while a lower score shows a worse function (0 as the worst).	12 months
Tear recurrence (re-tear)	A systematic review (D'Ambrosi et al., 2019) showed that re-tear rates after rotator cuff repair with scaffolds were 17.97%. We hypothesize that the augmentation using HAM (as scaffold) seeded with AAdMSC would further lower the re-tear rates. We plan to record the recurrence of supraspinatus tendon tear (if any) based on radiographic evaluation with ultrasonography, which will then be confirmed with MRI. Ultrasonography provides an excellent anatomical evaluation of soft tissue which is able to assess any alterations during active locomotion. However, due to its user-dependent nature, we will also confirm the findings with MRI examination. Any grade of re-tear (grade I-III as evaluated by ultrasonography and confirmed with MRI) will be counted in and classified as "re-tear". When the patients do not complain about any symptoms of re-tear, we will record them as "no re-tear".	Throughout the study duration (12 months), recorded as the first time complained by the patients (i.e. after "n" months).

Collaborators and Investigators

• Sponsor: Dr. Soetomo General Hospital
• Investigators: Principal Investigator: Heri Suroto, MD, PhD, Cell and Tissue Bank-Regenerative Medicine, Dr. Soetomo General Academic Hospital, Indonesia

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2019
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: December 8, 2020
• First Submitted That Met QC Criteria: December 15, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Actual): December 17, 2020
• Last Update Submitted That Met QC Criteria: December 15, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Mesenchymal stem cells; Amniotic membrane; Supraspinatus tear; Supraspinatus rupture; Tendon repair; Tendon tissue engineering
• Other Study ID Numbers: 1208/KEPK/V/2019

Drug and device information, study documents

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