Clinical trial NCT04325789: Rotator Cuff Healing Using a Nanofiber Scaffold in Patients Greater Than 55 Years
Official title: A Prospective Randomized Multicenter Evaluation of Rotator Cuff Healing Using a Nanofiber Scaffold in Patients Greater Than 55 Years
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Rotator Cuff Tears
Full-thickness Rotator Cuff Tears
Keywords: healing
regenerative medicine
interpositional matrix
synthetic scaffold
full-thickness rotator cuff tear
enthesis regeneration
Lead sponsor: Nanofiber Solutions
Sponsor class: INDUSTRY
First posted: 2020-03-30
Enrollment: 91
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Use of the nanofiber scaffold, in addition to SOC, during the rotator cuff repair is the intervention in this study. Study participants will be randomized into either the treatment or the control group. The control group will undergo routine rotator cuff repair without the scaffold to determine if improved healing is demonstrated with the graft.

Group 1 (control) Group 2 (nanofiber scaffold)
Primary purpose: TREATMENT

Brief summary: Randomized controlled trial of patients over the age of 55 treated with and without a nanofiber scaffold during rotator cuff repair.

Detailed description: 1. INTRODUCTION

   This document is a protocol for a human research study. This study is to be conducted according to United States standards of Good Clinical Practice in accordance with applicable Federal regulations and institutional research policies and procedures.

   Despite numerous advancements in surgical techniques and over 250,000 procedures currently performed annually in the United States, failure of tendon healing following rotator cuff surgery occurs frequently with reports as high as 94%. Nonhealing can lead to persistent pain, poor outcomes, and a significant economic burden to society when revision surgery is required. Several factors have been associated with poor tendon healing with age greater than 60 years shown to be a significant risk factor due to diminishing vascularity at the bone tendon interface where the tear typically originates. While numerous techniques have been devised to improve fixation over the past several decades, very few have been developed to address or enhance the biology at the repair site. Rotium nanofiber is a recent FDA approved scaffold (FDA 510(K) #K183236) that has been shown to improve tendon healing to bone in animal studies. It works to mimic the extracellular matrix and helps concentrates and bind cells at the repair site providing a better organizational structure of the healing tissue. The purpose of the current study is to assess if use of the scaffold significantly improves rotator cuff healing and enhances strength in patients at higher risk of perioperative failure of the repair.
2. BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE

   Rotator cuff tears are a frequent cause of shoulder pain and disability in the elderly population. Typically, when conservative measures fail, surgery is often advised. A successful clinical outcome is felt to be heavily predicated on healing of the tendon to the bone. Despite numerous surgical and technical advancements over the past two decades not all repairs heal, with re-tear, or failure-to-heal, remaining the number one complication associated with rotator cuff surgery. This in turn creates a hefty economic burden on society whereupon surgeries are being performed with poor eventual outcomes and ultimately wasted resources.

   While reasons for failure are multifactorial, a strong correlation has been associated with advancing age. In an observational study on the natural history of rotator cuff disease, patients younger than 50 years old rarely had rotator cuff tears whereas those greater than 60 had a statistically significant greater incidence of unilateral and bilateral tears. Advancing age is believed to alter and change the intrinsic properties of the tendon leading to stiffness, hypovascularity and overall impairment of the biology of tendon healing. Furthermore, when repairs fail, they typically do so within the first four months of surgery. Means, therefore, to enhance the zone of the repair by increasing the cellularity immediately following surgery may improve the overall healing and lessen failures.

