Treatment of Intractable Common Extensor Tendon Injury Using Mesenchymal Stem Cells (Allo-ASC)

Study Overview
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Brief Summary
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The aim of this study is to evaluate the efficacy and safety of intra-tendon injection of allogeneic adipose-derived mesenchymal stem cells (Allo-ASC) in intractable common extensor tendinosis patients in comparison with a control treatment.

Detailed Description
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A phase II randomized placebo controlled trial will be done with following 3 groups. Each group will have 10 participants, so, the total patients will be 30 people. High concentration of Allo-ASC group: stem cell 0.5cc (Total: 10 million cells) + Fibrin glue 0.5cc Low concentration of Allo-ASC group: stem cell 0.5cc (Total: 1 million cells) + Fibrin glue 0.5cc Placebo Comparator (Fibrin) group: Normal saline 0.5cc + Fibrin glue 0.5cc The investigators will compare the efficacy difference with visual analogue scale (VAS) during activity (primary outcome), VAS at rest, Mayo elbow performance index (MEPI), grip strength, ultrasonographic assessment at baseline, 6 weeks, 12 weeks, 6 months, 12 months and 24 months after injection. Shear wave elastography (SWE) and magnetic resonance image (MRI) will be done at baseline, 12 weeks, 12 months and 24 months after injection

Official Title
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Treatment of Intractable Common Extensor Tendon Injury Using Allogeneic Adipose-derived Mesenchymal Stem Cells (Allo-ASC): a Phase II Randomized Controlled Trial

Conditions
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Lateral Epicondylitis

Intervention / Treatment
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* Biological: High concentration of Allo-ASC
* Biological: Low concentration of Allo-ASC
* Drug: Fibrin glue
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: clinically diagnosed as lateral epicondylosis (tennis elbow) symptom duration is over 12 months pain visual analogue scale (VAS) during activity ≥ 5 recurrent pain in spite of conservative treatment such as physical therapy, medication, steroid injection common extensor tendon injury can be observed under ultrasound (hypoechoic lesion) and MRI (hyperintensity or discontinuity) patient that can understand the clinical trials Exclusion Criteria: patient that underwent other injection such as steroid injection or prolotherapy within 6 weeks patients with following conditions (such as arthritis related to the target lesion, synovitis related to the target lesion, paralysis related to the target lesion, entrapment of related nerve to the target lesion, radiculopathy related to the target lesion, infectious disease, generalized pain syndrome, rheumatoid arthritis, impaired sensibility, dementia, history of allergic or hypersensitive reaction to bovine-derived proteins or Fibrin Glue, contraindication to MRI) patient that enrolled other clinical trials within 30 days current pregnancy or breast-feeding, planning for pregnancy history of drug/alcohol addiction, habitual smoker operation history of affected elbow previous clinical trial involving stem cell administration other severe medical illness or bleeding tendency size of intramural calcification over 2.0 mm under ultrasound evaluation

Ages Eligible for Study
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Minimum Age: 19 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: High concentration of Allo-ASC group<br>High concentration of Allo-ASC 0.5cc (Total: 10 million cells) & Fibrin glue 0.5cc by ultrasonographic guided intra-tendon injection | Biological: High concentration of Allo-ASC<br>* 10 million cells of Allo-ASC 0.5cc<br>Drug: Fibrin glue<br>* Fibrin glue 0.5cc<br>* Other names: Fibrin sealant;|
| Experimental: Low concentration of Allo-ASC group<br>Low concentration of Allo-ASC 0.5cc (Total: 1 million cells) & Fibrin glue 0.5cc by ultrasonographic guided intra-tendon injection | Biological: Low concentration of Allo-ASC<br>* 1 million cells of Allo-ASC 0.5cc<br>Drug: Fibrin glue<br>* Fibrin glue 0.5cc<br>* Other names: Fibrin sealant;|
| Placebo Comparator: Placebo Comparator (Fibrin) group<br>Normal saline 0.5cc & Fibrin glue 0.5cc by ultrasonographic guided intra-tendon injection | Drug: Fibrin glue<br>* Fibrin glue 0.5cc<br>* Other names: Fibrin sealant;Drug: Normal saline<br>* Normal saline 0.5cc<br>* Other names: 0.9% Sodium Chloride Solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of pain visual analogue scale (VAS) during activity | Self reported pain intensity during activity will be evaluated by visual analogue scale (0 = no pain, 10 = pain as bad as can be). | baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of pain visual analogue scale (VAS) during activity | Self reported pain intensity during activity will be evaluated by visual analogue scale (0 = no pain, 10 = pain as bad as can be). | baseline, 6 weeks, 12 weeks, 6 months, 12 months and 24 months | 
| Change of pain visual analogue scale (VAS) at rest | Self reported pain intensity at rest will be evaluated by visual analogue scale (0 = no pain, 10 = pain as bad as can be). | baseline, 6 weeks, 12 weeks, 6 months, 12 months and 24 months | 
| Change of Mayo elbow performance index (MEPI) | The MEPI measures pain, motion, stability, and daily functions. (0 = worst, 100 = best) | baseline, 6 weeks, 12 weeks, 6 months, 12 months and 24 months | 
| Ultrasonographic assessment | Ultrasonographic findings will be analyzed using a 5-point Likert scale (1: more aggravated, 2: aggravated, 3: same, 4: improved, 5: more improved). Sonographic images will be compared with baseline images by experienced ultrasound examiners being blind to the treatment group and the time points of image achievement. | baseline, 6 weeks, 12 weeks, 6 months, 12 months and 24 months | 
| Shear wave elastography | Young modulus and shear wave speed will be obtained | baseline, 12 weeks and 24 months | 
| Magnetic resonance image (MRI) assessment | MRI findings will be analyzed using a 5-point Likert scale (1: more aggravated, 2: aggravated, 3: same, 4: improved, 5: more improved). MR images will be compared with baseline images by experienced ultrasound examiners being blind to the treatment group and the time points of image achievement. | baseline, 12 weeks and 24 months | 

 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