Treatment of Tendon Injury Using Mesenchymal Stem Cells

Study Overview
=================
Brief Summary
-----------------
Main purpose of this study is to evaluate efficacy and safety of allogenic adipose-derived mesenchymal stem cells(ALLO-ASC) in treatment of tendon injury. ALLO-ASC will be administrated to the patients with lateral epicondylitis by ultrasonographic guided injection.

Detailed Description
-----------------
Injection volume depends on the size of lesion on ultrasound examination. And all injection will be done under ultrasound guidance. First the investigators will administrate 1 million cells/ml (Group 1 for 6 participants). After monitoring the safety of injection for 2 weeks (the investigators will use WHO recommendations for grading of acute and subacute toxic effects), the investigators decide to increase the quantity as 10 million cells/ml (Group 2 for participants). The investigators will compare the efficacy difference as quantity increase. For efficacy measurement, VAS/modified Mayo clinic performance index for elbow/lesion measurement by ultrasound will be used at 6 and 12 weeks after injections.

Official Title
-----------------
Treatment of Tendon Injury Using Allogenic Adipose-derived Mesenchymal Stem Cells(ALLO-ASC):A Pilot Study

Conditions
-----------------
Lateral Epicondylitis

Intervention / Treatment
-----------------
* Biological: ALLO-ASC(allogeneic adipose derived mesenchymal stem cell) injection


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: clinically diagnosed as lateral epicondylitis (tennis elbow) recurrent pain in spite of conservative treatment such as physical therapy, medication, steroid injection symptom duration is over 6 months defect in common extensor tendon can be observed under ultrasound patient that can understand the clinical trials Exclusion Criteria: patient that underwent other injection treatment within 6 weeks some associated diseases (such as arthritis, synovitis, entrapment of related nerve, radiculopathy to the target lesion, generalized pain syndrome, rheumatoid arthritis, pregnancy, impaired sensibility, paralysis, history of allergic or hypersensitive reaction to bovine-derived proteins or fibrin glue) patient that enrolled other clinical trials within 30 days history of drug/alcohol addiction, habitual smoker

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 million cells/ml of ALLO-ASC<br>1 million cells/ml of ALLO-ASC(allogeneic adipose derived mesenchymal stem cell) will be injected by ultrasound guided intervention. | Biological: ALLO-ASC(allogeneic adipose derived mesenchymal stem cell) injection<br> <br> |
| Active Comparator: 10 million cells/ml of ALLO-ASC<br>10 million cells/ml of ALLO-ASC(allogeneic adipose derived mesenchymal stem cell) will be injected by ultrasound guided intervention. | Biological: ALLO-ASC(allogeneic adipose derived mesenchymal stem cell) injection<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Visual Analog Scale (VAS) at 6 and 12 Weeks | Self reported pain intensity during activity will be evaluated by visual analogue scale (0 = no pain, 10 = pain as bad as can be), higher scores meaning worse outcome. | Baseline, 6 weeks, 12 weeks after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Mayo Clinic Performance Index for the Elbow | The Modified Mayo clinic performance index for the elbow measures pain, motion, stability, and daily functions. (0 to 100) Higher score means better function. | Baseline, 6 weeks, 12 weeks after the intervention | 
| Defect Area of Tendon by Ultrasonography in Long Axis | Defect areas were measured as the largest defect of the common extensor tendon. Higher value means larger defect area. With the patient supine position with the elbow in 30' flexion and full pronation, the cephalic end of the ultrasound transducer was placed on the lateral epicondyle and the long axis of the transducer was aligned with the long axis of radius. The alignment of the transducer and radius was achieved by visualizing contours of the bony structures. Multiple cross-sectional images were saved by shifting the transducer medio-laterally by 2mm at a time. Acquiring images were repeated three times. Among the saved images, one image showing the largest defect were selected for every patients at every time points. Manual measurements of the defect area were conducted by tracking the perimeter using ImageJ 1.48 software (National Institutes of Health, http://imagej.nih.gov/ij/) and were repeated three times by two examiners in random orders and then, averaged. | Baseline, 6 weeks, and 12 weeks after the intervention | 
| Defect Area of Tendon by Ultrasonography in Short Axis | Defect areas were measured as the largest defect of the common extensor tendon. Higher value means larger defect area. With the patient supine position with the elbow in 30' flexion and full pronation, the transducer was placed on the proximal forearm just distal to the radial head, aligning the long axis of the transducer perpendicular to the long axis of the forearm. Viewing the round radius at the horizontal center, the transducer was shifted proximally by 2mm and multiple images were saved after the transducer passed the radial head until it slid over the prominence. Acquiring images were repeated three times. Among the saved images, one image showing the largest defect were selected for every patients at every time points. Manual measurements of the defect area were conducted by tracking the perimeter using ImageJ 1.48 software (National Institutes of Health, http://imagej.nih.gov/ij/) and were repeated three times by two examiners in random orders and then, averaged. | Baseline, 6 weeks, and 12 weeks after the intervention | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
adipose derived mesenchymal stem cell, allogeneic stem cell