   Recently, nanofiber scaffolds have demonstrated the ability to mimic the extracellular matrix and help structure, organize, and proliferate cellular material. They do so by working, in essence, like a sponge when incorporated into the repair site, helping to bind, organize, and promote cell migration. This in effect, creates a less haphazard arrangement and induces better organization of healing tissue at the cellular level. Rotium, is an FDA-approved, nonwoven, microfiber matrix composed of PLCL (poly L-lactide-co-caprolactone) and PGL (polyglycolide) that is indicated for use in rotator cuff repair to enhance healing at the bone tendon interface. The implant is inserted under the rotator cuff tendon and placed on top of the greater tuberosity at the time of surgery and typically positioned over a suture. In a recent animal study performed at Colorado State University, a nearly 75% increased strength of repair was demonstrated at twelve weeks in those tendons treated with the graft. This will be the first prospective randomized clinical study in humans assessing for a difference in healing and strength in a population of patients considered at high risk for postoperative failure of the repair.
3. STUDY OBJECTIVES

Utilizing a randomized controlled trial, this study seeks to evaluate if there is a difference in post-operative healing, strength, and functional outcomes in patients older than 55 years with rotator cuff tears treated with and without the nanofiber scaffold.

Eligibility criteria: Inclusion Criteria:

1. Age 55 and older
2. Able to provide informed consent
3. Primary diagnosis of rotator cuff tear

Exclusion Criteria:

1. Revision rotator cuff surgery
2. Partial thickness rotator cuff tears
3. Massive (greater than 5cm) rotator cuff tears
4. Patients with current tobacco history

