Muscle Fiber Fragments for Improved Function of Rotator Cuff Musculature Following Rotator Cuff Repair

Official title

Safety of Autologous Muscle Fiber Fragments for Improved Function of Rotator Cuff Musculature Following Rotator Cuff Repair

Overview

In this study, a chest muscle sample (biopsy) will be taken and the muscle fibers will be removed from the sample and made into smaller strands or fragments. During this same procedure, those muscle fiber fragments (MFFs) will then be injected directly into the supraspinatus muscle. Once injected, the MFFs will remain in the supraspinatus where Investigators believe the MFF will become part of the participants' existing muscle and provide increased muscle size and strength, improving function (rotator cuff strength and stability).

Detailed description

Muscle fiber fragment (MFF) therapy has shown pre-clinical and clinical promise in the treatment of bladder neck insufficiency/incompetent outlet. Fragmentation of muscle fibers derived from autologous muscle tissue can be injected through a needle into the sphincter region. The injected muscle fibers are able to assemble into long muscle fibers in the direction of host muscle fibers. More importantly, muscle progenitor cells residing on the fragmented muscle fibers survive and integrate into host vasculature and nerve to restore damaged muscle function. Preclinical results indicate that this technology can be used to repair and restore damaged sphincter function in urinary incontinence. The development of an autologous, readily available muscle fiber fragment treatment that may involve less risk and recovery time than those associated with the standard surgical therapies and urethral bulking agents, could alter the treatment paradigm of urinary incontinence. The study team hypothesizes that injected MFFs will incorporate into skeletal muscle and re-assemble along the fiber direction. The Investigators anticipate that the MFFs can safely be injected into the atrophied rotator cuff muscle and will help restore the functional contractile properties of the supraspinatus muscle following rotator cuff repair.

Interventions

• Other Muscle Fiber Fragments (MFFs)
  During the rotator cuff repair procedure, a biopsy of muscle will be taken from the pectoralis major and processed under sterile conditions in the operating room to obtain MFFs. The final product, composed of autologous MFFs in suspension, will be delivered via targeted injection into the muscle belly of the supraspinatus through the Naviaser Portal with visual guidance after rotator cuff repair is complete.

Primary outcome measures

• Incidence of Adverse Events [Time frame: 6 months post surgery]
• Incidence of Adverse Events [Time frame: 12 months post surgery]

Secondary outcome measures (5)

• Fat Free Muscle Volume [Time frame: Month 1, Month 6, and Month 12]
• Goutallier Score via MRI 1.5+ image analysis [Time frame: 12 weeks, 6 months, and 12 months post operatively]
• Constant Score [Time frame: 12 weeks, 6 months, and 12 months post operatively]
• ASES Shoulder Score [Time frame: 12 weeks, 6 months, and 12 months post operatively]
• Dynamometer measurements [Time frame: 12 weeks, 6 months, and 12 months post operatively]

Eligibility criteria

Inclusion criteria

• Males and females, ages 40 to 80 years
• Unilateral Disease
• < 1.5cm tear

Exclusion criteria

• Diabetes
• Peripheral Neuropathy
• Previous Shoulder Surgery
• Pain Syndrome; cuff arthroplasty
• Major co-morbidities including, but not limited to, uncontrolled diabetes, cardiovascular, pulmonary, GI, coagulopathies
• Arthritis of Shoulder
• Unwilling or unable to comply with post-operative instructions or follow-up visits
• Auto Immune Disease
• Complete Subscapularis Tear
• Teres Minor involvement
• History of testing positive for HIV, Hep B, Hep C, HTLV-1, HTLV-2
• Pregnancy
• Implanted devices containing ferromagnetic material
• Any implanted electrical stimulation devices (i.e. cochlear implant, defibrillator)
• Any other condition which the PI feels would be not in the best interest for the patient or the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Wake Forest University Health Sciences — Winston-Salem

Publications

• Deniz G, Kose O, Tugay A, Guler F, Turan A. Fatty degeneration and atrophy of the rotator cuff muscles after arthroscopic repair: does it improve, halt or deteriorate? Arch Orthop Trauma Surg. 2014 Jul;134(7):985-90. doi: 10.1007/s00402-014-2009-5. Epub 2014 May 21. PMID 24845686
• Eberli D, Aboushwareb T, Soker S, Yoo JJ, Atala A. Muscle precursor cells for the restoration of irreversibly damaged sphincter function. Cell Transplant. 2012;21(9):2089-98. doi: 10.3727/096368911X623835. Epub 2012 Jan 10. PMID 22236637
• Eberli D, Andersson KE, Yoo JJ, Atala A. A canine model of irreversible urethral sphincter insufficiency. BJU Int. 2009 Jan;103(2):248-53. doi: 10.1111/j.1464-410X.2008.08001.x. Epub 2008 Sep 8. PMID 18782310
• MAURO A. Satellite cell of skeletal muscle fibers. J Biophys Biochem Cytol. 1961 Feb;9(2):493-5. doi: 10.1083/jcb.9.2.493. No abstract available. PMID 13768451
• Benchaouir R, Rameau P, Decraene C, Dreyfus P, Israeli D, Pietu G, Danos O, Garcia L. Evidence for a resident subset of cells with SP phenotype in the C2C12 myogenic line: a tool to explore muscle stem cell biology. Exp Cell Res. 2004 Mar 10;294(1):254-68. doi: 10.1016/j.yexcr.2003.11.005. PMID 14980519
• Partridge TA, Morgan JE, Coulton GR, Hoffman EP, Kunkel LM. Conversion of mdx myofibres from dystrophin-negative to -positive by injection of normal myoblasts. Nature. 1989 Jan 12;337(6203):176-9. doi: 10.1038/337176a0. PMID 2643055
• Yiou R, Lefaucheur JP, Atala A. The regeneration process of the striated urethral sphincter involves activation of intrinsic satellite cells. Anat Embryol (Berl). 2003 May;206(6):429-35. doi: 10.1007/s00429-003-0313-x. Epub 2003 May 1. PMID 12728313
• Gussoni E, Soneoka Y, Strickland CD, Buzney EA, Khan MK, Flint AF, Kunkel LM, Mulligan RC. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature. 1999 Sep 23;401(6751):390-4. doi: 10.1038/43919. PMID 10517639

Identifiers

NCT: NCT03752034 · IRB00054333

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