Connective Tissue Matrix (CTM) for Rotator Cuff Tendinopathy

Study Overview
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Brief Summary
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The purpose of this research study is to determine if the effectiveness of a single injection of CTM Boost in the treatment of patients with rotator cuff tendinopathy (RCT) is as effective as a single injection of platelet rich plasma (PRP) in reducing the symptoms of RCT.

Detailed Description
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Rotator cuff tendinopathy (RCT), is a chronic degenerative process which causes both shoulder pain as well as limited range of motion. It is currently estimated that approximately 5% of RCT is being managed surgically, which highlights the importance of effective non-operative treatment strategies. The advent of platelet rich plasma (PRP), a sample of blood drawn from a patient and concentrated to include mainly platelets and potent inflammatory mediators which promote healing, has shown promise as another treatment modality when injected at the site of tendon damage. Placenta-derived decellularized connective tissue matrix (CTM) may represent an alternative therapy for RCT. Placenta-derived biologics can be administered as an injection and have been shown to promote tenocyte proliferation and to reduce inflammation in vitro, thus potentially accelerating and enhancing tendon healing. This study is being conducted to determine if injection of CTM Boost is non-inferior to injection of PRP with regard to pain and function at Month 6 post-injection in patients with rotator cuff tendinopathy.

Official Title
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Connective Tissue Matrix (CTM) for Rotator Cuff Tendinopathy: A Randomized Controlled Trial

Conditions
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Tendinopathy, Shoulder Pain, Rotator Cuff Tendinitis, Rotator Cuff Tendinosis

Intervention / Treatment
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* Biological: CTM Boost
* Biological: PRP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18-80 years old with rotator cuff tendinopathy A PRP or CTM-type injection was determined by the clinician to be the proper medical treatment course and patient is willing to undergo the injection Exclusion Criteria: Patients with adhesive capsulitis Patients with acromio-clavicular joint impingement, retracted tears, significant labral lesions or significant glenohumeral arthrosis Patients with joint instability History of shoulder surgery or corticosteroid injection in the past 3 months Patients with any medical conditions that affect healing, such as end-stage renal disease or uncontrolled diabetes

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Two-arm, double-blinded, randomized controlled trial with the primary objective of evaluating non-inferiority of CTM (study intervention arm) to PRP (active comparator arm) for rotator cuff tendinopathy pain and function.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CTM Treatment<br>2.0 cc (cubic centimeter) dose injection of CTM Boost will be administered by injection directly into the rotator cuff using a 20 gauge needle. | Biological: CTM Boost<br>* Connective Tissue Matrix (CTM) Boost is a decellularized Human Cellular and Tissue Based Allograft derived from placental connective tissue. It is considered a minimally-manipulated biologic by the FDA and is marketed as an allograft for repairing connective tissue. It is administered via injection.<br>|
| Active Comparator: PRP Treatment<br>Each participant randomized to this arm will receive a single injection of Platelet Rich Plasma (PRP). | Biological: PRP<br>* PRP is derived by a sample of blood drawn from a patient and concentrated to include mainly platelets and potent inflammatory mediators which promote healing. At baseline, a blood draw of 60 milliliter (mL) will be obtained and concentrated in an Angel System to yield 5 cc of PRP and a supra-physiological concentration of white blood cells. All injections will be done under ultrasound guidance. A two-part injection process will be used. An advancing 20 gauge 1.5-inch needle first placed 3 mL of 1% xylocaine proximal to the tendinopathic area or tear. The needle will then be re-inserted at the proximal aspect of the lesion and slowly removed while infiltrating of 5 mL of PRP without activation with Calcium Chloride/thrombin at the lesion and surrounding tendon.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| determine if injection of CTM Boost is non-inferior to injection of PRP | Mean Western Ontario Rotator Cuff Index (WORC) Score The WORC has 21 items in four domains, including physical symptoms (10 questions), sports/recreation/work (4 questions), lifestyle (4 questions) and emotions (3 questions). Raw scores range from 0 to 2100, with a higher score indicating decreased quality of life because of pathological condition of the rotator cuff. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| assessment of superiority of CTM to PRP (if non-inferiority established) | Mean Western Ontario Rotator Cuff Index (WORC) Score The WORC has 21 items in four domains, including physical symptoms (10 questions), sports/recreation/work (4 questions), lifestyle (4 questions) and emotions (3 questions). Raw scores range from 0 to 2100, with a higher score indicating decreased quality of life because of pathological condition of the rotator cuff. | 6 months | 
| assessment of superiority of CTM to PRP (if non-inferiority established) | Mean Western Ontario Rotator Cuff Index (WORC) Score The WORC has 21 items in four domains, including physical symptoms (10 questions), sports/recreation/work (4 questions), lifestyle (4 questions) and emotions (3 questions). Raw scores range from 0 to 2100, with a higher score indicating decreased quality of life because of pathological condition of the rotator cuff. | thru 24 months | 
| assessment of superiority of CTM to PRP (if non-inferiority established) | Visual Analog Scale (VAS) pain scale The Visual Analogue Scale (VAS) measures pain intensity. The VAS consists of a 10cm line, with two end points representing 0 ('no pain') and 10 ('pain as bad as it could possibly be'). | thru 24 months | 
| assessment of superiority of CTM to PRP (if non-inferiority established) | Single Assessment Numeric Evaluation (SANE) The Single Assessment Numeric Evaluation (SANE) is a patient rating from 0-100. Patients rate their current illness score in relation to their pre-injury baseline. SANE scores are most commonly used by orthopedic sports specialist surgeons, and usually for the shoulder and the knee. | thru 24 months | 
| assessment of superiority of CTM to PRP (if non-inferiority established) | American Shoulder and Elbow Surgeons Shoulder (ASES) Score The ASES score is a 10-item measure of shoulder pain and function. Pain is assessed on a 10-cm visual analog scale (VAS) and accounts for 50% of the total score. The remaining 50% of the score is determined by the responses to 10 4-point Likert-scale questions related to physical function | thru 24 months | 
| assessment of superiority of CTM to PRP (if non-inferiority established) | empty can exercise with dumbbell resistance (number of seconds to fatigue) | thru 24 months | 
| assessment of superiority of CTM to PRP (if non-inferiority established) | Side-lying external rotation with dumbbell resistance (number of repetitions in 30 seconds) | thru 24 months | 
| assessment of superiority of CTM to PRP (if non-inferiority established) | Full can exercise with dumbbell resistance (number of repetitions in 60 seconds) | thru 24 months | 
| assessment of superiority of CTM to PRP (if non-inferiority established) | External rotation at 0 and 90 degrees with Thera-Band resistance (number of seconds to fatigue) | thru 24 months | 
| safety of injection of CTM boost compared to PRP | number of adverse events | 6 months | 
| severity of tendinopathy | Magnetic Resonance Imaging (MRI)-based grading scale MRIs will be scored on rubric from 0-5: 0, no tendinopathy; 1, mild tendinopathy; 2, moderate tendinopathy; 3, moderate tendinopathy + partial thickness tear present; 4, severe tendinopathy +partial thickness tear present; 5, severe tendinopathy + full thickness tear present | 6 months | 
| assessment of superiority of CTM to PRP (if non-inferiority established) | serum levels of inflammatory cytokines IL-1β and TNF-α as well as serum level of Fibroblast growth factor (FGF) | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rotator cuff tendinopathy