Treatment of Tendon Injury Using Allogenic Adipose-derived Mesenchymal Stem Cells (Rotator Cuff Tear)

Study Overview
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Brief Summary
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Main purpose of this study is to evaluate efficacy of allogenic adipose-derived mesenchymal stem cells in treatment of tendon injury. ALLO-ASC will be administrated to the patients with supraspinatus partial thickness tear by ultrasonographic guided injection.

Detailed Description
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Injection volume depends on the size of lesion on ultrasound examination. And all injection will be done under ultrasound guidance. Double blind Randomized placebo controlled study will be done with following 3 groups. Each group will have 8 people, so, the total patients will be 24 people. Stem cell treatment group : stem cell 0.5cc (Total: 10 million cells) + Fibrin glue 0.5cc + range of motion exercise Active control (fibrin glue) group : Normal saline 0.5cc + Fibrin glue 0.5cc + range of motion exercise Control (normal saline) group : Normal saline 0.5cc + Normal saline 0.5cc + range of motion exercise The investigators will compare the efficacy difference with VAS(visual analog scale, primary outcome), ASES(American Shoulder and Elbow Surgeons) Score, UCLA(University of California, Los Angles) Shoulder Score, DASH(The Disabilities of the Arm, Shoulder and Hand) Score and change of tear size compared to the baseline image assessed by MRI. These measurement will be done at 6 and 12 weeks after injections and long-term follow-up will be also planned to 6 months, 12months and 24 months except for the evaluation of the tear size which will be done at baseline, 3 months and 24 months after the intervention.

Official Title
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Treatment of Tendon Injury Using Allogenic Adipose-derived Mesenchymal Stem Cells: Phase II Double-Blind Placebo-Controlled Randomized Clinical Trials.

Conditions
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Rotator Cuff Tear

Intervention / Treatment
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* Biological: allogenic adipose stem cell injection
* Biological: fibrin glue/normal saline injection
* Biological: normal saline injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: clinically diagnosed as rotator cuff tear (supraspinatus partial thickness tear) recurrent pain in spite of conservative treatment such as physical therapy, medication, steroid injection symptom duration is over 3 months supraspinatus partial thickness tear proven ultrasonography and magnetic resonance image(MRI) patient that can understand the clinical trials Exclusion Criteria: patient that underwent other injection treatment within 6 weeks some associated diseases (adhesive capsulitis, full thickness supraspinatus tear,. arthritis of related joint to the target lesion, muscle weakness or atrophy, innervated by suprascapular nerve, paralysis of related joint to target lesion, proximal humeral fracture, infectious disease, bilateral rotator cuff tear, generalized pain syndrome, radiculopathy, rheumatoid arthritis, impaired sensibility, dementia, history of allergic or hypersensitive reaction to bovine-derived proteins or fibrin glue and contraindication to MRI patient that enrolled other clinical trials within 30 days history of drug/alcohol addiction, habitual smoker, operation, allergic reaction to fibrin glue, local anesthetics and bovine-derived proteins and severe medical disease.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 90 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesenchymal stem cell group<br>Received allogenic adipose tissue-derived adult mesenchymal stem cells (10million cells) in fibrin glue scaffold. | Biological: allogenic adipose stem cell injection<br>* Intervention will be done with stem cell injection, 0.5cc (Total: 10 million cells), fibrin glue injection 0.5cc and range of motion exercise.<br>* Other names: experimental group;|
| Active Comparator: Active control (fibrin glue) group<br>Received fibrin glue and normal saline. | Biological: fibrin glue/normal saline injection<br>* Total 1cc of fibin glue and normal saline mixture injection and range of motion exercise<br>* Other names: active control group;|
| Placebo Comparator: Control (normal saline )group<br>Received only normal saline. | Biological: normal saline injection<br>* Total 1cc of normal saline injection and range of motion exercise<br>* Other names: placebo group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Pain During Activity From Baseline to 3 Months After Intervention | Pain during activity will be evaluated by visual analog scale (active pain VAS). The active pain visual analog scale change from baseline to 3 months after intervention is the primary outcome. Visual analog scale is scored 0 to 10, higher scored meaning worse outcome. Negative values in change of pain during activity indicate improvement in pain. | Baseline and 3 months after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain During Rest | Pain during rest assessed by visual analog scale (VAS), scored 0 to 10, higher scores meaning worse outcome. | Baseline, 6 weeks, 12 weeks, 6, 12, 24 months after intervention | 
| Pain During Activity | Pain during activity assessed by visual analog scale (VAS), scored 0 to 10, higher scores meaning worse outcome | Baseline, 6 weeks, 12 weeks, 6, 12, 24 months after intervention | 
| American Shoulder and Elbow Surgeons (ASES) Shoulder Score | Functional score of the shoulder was assessed by American Shoulder and Elbow Surgeons shoulder score which is a questionnaire dedicated to the functional evaluation of the shoulder. It is scored from 0 to 100, higher scores meaning better outcome. | Baseline, 6 weeks, 12 weeks, 6, 12, 24 months after intervention | 
| Disability of Arm, Shoulder and Hand (DASH) Score | Shoulder function is assessed by DASH score which is questionnaire dedicated to evaluate the function of the upper extremity. It is scored from 0 (no disability) to 100 (most severe disability). | Baseline, 6 weeks, 12 weeks, 6, 12, 24 months after intervention | 
| University of California, Los Angeles(UCLA) Shoulder Score | Shoulder function is assessed by UCLA shoulder score which is a composite of range of motion examination and questionnaire dedicated to evaluate the function of the shoulder. It is scored from 0 to 35, higher scores meaning better shoulder function. | Baseline, 6 weeks, 12 weeks, 6, 12, 24 months after intervention | 
| Tear Size at 3 Months After Injection | Tear size was evaluated by 3-point Likert scale using MRI. The 3months follow-up images were compared to the baseline image and graded either; improved, stationary, and aggravated. | baseline and 3 months after intervention | 
| Tear Size at 12 Months After Injection | Tear size was evaluated by 3-point Likert scale using MRI. The 12 months follow-up images were compared to the baseline image and graded either; improved, stationary, and aggravated. | baseline and12 months after intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adipose derived mesenchymal stem cell, allogeneic stem cell, Rotator cuff tear