Primary outcomes:
measure: Failure of the repair
timeFrame: 24 months
Secondary outcomes:
measure: Change in shoulder range of motion
timeFrame: Preoperative, 6 weeks, 3 months, 6 months, 12 months, 24 months postoperative
measure: Change in isometric rotator cuff muscle strength peak force
timeFrame: Preoperative, 3 months, 6 months, 12 months, 24 months postoperative
measure: Change in patient-reported American Shoulder and Elbow Scores
timeFrame: Preoperative, 2 weeks, 6 weeks, 3 months, 6 months, 12 months, 24 months postoperative
measure: Change in patient-reported postoperative pain (Visual Analogue Scale - Pain)
timeFrame: Preoperative, 2 weeks, 6 weeks, 3 months, 6 months, 12 months, 24 months postoperative
measure: Change in patient-reported Single Assessment Numeric Evaluation (SANE) score
timeFrame: Preoperative, 2 weeks, 6 weeks, 3 months, 6 months, 12 months, 24 months postoperative
measure: Change in patient-reported Veteran Rand 12 (VR-12) score
timeFrame: Preoperative, 2 weeks, 6 weeks, 3 months, 6 months, 12 months, 24 months postoperative
Other outcomes:
Locations:
city: Fishers
country: United States
facility: Central Indiana Orthopedics
state: Indiana
city: Saint Clair Shores
country: United States
facility: Associated Orthopedists of Detroit
state: Michigan
city: Cincinnati
country: United States
facility: The Christ Hospital & The Lindner Reseach Center at The Christ Hospital
state: Ohio
city: Greenville
country: United States
facility: Steadman Hawkins Clinic of the Carolinas - Patewood
state: South Carolina
Study officials:
affiliation: Central Indiana Orthopedics
name: Brian L Badman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Atreon Orthopedics
name: Elsa I Englund Kayuha, MD
role: STUDY_DIRECTOR
References:
citation: Mather RC 3rd, Koenig L, Acevedo D, Dall TM, Gallo P, Romeo A, Tongue J, Williams G Jr. The societal and economic value of rotator cuff repair. J Bone Joint Surg Am. 2013 Nov 20;95(22):1993-2000. doi: 10.2106/JBJS.L.01495.
citation: Harryman DT 2nd, Hettrich CM, Smith KL, Campbell B, Sidles JA, Matsen FA 3rd. A prospective multipractice investigation of patients with full-thickness rotator cuff tears: the importance of comorbidities, practice, and other covariables on self-assessed shoulder function and health status. J Bone Joint Surg Am. 2003 Apr;85(4):690-6.
citation: Iannotti JP, Deutsch A, Green A, Rudicel S, Christensen J, Marraffino S, Rodeo S. Time to failure after rotator cuff repair: a prospective imaging study. J Bone Joint Surg Am. 2013 Jun 5;95(11):965-71. doi: 10.2106/JBJS.L.00708.
citation: Agudelo-Garcia PA, De Jesus JK, Williams SP, Nowicki MO, Chiocca EA, Liyanarachchi S, Li PK, Lannutti JJ, Johnson JK, Lawler SE, Viapiano MS. Glioma cell migration on three-dimensional nanofiber scaffolds is regulated by substrate topography and abolished by inhibition of STAT3 signaling. Neoplasia. 2011 Sep;13(9):831-40. doi: 10.1593/neo.11612.
citation: Teunis T, Lubberts B, Reilly BT, Ring D. A systematic review and pooled analysis of the prevalence of rotator cuff disease with increasing age. J Shoulder Elbow Surg. 2014 Dec;23(12):1913-1921. doi: 10.1016/j.jse.2014.08.001.
citation: Le BT, Wu XL, Lam PH, Murrell GA. Factors predicting rotator cuff retears: an analysis of 1000 consecutive rotator cuff repairs. Am J Sports Med. 2014 May;42(5):1134-42. doi: 10.1177/0363546514525336. Epub 2014 Apr 18.
citation: Diebold G, Lam P, Walton J, Murrell GAC. Relationship Between Age and Rotator Cuff Retear: A Study of 1,600 Consecutive Rotator Cuff Repairs. J Bone Joint Surg Am. 2017 Jul 19;99(14):1198-1205. doi: 10.2106/JBJS.16.00770.
citation: Gulotta LV, Nho SJ, Dodson CC, Adler RS, Altchek DW, MacGillivray JD; HSS Arthroscopic Rotator Cuff Registry. Prospective evaluation of arthroscopic rotator cuff repairs at 5 years: part II--prognostic factors for clinical and radiographic outcomes. J Shoulder Elbow Surg. 2011 Sep;20(6):941-6. doi: 10.1016/j.jse.2011.03.028. Epub 2011 Jun 29.
