Connective Tissue Matrix for Rotator Cuff Tendinopathy

Shoulder Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06160427
• Other study ID #: 2023-264-FN
• Status: Recruiting
• Phase: Phase 4
• Start date: December 4, 2023
• Est. completion date: January 15, 2028

Study information

• Verified date: March 2024
• Source: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
• Contact: Patrick Demeo, MD
• Phone: 412-359-3895
• Email: patrick.demeo[@]ahn.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 92
• Est. completion date: January 15, 2028
• Est. primary completion date: January 15, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Rotator Cuff Injuries
• Rotator Cuff Tendinitis
• Rotator Cuff Tendinosis
• Shoulder Pain
• Tendinopathy

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Allegheny Health Network Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Allegheny Health Network Federal North Medical Office Building	Pittsburgh	Pennsylvania
United States	AHN Wexford Health & Wellness Pavilion	Wexford	Pennsylvania
United States	AHN Wexford Hospital	Wexford	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)	Connective Tissue Matrix Biomedical, LLC

Country where clinical trial is conducted

United States, 

References & Publications (12)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	safety of injection of CTM boost compared to PRP	number of adverse events	6 months
Secondary	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
Secondary	assessment of superiority of CTM to PRP (if non-inferiority established)	serum levels of inflammatory cytokines IL-1ß and TNF-a as well as serum level of Fibroblast growth factor (FGF)	6 months

External Links

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