<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03752034</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00054333</org_study_id>
    <nct_id>NCT03752034</nct_id>
  </id_info>
  <brief_title>Muscle Fiber Fragments for Improved Function of Rotator Cuff Musculature Following Rotator Cuff Repair</brief_title>
  <official_title>Safety of Autologous Muscle Fiber Fragments for Improved Function of Rotator Cuff Musculature Following Rotator Cuff Repair</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wake Forest University Health Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Wake Forest University Health Sciences</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this study, a chest muscle sample (biopsy) will be taken and the muscle fibers will be&#xD;
      removed from the sample and made into smaller strands or fragments. During this same&#xD;
      procedure, those muscle fiber fragments (MFFs) will then be injected directly into the&#xD;
      supraspinatus muscle. Once injected, the MFFs will remain in the supraspinatus where&#xD;
      Investigators believe the MFF will become part of the participants' existing muscle and&#xD;
      provide increased muscle size and strength, improving function (rotator cuff strength and&#xD;
      stability).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Muscle fiber fragment (MFF) therapy has shown pre-clinical and clinical promise in the&#xD;
      treatment of bladder neck insufficiency/incompetent outlet. Fragmentation of muscle fibers&#xD;
      derived from autologous muscle tissue can be injected through a needle into the sphincter&#xD;
      region. The injected muscle fibers are able to assemble into long muscle fibers in the&#xD;
      direction of host muscle fibers. More importantly, muscle progenitor cells residing on the&#xD;
      fragmented muscle fibers survive and integrate into host vasculature and nerve to restore&#xD;
      damaged muscle function. Preclinical results indicate that this technology can be used to&#xD;
      repair and restore damaged sphincter function in urinary incontinence. The development of an&#xD;
      autologous, readily available muscle fiber fragment treatment that may involve less risk and&#xD;
      recovery time than those associated with the standard surgical therapies and urethral bulking&#xD;
      agents, could alter the treatment paradigm of urinary incontinence. The study team&#xD;
      hypothesizes that injected MFFs will incorporate into skeletal muscle and re-assemble along&#xD;
      the fiber direction. The Investigators anticipate that the MFFs can safely be injected into&#xD;
      the atrophied rotator cuff muscle and will help restore the functional contractile properties&#xD;
      of the supraspinatus muscle following rotator cuff repair.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 4, 2019</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Adverse Events</measure>
    <time_frame>6 months post surgery</time_frame>
    <description>The incidence of adverse events will be documented in the areas of product related, biopsy procedure-related, and injection-related reporting for each group.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Fat Free Muscle Volume</measure>
    <time_frame>Month 1, Month 6</time_frame>
    <description>Fat-free muscle volume (total muscle volume minus % of fatty infiltration).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Goutallier Score via MRI 1.5+ image analysis</measure>
    <time_frame>12 weeks, 6 months post operatively</time_frame>
    <description>Measured by MRI T1 Sagittal image at the Y position. Total score values 0- 4 (Grade 0 =normal muscle; Grade 1 =Muscle that contain some fatty streaks; Grade 2 = Fatty infiltration but more muscle than fat; Grade 3 = Equal amounts of fat and muscle; Grade 4 = More fat than muscle.) Lower values denotes better outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Constant Score</measure>
    <time_frame>12 weeks, 6 months post operatively</time_frame>
    <description>The constant score, a 0-100 point scale with 100 being Normal and Abnormal Side &gt;30 Poor, 21-30 Fair, 11-20 Good and &lt;11 Excellent will measure muscle recovery including strength and level of atrophy. Higher scores denote worse outcome measures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ASES Shoulder Score</measure>
    <time_frame>12 weeks, 6 months post operatively</time_frame>
    <description>The ASES Shoulder Score (scale with a max of 100 which is normal function with no pain to minimum of 0 which is extreme pain) will measure muscle recovery. Higher scores denote better outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dynamometer measurements</measure>
    <time_frame>12 weeks, 6 months post operatively</time_frame>
    <description>Measurement will be on a scale used to measure the number of pounds or kilograms generated with arm at 90 degrees of abduction with the elbow extended.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Rotator Cuff</condition>
  <arm_group>
    <arm_group_label>Muscle Fiber Fragments (MFF)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants undergoing rotator cuff repair will have autologous muscle tissue harvested. The tissue will be processed to obtain Muscle Fiber Fragments (MFFs) and administered via direct injection into the supraspinatus muscle belly.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Muscle Fiber Fragments (MFFs)</intervention_name>
    <description>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.</description>
    <arm_group_label>Muscle Fiber Fragments (MFF)</arm_group_label>
    <other_name>Autologous</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males and females, ages 40 to 80 years&#xD;
&#xD;
          -  Unilateral Disease&#xD;
&#xD;
          -  &lt; 1.5cm tear&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diabetes&#xD;
&#xD;
          -  Peripheral Neuropathy&#xD;
&#xD;
          -  Previous Shoulder Surgery&#xD;
&#xD;
          -  Pain Syndrome; cuff arthroplasty&#xD;
&#xD;
          -  Major co-morbidities including, but not limited to, uncontrolled diabetes,&#xD;
             cardiovascular, pulmonary, GI, coagulopathies&#xD;
&#xD;
          -  Arthritis of Shoulder&#xD;
&#xD;
          -  Unwilling or unable to comply with post-operative instructions or follow-up visits&#xD;
&#xD;
          -  Auto Immune Disease&#xD;
