Clinical trial NCT03752034: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Rotator Cuff
Keywords: Muscle Fiber Fragments
Rotator Cuff Musculature
Rotator Cuff Repair
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2018-11-23
Enrollment: 20
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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

Primary outcomes:
measure: Incidence of Adverse Events
timeFrame: 6 months post surgery
measure: Incidence of Adverse Events
timeFrame: 12 months post surgery
Secondary outcomes:
measure: Fat Free Muscle Volume
timeFrame: Month 1, Month 6, and Month 12
measure: Goutallier Score via MRI 1.5+ image analysis
timeFrame: 12 weeks, 6 months, and 12 months post operatively
measure: Constant Score
timeFrame: 12 weeks, 6 months, and 12 months post operatively
measure: ASES Shoulder Score
timeFrame: 12 weeks, 6 months, and 12 months post operatively
measure: Dynamometer measurements
timeFrame: 12 weeks, 6 months, and 12 months post operatively
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Gary G Poehling, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
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citation: 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.
citation: 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.
citation: 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.
citation: Leobon B, Garcin I, Menasche P, Vilquin JT, Audinat E, Charpak S. Myoblasts transplanted into rat infarcted myocardium are functionally isolated from their host. Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7808-11. doi: 10.1073/pnas.1232447100. Epub 2003 Jun 12.
citation: Seidel M, Borczynska A, Rozwadowska N, Kurpisz M. Cell-based therapy for heart failure: skeletal myoblasts. Cell Transplant. 2009;18(7):695-707. doi: 10.3727/096368909X470810. Epub 2009 Apr 6.
citation: Yiou R, Yoo JJ, Atala A. Restoration of functional motor units in a rat model of sphincter injury by muscle precursor cell autografts. Transplantation. 2003 Oct 15;76(7):1053-60. doi: 10.1097/01.TP.0000090396.71097.C2.
citation: Badra S, Andersson KE, Dean A, Mourad S, Williams JK. Long-term structural and functional effects of autologous muscle precursor cell therapy in a nonhuman primate model of urinary sphincter deficiency. J Urol. 2013 Nov;190(5):1938-45. doi: 10.1016/j.juro.2013.04.052. Epub 2013 Apr 22.