citation: Liem D, Lichtenberg S, Magosch P, Habermeyer P. Magnetic resonance imaging of arthroscopic supraspinatus tendon repair. J Bone Joint Surg Am. 2007 Aug;89(8):1770-6. doi: 10.2106/JBJS.F.00749.
citation: Koh KH, Kang KC, Lim TK, Shon MS, Yoo JC. Prospective randomized clinical trial of single- versus double-row suture anchor repair in 2- to 4-cm rotator cuff tears: clinical and magnetic resonance imaging results. Arthroscopy. 2011 Apr;27(4):453-62. doi: 10.1016/j.arthro.2010.11.059.
citation: Boileau P, Brassart N, Watkinson DJ, Carles M, Hatzidakis AM, Krishnan SG. Arthroscopic repair of full-thickness tears of the supraspinatus: does the tendon really heal? J Bone Joint Surg Am. 2005 Jun;87(6):1229-40. doi: 10.2106/JBJS.D.02035.
citation: Tempelhof S, Rupp S, Seil R. Age-related prevalence of rotator cuff tears in asymptomatic shoulders. J Shoulder Elbow Surg. 1999 Jul-Aug;8(4):296-9. doi: 10.1016/s1058-2746(99)90148-9.
citation: Bishop J, Klepps S, Lo IK, Bird J, Gladstone JN, Flatow EL. Cuff integrity after arthroscopic versus open rotator cuff repair: a prospective study. J Shoulder Elbow Surg. 2006 May-Jun;15(3):290-9. doi: 10.1016/j.jse.2005.09.017.
citation: Tashjian RZ, Hollins AM, Kim HM, Teefey SA, Middleton WD, Steger-May K, Galatz LM, Yamaguchi K. Factors affecting healing rates after arthroscopic double-row rotator cuff repair. Am J Sports Med. 2010 Dec;38(12):2435-42. doi: 10.1177/0363546510382835. Epub 2010 Oct 28.
citation: Thomazeau H, Boukobza E, Morcet N, Chaperon J, Langlais F. Prediction of rotator cuff repair results by magnetic resonance imaging. Clin Orthop Relat Res. 1997 Nov;(344):275-83.
citation: Kim KC, Shin HD, Lee WY. Repair integrity and functional outcomes after arthroscopic suture-bridge rotator cuff repair. J Bone Joint Surg Am. 2012 Apr 18;94(8):e48. doi: 10.2106/JBJS.K.00158.
citation: Boehm TD, Werner A, Radtke S, Mueller T, Kirschner S, Gohlke F. The effect of suture materials and techniques on the outcome of repair of the rotator cuff: a prospective, randomised study. J Bone Joint Surg Br. 2005 Jun;87(6):819-23. doi: 10.1302/0301-620X.87B6.15638.
citation: Charousset C, Grimberg J, Duranthon LD, Bellaiche L, Petrover D. Can a double-row anchorage technique improve tendon healing in arthroscopic rotator cuff repair?: A prospective, nonrandomized, comparative study of double-row and single-row anchorage techniques with computed tomographic arthrography tendon healing assessment. Am J Sports Med. 2007 Aug;35(8):1247-53. doi: 10.1177/0363546507301661. Epub 2007 Apr 23.
citation: Deutsch A, Kroll DG, Hasapes J, Staewen RS, Pham C, Tait C. Repair integrity and clinical outcome after arthroscopic rotator cuff repair using single-row anchor fixation: a prospective study of single-tendon and two-tendon tears. J Shoulder Elbow Surg. 2008 Nov-Dec;17(6):845-52. doi: 10.1016/j.jse.2008.04.004. Epub 2008 Aug 20.
citation: Franceschi F, Ruzzini L, Longo UG, Martina FM, Zobel BB, Maffulli N, Denaro V. Equivalent clinical results of arthroscopic single-row and double-row suture anchor repair for rotator cuff tears: a randomized controlled trial. Am J Sports Med. 2007 Aug;35(8):1254-60. doi: 10.1177/0363546507302218. Epub 2007 Jun 6.
citation: Klepps S, Bishop J, Lin J, Cahlon O, Strauss A, Hayes P, Flatow EL. Prospective evaluation of the effect of rotator cuff integrity on the outcome of open rotator cuff repairs. Am J Sports Med. 2004 Oct-Nov;32(7):1716-22. doi: 10.1177/0363546504265262.
citation: Ko SH, Lee CC, Friedman D, Park KB, Warner JJ. Arthroscopic single-row supraspinatus tendon repair with a modified mattress locking stitch: a prospective, randomized controlled comparison with a simple stitch. Arthroscopy. 2008 Sep;24(9):1005-12. doi: 10.1016/j.arthro.2008.04.074. Epub 2008 Jun 24.
citation: Lapner PL, Sabri E, Rakhra K, McRae S, Leiter J, Bell K, Macdonald P. A multicenter randomized controlled trial comparing single-row with double-row fixation in arthroscopic rotator cuff repair. J Bone Joint Surg Am. 2012 Jul 18;94(14):1249-57. doi: 10.2106/JBJS.K.00999.