&#xD;
          -  Complete Subscapularis Tear&#xD;
&#xD;
          -  Teres Minor involvement&#xD;
&#xD;
          -  History of testing positive for HIV, Hep B, Hep C, HTLV-1, HTLV-2&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Implanted devices containing ferromagnetic material&#xD;
&#xD;
          -  Any implanted electrical stimulation devices (i.e. cochlear implant, defibrillator)&#xD;
&#xD;
          -  Any other condition which the PI feels would be not in the best interest for the&#xD;
             patient or the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gary G Poehling, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wake Forest University Health Sciences</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mary-Clare Day, RN</last_name>
    <phone>336-713-1343</phone>
    <email>mday@wakehealth.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Wake Forest University Health Sciences</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mary-Claire Day, RN</last_name>
      <phone>336-713-1343</phone>
      <email>mday@wakehealth.edu</email>
    </contact>
    <investigator>
      <last_name>Gary G Poehling, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <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>
    <PMID>24845686</PMID>
  </reference>
  <reference>
    <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>
    <PMID>22236637</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>18782310</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>13768451</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>14980519</PMID>
  </reference>
  <reference>
    <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>
    <PMID>2643055</PMID>
  </reference>
  <reference>
    <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>
    <PMID>12728313</PMID>
  </reference>
  <reference>
    <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>
    <PMID>10517639</PMID>
  </reference>
  <reference>
    <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>
    <PMID>12805561</PMID>
  </reference>
  <reference>
    <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>
    <PMID>19500482</PMID>
  </reference>
  <reference>
    <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>
    <PMID>14557752</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>23618586</PMID>
  </reference>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>November 21, 2018</study_first_submitted>
  <study_first_submitted_qc>November 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <last_update_submitted>May 1, 2023</last_update_submitted>
  <last_update_submitted_qc>May 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Muscle Fiber Fragments</keyword>
  <keyword>Rotator Cuff Musculature</keyword>
  <keyword>Rotator Cuff Repair</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03752034
org study id: IRB00054333
nct id: NCT03752034
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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).
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Adverse Events
time frame: 6 months post surgery
description: The incidence of adverse events will be documented in the areas of product related, biopsy procedure-related, and injection-related reporting for each group.
measure: Fat Free Muscle Volume
time frame: Month 1, Month 6
description: Fat-free muscle volume (total muscle volume minus % of fatty infiltration).
measure: Goutallier Score via MRI 1.5+ image analysis
time frame: 12 weeks, 6 months post operatively
description: Measured by MRI T1 Sagittal image at the Y position. Total score values 0- 4 (Grade 0 =normal muscle; Grade 1 =Muscle that contain some fatty streaks; Grade 2 = Fatty infiltration but more muscle than fat; Grade 3 = Equal amounts of fat and muscle; Grade 4 = More fat than muscle.) Lower values denotes better outcomes.
measure: Constant Score
time frame: 12 weeks, 6 months post operatively
description: The constant score, a 0-100 point scale with 100 being Normal and Abnormal Side >30 Poor, 21-30 Fair, 11-20 Good and <11 Excellent will measure muscle recovery including strength and level of atrophy. Higher scores denote worse outcome measures.
measure: ASES Shoulder Score
time frame: 12 weeks, 6 months post operatively
description: The ASES Shoulder Score (scale with a max of 100 which is normal function with no pain to minimum of 0 which is extreme pain) will measure muscle recovery. Higher scores denote better outcomes.
measure: Dynamometer measurements
time frame: 12 weeks, 6 months post operatively
description: Measurement will be on a scale used to measure the number of pounds or kilograms generated with arm at 90 degrees of abduction with the elbow extended.
arm group label: Muscle Fiber Fragments (MFF)
arm group type: Experimental
description: Participants undergoing rotator cuff repair will have autologous muscle tissue harvested. The tissue will be processed to obtain Muscle Fiber Fragments (MFFs) and administered via direct injection into the supraspinatus muscle belly.
intervention type: Other
intervention name: Muscle Fiber Fragments (MFFs)
description: 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.
arm group label: Muscle Fiber Fragments (MFF)
other name: Autologous
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
last name: Gary G Poehling, MD
role: Principal Investigator
affiliation: Wake Forest University Health Sciences
last name: Mary-Clare Day, RN
phone: 336-713-1343
email: mday@wakehealth.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
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.
PMID: 24845686
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.
PMID: 22236637
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.
PMID: 18782310
citation: 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
citation: 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
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.
PMID: 2643055
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.
PMID: 12728313
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.
PMID: 10517639
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.
PMID: 12805561
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.
PMID: 19500482
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.
PMID: 14557752
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.
PMID: 23618586
responsible party type: Sponsor
sharing ipd: No