Lateral Epicondylitis
Conditions
Keywords
adipose derived mesenchymal stem cell, allogeneic stem cell
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.
Interventions
BIOLOGICALALLO-ASC(allogeneic adipose derived mesenchymal stem cell) injection
Sponsors
Medical Research Collaborating Center, Seoul, Korea
Seoul National University Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Visual Analog Scale (VAS) at 6 and 12 Weeks | Baseline, 6 weeks, 12 weeks after intervention | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Modified Mayo Clinic Performance Index for the Elbow | Baseline, 6 weeks, 12 weeks after the intervention | The Modified Mayo clinic performance index for the elbow measures pain, motion, stability, and daily functions. (0 to 100) Higher score means better function. |
| Defect Area of Tendon by Ultrasonography in Long Axis | Baseline, 6 weeks, and 12 weeks after the intervention | 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. |
| Defect Area of Tendon by Ultrasonography in Short Axis | Baseline, 6 weeks, and 12 weeks after the intervention | 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. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1 Million Cells/ml of ALLO-ASC 1 million cells/ml of ALLO-ASC(allogeneic adipose derived mesenchymal stem cell) will be injected by ultrasound guided intervention.
ALLO-ASC(allogeneic adipose derived mesenchymal stem cell) injection | 6 |
| 10 Million Cells/ml of ALLO-ASC 10 million cells/ml of ALLO-ASC(allogeneic adipose derived mesenchymal stem cell) will be injected by ultrasound guided intervention.
ALLO-ASC(allogeneic adipose derived mesenchymal stem cell) injection | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | 10 Million Cells/ml of ALLO-ASC | 1 Million Cells/ml of ALLO-ASC | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 12 Participants |
| Age, Continuous | 50.5 years STANDARD_DEVIATION 11.1 | 53.2 years STANDARD_DEVIATION 8.3 | 51.7 years STANDARD_DEVIATION 9.5 |
| Region of Enrollment South Korea | 6 participants | 6 participants | 12 participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 3 / 6 | 3 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
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.
Time frame: Baseline, 6 weeks, 12 weeks after intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1 Million Cells/ml of ALLO-ASC | Change From Baseline in Visual Analog Scale (VAS) at 6 and 12 Weeks | Baseline | 3.57 score on a scale | Standard Deviation 2.1 |
| 1 Million Cells/ml of ALLO-ASC | Change From Baseline in Visual Analog Scale (VAS) at 6 and 12 Weeks | Post-injection 6 weeks | 2.93 score on a scale | Standard Deviation 3.06 |
| 1 Million Cells/ml of ALLO-ASC | Change From Baseline in Visual Analog Scale (VAS) at 6 and 12 Weeks | Post-injection 12 weeks | 1.68 score on a scale | Standard Deviation 1.9 |
| 10 Million Cells/ml of ALLO-ASC | Change From Baseline in Visual Analog Scale (VAS) at 6 and 12 Weeks | Baseline | 3.02 score on a scale | Standard Deviation 1.34 |
| 10 Million Cells/ml of ALLO-ASC | Change From Baseline in Visual Analog Scale (VAS) at 6 and 12 Weeks | Post-injection 6 weeks | 1.60 score on a scale | Standard Deviation 1.8 |
| 10 Million Cells/ml of ALLO-ASC | Change From Baseline in Visual Analog Scale (VAS) at 6 and 12 Weeks | Post-injection 12 weeks | 0.87 score on a scale | Standard Deviation 0.67 |
Comparison: Null hypothesis: There is no difference between the two groups at baselinep-value: 0.52Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis: There is no difference between the two groups at post-injection 6 weeks.p-value: 0.47Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis: There is no difference between the two groups at post-injection 12 weeks.p-value: 0.52Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: Baseline, 6 weeks, and 12 weeks after the intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1 Million Cells/ml of ALLO-ASC | Defect Area of Tendon by Ultrasonography in Long Axis | Baseline | 4197 mm^2 | Standard Deviation 2607 |
