Connective Tissue Matrix for Rotator Cuff Tendinopathy (CTM RCT)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Tendinopathy; Shoulder Pain; Rotator Cuff Tendinitis; Rotator Cuff Tendinosis
• Intervention / Treatment: Biological: CTM Boost; Biological: PRP

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Health Network Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Health Network Federal North Medical Office Building
    • Wexford, Pennsylvania, United States, 15090
      • AHN Wexford Hospital
    • Wexford, Pennsylvania, United States, 15090
      • AHN Wexford Health & Wellness Pavilion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CTM Treatment; 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; 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.
Active Comparator: PRP Treatment; Each participant randomized to this arm will receive a single injection of Platelet Rich Plasma (PRP).	Biological: PRP; 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.

What is the study measuring?

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
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
Mean Western Ontario Rotator Cuff Index (WORC) Score	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.	at 6 months
assessment of superiority of CTM to PRP (if non-inferiority established)/ WORC Score	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.	Each visit up to 24 months
assessment of superiority of CTM to PRP (if non-inferiority established) / VAS Pain Scale	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').	Each visit up to 24 months
assessment of superiority of CTM to PRP (if non-inferiority established) / SANE	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.	Each visit up to 24 months
assessment of superiority of CTM to PRP (if non-inferiority established) / ASES	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	Each visit up to 24 months
assessment of superiority of CTM to PRP (if non-inferiority established) / empty can exercise	empty can exercise with dumbbell resistance (number of seconds to fatigue)	Each visit up to 24 months
assessment of superiority of CTM to PRP (if non-inferiority established) / side laying external rotation with dumbbell resistance	Side-lying external rotation with dumbbell resistance (number of repetitions in 30 seconds)	Each visit up to 24 months
assessment of superiority of CTM to PRP (if non-inferiority established) / full can with dumbbell resistance	Full can exercise with dumbbell resistance (number of repetitions in 60 seconds)	Each visit up to 24 months
assessment of superiority of CTM to PRP (if non-inferiority established) / external rotation at 0 and 90 degrees	External rotation at 0 and 90 degrees with Thera-Band resistance (number of seconds to fatigue)	Each visit up to 24 months

Collaborators and Investigators

• Sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
• Collaborators: Connective Tissue Matrix Biomedical, LLC
• Investigators: Principal Investigator: Patrick Demeo, MD, Allegheny Health Network

Publications and helpful links

General Publications

• Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007 May;39(2):175-91. doi: 10.3758/bf03193146.
• A Hamid MS, Sazlina SG. Platelet-rich plasma for rotator cuff tendinopathy: A systematic review and meta-analysis. PLoS One. 2021 May 10;16(5):e0251111. doi: 10.1371/journal.pone.0251111. eCollection 2021.
• Lin MT, Wei KC, Wu CH. Effectiveness of Platelet-Rich Plasma Injection in Rotator Cuff Tendinopathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Diagnostics (Basel). 2020 Mar 28;10(4):189. doi: 10.3390/diagnostics10040189.
• Gotoh M, Hamada K, Yamakawa H, Yanagisawa K, Nakamura M, Yamazaki H, Ueyama Y, Tamaoki N, Inoue A, Fukuda H. Interleukin-1-induced subacromial synovitis and shoulder pain in rotator cuff diseases. Rheumatology (Oxford). 2001 Sep;40(9):995-1001. doi: 10.1093/rheumatology/40.9.995.
• Gotoh M, Hamada K, Yamakawa H, Nakamura M, Yamazaki H, Ueyama Y, Tamaoki N, Inoue A, Fukuda H. Perforation of rotator cuff increases interleukin 1beta production in the synovium of glenohumeral joint in rotator cuff diseases. J Rheumatol. 2000 Dec;27(12):2886-92.
• Yanagisawa K, Hamada K, Gotoh M, TokunagaT, Oshika Y, Tomisawa M, Lee YH, Handa A, Kijima H, Yamazaki H, Nakamura M, Ueyama Y, Tamaoki N, Fukuda H. Vascular endothelial growth factor (VEGF) expression in the subacromial bursa is increased in patients with impingement syndrome. J Orthop Res. 2001 May;19(3):448-55. doi: 10.1016/S0736-0266(00)90021-4.
• Sachinis NP, Yiannakopoulos CK, Chalidis B, Kitridis D, Givissis P. Biomolecules Related to Rotator Cuff Pain: A Scoping Review. Biomolecules. 2022 Jul 22;12(8):1016. doi: 10.3390/biom12081016.
• Dean BJ, Snelling SJ, Dakin SG, Murphy RJ, Javaid MK, Carr AJ. Differences in glutamate receptors and inflammatory cell numbers are associated with the resolution of pain in human rotator cuff tendinopathy. Arthritis Res Ther. 2015 Jul 10;17(1):176. doi: 10.1186/s13075-015-0691-5.
• Chen J, Svensson J, Sundberg CJ, Ahmed AS, Ackermann PW. FGF gene expression in injured tendons as a prognostic biomarker of 1-year patient outcome after Achilles tendon repair. J Exp Orthop. 2021 Mar 11;8(1):20. doi: 10.1186/s40634-021-00335-0.
• Scarpone M, Rabago D, Snell E, Demeo P, Ruppert K, Pritchard P, Arbogast G, Wilson JJ, Balzano JF. Effectiveness of Platelet-rich Plasma Injection for Rotator Cuff Tendinopathy: A Prospective Open-label Study. Glob Adv Health Med. 2013 Mar;2(2):26-31. doi: 10.7453/gahmj.2012.054.
• Braun C, Handoll HH. Estimating the Minimal Important Difference for the Western Ontario Rotator Cuff Index (WORC) in adults with shoulder pain associated with partial-thickness rotator cuff tears. Musculoskelet Sci Pract. 2018 Jun;35:30-33. doi: 10.1016/j.msksp.2018.02.003. Epub 2018 Feb 12.
• Bushnell BD, Bishai SK, Krupp RJ, McMillan S, Schofield BA, Trenhaile SW, McIntyre LF. Treatment of Partial-Thickness Rotator Cuff Tears With a Resorbable Bioinductive Bovine Collagen Implant: 1-Year Results From a Prospective Multicenter Registry. Orthop J Sports Med. 2021 Aug 13;9(8):23259671211027850. doi: 10.1177/23259671211027850. eCollection 2021 Aug.

Helpful Links

• Sealed Envelope | Power calculator for continuous outcome non-inferiority trial
• Daines R. LibGuides: Statistics Resources: Partial Eta Squared

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2023
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): January 15, 2028

Study Registration Dates

• First Submitted: November 29, 2023
• First Submitted That Met QC Criteria: November 29, 2023
• First Posted (Actual): December 7, 2023

Study Record Updates

• Last Update Posted (Estimated): September 8, 2025
• Last Update Submitted That Met QC Criteria: September 2, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: rotator cuff tendinopathy
• Additional Relevant MeSH Terms: Shoulder Injuries; Pain; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Wounds and Injuries; Joint Diseases; Rupture; Tendon Injuries; Arthralgia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Rotator Cuff Injuries; Shoulder Pain; Tendinopathy
• Other Study ID Numbers: 2023-264-FN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No