citation: Lee BG, Cho NS, Rhee YG. Effect of two rehabilitation protocols on range of motion and healing rates after arthroscopic rotator cuff repair: aggressive versus limited early passive exercises. Arthroscopy. 2012 Jan;28(1):34-42. doi: 10.1016/j.arthro.2011.07.012. Epub 2011 Oct 20.
citation: Ma HL, Chiang ER, Wu HT, Hung SC, Wang ST, Liu CL, Chen TH. Clinical outcome and imaging of arthroscopic single-row and double-row rotator cuff repair: a prospective randomized trial. Arthroscopy. 2012 Jan;28(1):16-24. doi: 10.1016/j.arthro.2011.07.003. Epub 2011 Oct 7.
citation: Galatz LM, Ball CM, Teefey SA, Middleton WD, Yamaguchi K. The outcome and repair integrity of completely arthroscopically repaired large and massive rotator cuff tears. J Bone Joint Surg Am. 2004 Feb;86(2):219-24. doi: 10.2106/00004623-200402000-00002.
citation: Jost B, Pfirrmann CW, Gerber C, Switzerland Z. Clinical outcome after structural failure of rotator cuff repairs. J Bone Joint Surg Am. 2000 Mar;82(3):304-14. doi: 10.2106/00004623-200003000-00002.
citation: Liu SH, Baker CL. Arthroscopically assisted rotator cuff repair: correlation of functional results with integrity of the cuff. Arthroscopy. 1994 Feb;10(1):54-60. doi: 10.1016/s0749-8063(05)80293-2.
citation: Akpinar S, Uysal M, Pourbagher MA, Ozalay M, Cesur N, Hersekli MA. Prospective evaluation of the functional and anatomical results of arthroscopic repair in small and medium-sized full-thickness tears of the supraspinatus tendon. Acta Orthop Traumatol Turc. 2011;45(4):248-53. doi: 10.3944/AOTT.2011.2455.
citation: Harryman DT 2nd, Mack LA, Wang KY, Jackins SE, Richardson ML, Matsen FA 3rd. Repairs of the rotator cuff. Correlation of functional results with integrity of the cuff. J Bone Joint Surg Am. 1991 Aug;73(7):982-9.
citation: Mall NA, Kim HM, Keener JD, Steger-May K, Teefey SA, Middleton WD, Stobbs G, Yamaguchi K. Symptomatic progression of asymptomatic rotator cuff tears: a prospective study of clinical and sonographic variables. J Bone Joint Surg Am. 2010 Nov 17;92(16):2623-33. doi: 10.2106/JBJS.I.00506.
citation: Yamaguchi K, Ditsios K, Middleton WD, Hildebolt CF, Galatz LM, Teefey SA. The demographic and morphological features of rotator cuff disease. A comparison of asymptomatic and symptomatic shoulders. J Bone Joint Surg Am. 2006 Aug;88(8):1699-704. doi: 10.2106/JBJS.E.00835.
citation: Cho NS, Rhee YG. The factors affecting the clinical outcome and integrity of arthroscopically repaired rotator cuff tears of the shoulder. Clin Orthop Surg. 2009 Jun;1(2):96-104. doi: 10.4055/cios.2009.1.2.96. Epub 2009 May 30.
citation: Nho SJ, Shindle MK, Adler RS, Warren RF, Altchek DW, MacGillivray JD. Prospective analysis of arthroscopic rotator cuff repair: subgroup analysis. J Shoulder Elbow Surg. 2009 Sep-Oct;18(5):697-704. doi: 10.1016/j.jse.2008.11.018. Epub 2009 Mar 9.
citation: Hein J, Reilly JM, Chae J, Maerz T, Anderson K. Retear Rates After Arthroscopic Single-Row, Double-Row, and Suture Bridge Rotator Cuff Repair at a Minimum of 1 Year of Imaging Follow-up: A Systematic Review. Arthroscopy. 2015 Nov;31(11):2274-81. doi: 10.1016/j.arthro.2015.06.004. Epub 2015 Jul 15.
citation: Fukunishi T, Best CA, Ong CS, Groehl T, Reinhardt J, Yi T, Miyachi H, Zhang H, Shinoka T, Breuer CK, Johnson J, Hibino N. Role of Bone Marrow Mononuclear Cell Seeding for Nanofiber Vascular Grafts. Tissue Eng Part A. 2018 Jan;24(1-2):135-144. doi: 10.1089/ten.TEA.2017.0044. Epub 2017 Jun 13.
citation: Fukunishi T, Best CA, Sugiura T, Opfermann J, Ong CS, Shinoka T, Breuer CK, Krieger A, Johnson J, Hibino N. Preclinical study of patient-specific cell-free nanofiber tissue-engineered vascular grafts using 3-dimensional printing in a sheep model. J Thorac Cardiovasc Surg. 2017 Apr;153(4):924-932. doi: 10.1016/j.jtcvs.2016.10.066. Epub 2016 Nov 14.
citation: Romeo A, Easley J, Regan D, Hackett E, Johnson J, Johnson J, Puttlitz C, McGilvray K. Rotator cuff repair using a bioresorbable nanofiber interposition scaffold: a biomechanical and histologic analysis in sheep. J Shoulder Elbow Surg. 2022 Feb;31(2):402-412. doi: 10.1016/j.jse.2021.07.018. Epub 2021 Aug 25.