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

Supraspinatus Tear Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04670302
• Other study ID #: 1208/KEPK/V/2019
• Status: Recruiting
• Phase: N/A
• Start date: October 17, 2019
• Est. completion date: December 31, 2022

Study information

• Verified date: December 2020
• Source: Dr. Soetomo General Hospital
• Contact: Heri Suroto, MD, PhD
• Phone: 62 31 5038335
• Email: hsuroto2000[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 35 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Supraspinatus Tear

Intervention

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.
• 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.

Locations

Country	Name	City	State
Indonesia	Dr. Soetomo General Academic Hospital/ Department Orthopaedic & Traumatology Faculty of Medicine Universitas Airlangga	Surabaya	East Java

Sponsors (1)

Lead Sponsor	Collaborator
Dr. Soetomo General Hospital

Country where clinical trial is conducted

Indonesia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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).