Connective Tissue Matrix Compared to Steroid Injections for Rotator Cuff Tendinopathy

Connective Tissue Matrix (CTM) Compared to Corticosteroid Injections: A Pilot Randomized Controlled Trial

The goal of the study is to see which is better at treating patients which rotator cuff tendinopathy (RCT): a single injection of Connective Tissue Matrix boost (CTM) or a steroid shot.

Patients will be randomized (like flipping a coin) to the treatment. Patients and researchers will be blinded (not know) what group the patients are in.

Patients will come back to the study clinic at 6 weeks, 3 months and 6 months after the shot to answer questionnaires, have a physical exam, and complete physical function tests to check their shoulder.

Study Overview

• Status: Withdrawn
• Conditions: Rotator Cuff Tendinopathy
• Intervention / Treatment: Drug: Corticosteroid; Drug: celgene

Detailed Description

CTM vs. Steroid is a double-blind randomized controlled trial. Patients will be randomized to CTM Boost or Kenalog-40 (corticosteroid). Patients will be followed for six months and have three follow-up visits where they will have a physical exam, complete questionnaires, have a physical exam, including physical functional assessments, be screened for adverse events. Data will be collected from their medical chart after each visit.

CTM Boost (CTM Biomedical, Miami, FL) is a tissue allograft derived from decellularized, particulate human placental connective tissue. It is regulated as a minimally-manipulated human cell, tissue, and cellular and tissue-based product (HCT/P) biologic by the FDA and is marketed for homologous use to supplement or replace damaged or inadequate connective tissue. It is implanted via injection into the tissue. CTM Boost is available in a range of volumes. In this study, the 2.0cc volume of CTM Boost will be administered by injection directly into the subacromial space using a 20G needle.

Kenalog-40 is a long-acting corticosteroid injection for intramuscular (into the muscle) or intra-articular (into the joints) use. It may be used to treat many different types of inflammatory conditions. In this study, a 2.0cc dose injection of kenalog-40 will be administered directly into the subacromial space using a 20G needle (for patients randomized to this control arm).

Study Questionnaires are as follows:

• WORC: 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.
• 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.
• VAS: 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).
• ASES: 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

• Functional Assessments: various arm/shoulder exercises with dumbbells, weights or resistance. Time until patient is fatigued and/or number of repetitions will be measured.

  • These tests will include the following:

    • Empty can exercise with dumbbell resistance: Arm held in a position with weighted resistance, while measuring number of seconds to fatigue (or unable to maintain arm at 90 degrees).
    • Side-lying external rotation with dumbbell resistance: Lie on side (opposite shoulder) with weight held in hand, elbow flexed to 90 degrees while rotate through a full range of motion at the shoulder. The number of repetitions during a 30-second period are recorded.

Full can exercise with dumbbell resistance: Stand parallel to wall with the handheld in a fist and shoulder forward flexed parallel to the floor. A measuring stick will be used to measure how far forward on the yardstick patient can reach. The number of repetitions during a 60-second period are recorded.

External rotation of shoulder at 0 and 90 degrees with Thera-Band resistance. Patient will be instructed to perform rapid swinging motions in a 30-degree arc until fatigued.

Safety Evaluation:

• Infection
• Tear of the tendon
• Shoulder stiffness
• Admission to the hospital for a shoulder-related issue
• Surgical rotator cuff repair or subacromial decompression.

Data collected from a medical record review:

MRN Age Gender Weight Height Comorbidities Duration of symptoms Smoking status Diabetes Shoulder imaging reports from pre-enrollment MRI/xray Progress/Office notes Concomitant Medication

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Health Network Federal North Medical Office Building

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 corticosteroid 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 a history of chronic steroid treatment for any medical reason