| 1 Million Cells/ml of ALLO-ASC | Defect Area of Tendon by Ultrasonography in Long Axis | Post-injection 6weeks | 4163 mm^2 | Standard Deviation 1751 |
| 1 Million Cells/ml of ALLO-ASC | Defect Area of Tendon by Ultrasonography in Long Axis | Post-injection 12 weeks | 2381 mm^2 | Standard Deviation 1342 |
| 10 Million Cells/ml of ALLO-ASC | Defect Area of Tendon by Ultrasonography in Long Axis | Baseline | 5246 mm^2 | Standard Deviation 2159 |
| 10 Million Cells/ml of ALLO-ASC | Defect Area of Tendon by Ultrasonography in Long Axis | Post-injection 6weeks | 4383 mm^2 | Standard Deviation 1558 |
| 10 Million Cells/ml of ALLO-ASC | Defect Area of Tendon by Ultrasonography in Long Axis | Post-injection 12 weeks | 2516 mm^2 | Standard Deviation 1989 |
Comparison: Null hypothesis: There is no difference between the two groups at baselinep-value: 0.262Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis: There is no difference between the two groups at post-injection 6 weeks.p-value: 0.631Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis: There is no difference between the two groups at post-injection 12 weeks.p-value: 0.796Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: Baseline, 6 weeks, and 12 weeks after the intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1 Million Cells/ml of ALLO-ASC | Defect Area of Tendon by Ultrasonography in Short Axis | Baseline | 3726 mm^2 | Standard Deviation 2341 |
| 1 Million Cells/ml of ALLO-ASC | Defect Area of Tendon by Ultrasonography in Short Axis | Post-injection 6 weeks | 3797 mm^2 | Standard Deviation 1753 |
| 1 Million Cells/ml of ALLO-ASC | Defect Area of Tendon by Ultrasonography in Short Axis | Post-injection 12 weeks | 2703 mm^2 | Standard Deviation 1418 |
| 10 Million Cells/ml of ALLO-ASC | Defect Area of Tendon by Ultrasonography in Short Axis | Baseline | 5018 mm^2 | Standard Deviation 2494 |
| 10 Million Cells/ml of ALLO-ASC | Defect Area of Tendon by Ultrasonography in Short Axis | Post-injection 6 weeks | 2849 mm^2 | Standard Deviation 1601 |
| 10 Million Cells/ml of ALLO-ASC | Defect Area of Tendon by Ultrasonography in Short Axis | Post-injection 12 weeks | 2223 mm^2 | Standard Deviation 599 |
Comparison: Null hypothesis: There is no difference between the two groups at baselinep-value: 0.337Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis: There is no difference between the two groups at post-injection 6 weeksp-value: 0.078Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis: There is no difference between the two groups at post-injection 12 weeks.p-value: 0.439Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: Baseline, 6 weeks, 12 weeks after the intervention
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| 1 Million Cells/ml of ALLO-ASC | Modified Mayo Clinic Performance Index for the Elbow | Baseline | 57.92 score on a scale | Standard Deviation 15.03 |
| 1 Million Cells/ml of ALLO-ASC | Modified Mayo Clinic Performance Index for the Elbow | Post-injection 6 weeks | 83.75 score on a scale | Standard Deviation 14.9 |
| 1 Million Cells/ml of ALLO-ASC | Modified Mayo Clinic Performance Index for the Elbow | Post-injection 12 weeks | 87.92 score on a scale | Standard Deviation 9.41 |
| 10 Million Cells/ml of ALLO-ASC | Modified Mayo Clinic Performance Index for the Elbow | Baseline | 70.00 score on a scale | Standard Deviation 9.22 |
| 10 Million Cells/ml of ALLO-ASC | Modified Mayo Clinic Performance Index for the Elbow | Post-injection 6 weeks | 90.41 score on a scale | Standard Deviation 6.97 |
| 10 Million Cells/ml of ALLO-ASC | Modified Mayo Clinic Performance Index for the Elbow | Post-injection 12 weeks | 91.67 score on a scale | Standard Deviation 1.44 |
Comparison: Null hypothesis: There is no difference between the two groups at baselinep-value: 0.227Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis: There is no difference between the two groups at post-injection 6 weeks.p-value: 0.573Wilcoxon (Mann-Whitney)
p-value: 0.588Wilcoxon (Mann-Whitney)