Prolotherapy Intervention in Patient With Frozen Shoulder

Study Overview
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Brief Summary
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Introduction : Prolotherapy is regenerative tissue therapy that is considered to be efficacious in reducing symptoms and morbidity of frozen shoulder, but only a few studies demonstrate the effect of prolotherapy at the biomolecular level, particularly the level of Matrix Metalloproteinase- I (MMP-1), Tissue Inhibitor Matrix Metalloproteinase (TIMP-1), as the biomarkers of cartilage repair. Objective: To determine the effect of prolotherapy on MMP-1, TIMP-1, and functional outcomes in frozen shoulder patients Method: a double-blind randomized controlled trial study involving participants who had been diagnosed with Frozen Shoulder. History taking, functional outcome assessment, MMP-1, and TIMP-1 were measured. The prolotherapy via intraarticular and extraarticular was performed four times, followed by the evaluation of functional outcome, MMP-1, and TIMP-1 at week 12 Alternative Hypothesis : Prolotherapy will increase the MMP-1, TIMP-1 levels, and improve functional outcome among Frozen Shoulder patients

Detailed Description
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Design : Double-blind randomized trial Randomization : Simple Randomization generated by an online randomizer Sample Size : Difference between two means of primary outcome where mean difference (μ 1 - μ 2 ) = 0.47 pool variance = 0.09 Z 1-α/2 = 1.95 with type 1 error 5% 1-β = 1.282 with power 90%. Yielding 16 patients for each arm Detailed Intervention Intervention group: Prolotherapy is given four times (Week 0, Week 2, Week 4, and Week 6) Comparison group: Normal Saline is given four times with a timeframe similar to the intervention group Injection location Rotator Cuff muscles Intraarticular glenohumeral joint Subacromial bursa long-heap of the biceps tendon Acromioclavicular joint Statistical analysis : Descriptive statistic to elaborate baseline characteristic Assuming the baseline characteristic between groups are similar, the independent t-test will be conducted to see the differences between group, whereas Mann Whitney will be performed for nonparametric data Difference within-group (baseline and last day) will be measured by paired-t-test or Wilcoxon for non parametric scenario

Official Title
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The Level of Matrix Metalloproteinase-1 (MMP-1), Tissue Inhibitor Matrix Metalloproteinase-1 (TIMP-1) After Prolotherapy Intervention and The Functional Outcome in Patient With Frozen Shoulder

Conditions
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Frozen Shoulder

Intervention / Treatment
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* Drug: Dextrose 15 % in Water
* Drug: Normal Saline 20 mL Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age 35-70 Diagnosed with frozen shoulder At least showing symptoms more than 3 months Exclusion Criteria Receiving other intraarticular injection Taking Nonsteroid Antiinflammation drugs 1 week prior to intervention Skin disorder around the injection site Septic arthritis

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 70 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
Interventional Model Description: This study involves two arms assigned randomly for receiving different treatments. One arm for Prolotherapy and Normal Saline in the comparison group.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prolotherapy<br>A solution of 7.5 ml of 15% dextrose with 2 ml of 40% lidocaine and 10.5 water is given to these shoulder segments as follows. Supraspinatus muscle 2-4 ml Infraspinatus muscle 2-4 ml Teres minor muscle 2-3 ml, Subscapularis muscle 2-3 ml. Intraarticular glenohumeral joint 5 ml Bursa sub acromial 1-2 ml, Long head tendon biceps 1-2 ml Acromioclavicular joint 1 ml | Drug: Dextrose 15 % in Water<br>* A 15% dextrose solution is given to shoulder segments four times with 2 weeks interval (week 0,2,4, and 6)<br>* Other names: Prolotherapy;|
| Placebo Comparator: Normal Saline 0.9%<br>A solution of 20 ml normal saline 0.9% is given to these shoulder segments as follows. Supraspinatus muscle 2-4 ml Infraspinatus muscle 2-4 ml Teres minor muscle 2-3 ml, Subscapularis muscle 2-3 ml. Intraarticular glenohumeral joint 5 ml Bursa sub acromial 1-2 ml, Long head tendon biceps 1-2 ml Acromioclavicular joint 1 ml | Drug: Normal Saline 20 mL Injection<br>* A Normal Saline 0.9% is given to shoulder segments four times with 2 weeks interval (week 0,2,4, and 6)<br>* Other names: Comparator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Matrix Metalloproteinase 1 in Blood | Matrix Metalloproteinase 1 from whole blood measured using Enzyme-linked Immunoassay (ELISA). Mean difference between group will be assessed | changes of Matrix Metalloproteinase 1 value from baseline to week 6 | 
| Tissue Inhibitor Metalloproteinase 1 in Blood | Tissue Inhibitor Metalloproteinase 1 from whole blood measured using Enzyme-linked Immunoassay (ELISA). Mean difference between group will be assessed | changes of Tissue Inhibitor Metalloproteinase 1 value from baseline to week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Functional Outcome of the Shoulder | The functional outcome is measured using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire where the patient were asked to do simple task involving the arm, shoulder and hand and also the assessment of additional symptoms and impact to daily life. Higher score indicates disabilities | changes of Functional Outcome value from baseline to week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MMP-1, TIMP-1, Prolotherapy, Functional Outcome, Frozen Shoulder