• Patients with medical conditions that may affect healing, such as

  • End-stage renal disease
  • Uncontrolled diabetes
  • Peripheral vascular disease
  • Severe and/or systemic immunocompromising conditions such as Lupus or HIV infection
• Patients who are pregnant or breast feeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Corticosteroid; Kenalog-40 is a long-acting corticosteroid injection for intramuscular (into the muscle) or intra-articular (into the joints) use. It may be used to treat many different types of inflammatory conditions. In this study, a 2.0cc dose injection of Kenalog-40 will be administered directly into the subacromial space using a 20G needle. 3mL of ropivacaine will be injected along with the steroid (as part of the same injection). Posttreatment pain control (hydrocodone/acetaminophen #20 5/500 mg) will be used.	Drug: Corticosteroid; Kenalog-40 is a long-acting corticosteroid injection for intramuscular (into the muscle) or intra-articular (into the joints) use. It may be used to treat many different types of inflammatory conditions. In this study, a 2.0cc dose injection of Kenalog-40 will be administered directly into the subacromial space using a 20G needle. 3mL of ropivacaine will be injected along with the steroid (as part of the same injection). Posttreatment pain control (hydrocodone/acetaminophen #20 5/500 mg) will be used.; Other Names: kenalog
Experimental: CTM Boost; TM Boost (CTM Biomedical, Miami, FL) is a decellularized Human Cellular and Tissue Based Allograft (HCT/P) derived from placental connective tissue. It is marketed as an allograft for homologous use to supplement or replace damaged or inadequate connective tissue. It is regulated as a minimally-manipulated biologic by the FDA and is marketed as an allograft for homologous use to supplement or replace damaged or inadequate connective tissue. It is administered applied into the tissue via injection. Participant will undergo a single injection of 2.0cc of the injectable CTM allograft, administered using a 20G needle in the subacromial space. 3mL of ropivacaine will be mixed into the syringe prior to administration of the injection. Posttreatment pain control (hydrocodone/acetaminophen #20 5/500 mg) will be used.	Drug: celgene; CTM Boost (CTM Biomedical, Miami, FL) is a decellularized Human Cellular and Tissue Based Allograft (HCT/P) derived from placental connective tissue. It is marketed as an allograft for homologous use to supplement or replace damaged or inadequate connective tissue. It is regulated as a minimally-manipulated biologic by the FDA and is marketed as an allograft for homologous use to supplement or replace damaged or inadequate connective tissue. It is administered applied into the tissue via injection. Participant will undergo a single injection of 2.0cc of the injectable CTM allograft, administered using a 20G needle in the subacromial space. 3mL of ropivacaine will be mixed into the syringe prior to administration of the injection. Posttreatment pain control (hydrocodone/acetaminophen #20 5/500 mg) will be used.; Other Names: CTM boost

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Raw WORC Score at 3 Month Visit	The primary outcome will be raw WORC score at the Month 3 visit. WORC is a patient-reported quality of life outcome measure for patients with rotator cuff disorders. The raw score obtained from scoring a completed questionnaire ranges from 0 to 2100, where higher scores indicate poorer quality of life.	3 Month Visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WORC Score	WORC: 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.	Baseline, Week 6, Month 3, Month 6 Visits
VAS: The Visual Analogue Scale	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')	Baseline, Week 6, Month 3, Month 6 Visits
SANE: The Single Assessment Numeric Evaluation	The SANEpatient 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.	Baseline, Week 6, Month 3, Month 6 Visits
ASES	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	Baseline, Week 6, Month 3, Month 6 Visits
Functional Assessments: Empty can exercise	Empty can exercise with dumbbell resistance: Arm held in a position with weighted resistance, while measuring number of seconds to fatigue (or unable to maintain arm at 90 degrees). Time until patient is fatigued	Baseline, Week 6, Month 3, Month 6 Visits
Functional Assessments: External Rotation with Dumbell	Side-lying external rotation with dumbbell resistance: Lie on side (opposite shoulder) with weight held in hand, elbow flexed to 90 degrees while rotate through a full range of motion at the shoulder. The number of repetitions during a 30-second period are recorded.	Baseline, Week 6, Month 3, Month 6 Visits
Functional Assessments: Full can exercise with dumbbell resistance	Stand parallel to wall with the handheld in a fist and shoulder forward flexed parallel to the floor. A measuring stick will be used to measure how far forward on the yardstick patient can reach. The number of repetitions during a 60-second period are recorded.	Baseline, Week 6, Month 3, Month 6 Visits
Functional Assessments: External rotation of shoulder at 0 and 90 degrees with Thera-Band resistance	Patient will be instructed to perform rapid swinging motions in a 30-degree arc until fatigued.	Baseline, Week 6, Month 3, Month 6 Visits
Safety Evaluations; Adverse Events; Serious Adverse Events	Infection; Tear of the tendon; Shoulder stiffness; Admission to the hospital for a shoulder-related issue; Surgical rotator cuff repair or subacromial decompression.	Week 6, Month 3, Month 6 Visits

Collaborators and Investigators

• Sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
• Collaborators: CTM Biomedical

Publications and helpful links

General Publications

• Giovannetti de Sanctis E, Franceschetti E, De Dona F, Palumbo A, Paciotti M, Franceschi F. The Efficacy of Injections for Partial Rotator Cuff Tears: A Systematic Review. J Clin Med. 2020 Dec 25;10(1):51. doi: 10.3390/jcm10010051.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2024
• Primary Completion (Actual): December 17, 2025
• Study Completion (Actual): December 17, 2025

Study Registration Dates

• First Submitted: November 25, 2024
• First Submitted That Met QC Criteria: November 26, 2024
• First Posted (Actual): December 2, 2024

Study Record Updates

• Last Update Posted (Actual): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Shoulder; Tendinopathy; Rotator cuff
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Muscular Diseases; Wounds and Injuries; Tendon Injuries; Tendinopathy; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Triamcinolone; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Triamcinolone Acetonide; Adrenal Cortex Hormones
• Other Study ID Numbers: 2024-118

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