<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/NCT03749863</url>
  </required_header>
  <id_info>
    <org_study_id>APP-18-05224</org_study_id>
    <nct_id>NCT03749863</nct_id>
  </id_info>
  <brief_title>Serial Platelet-Rich Plasma Injections for Vocal Fold Atrophy, Scar, and/or Sulcus Vocalis</brief_title>
  <official_title>Safety and Efficacy of Serial Platelet-Rich Plasma Injections for Treatment of Vocal Fold Atrophy, Scar, and/or Sulcus Vocalis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Southern California</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Southern California</source>
  <oversight_info>
    <has_dmc>No</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>
      This study will investigate the safety and efficacy of four serial monthly vocal fold&#xD;
      injections of platelet-rich plasma to treat dysphonia secondary to vocal fold atrophy, scar,&#xD;
      and/or sulcus vocalis with glottal insufficiency&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Vocal fold atrophy, scar, sulcus vocalis, glottal insufficiency with resulting dysphonia is a&#xD;
      condition affecting millions of aging Americans, up to 35% of those 65 or older. Currently&#xD;
      used treatment methods include voice therapy, injections of inert fillers, and laryngeal&#xD;
      framework surgery. These modalities are imperfect with voice therapy requiring considerable&#xD;
      time commitment, filler injections generally temporary in benefit, and surgery with increased&#xD;
      risks. The investigators intend to conduct a single-arm study to assess the safety and&#xD;
      efficacy of autologous platelet-rich plasma (PRP) injection for vocal fold atrophy, sulcus&#xD;
      vocalis and scar. PRP is a substance purified from the patient's own blood that consists of&#xD;
      platelets, growth factors, and other regenerative molecules that have been shown to promote&#xD;
      rejuvenation in a variety of tissue types. Patients with vocal fold atrophy, sulcus vocalis,&#xD;
      and scar identified in the USC Voice Center will be offered participation in a study to&#xD;
      receive serial PRP injections in one vocal fold. Outcome measures evaluated pre- and&#xD;
      post-injection and over follow-up visits will include various patient reported quality of&#xD;
      life indices, objective clinical assessments of voice, and laryngeal videostroboscopy&#xD;
      examinations. The investigators hypothesize that serial PRP injections will significantly&#xD;
      improve vocal fold mucosal volume, morphology, and dysphonia in these patients with no&#xD;
      adverse side effects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 18, 2020</start_date>
  <completion_date type="Actual">September 30, 2022</completion_date>
  <primary_completion_date type="Actual">September 30, 2022</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>
    <intervention_model_description>Serial monthly vocal fold injections with PRP for total of 4 injections.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events as assessed by FDA/CBER Adverse Event Severity Grading Scale</measure>
    <time_frame>4 months</time_frame>
    <description>Adverse event severity grading scale from 1 to 4, with grade 1 as mild, grade 2 as moderate, grade 3 as severe, and grade 4 potentially life-threatening</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Voice-Related Quality of Life as assessed by Voice Handicap Index-10 (VHI-10) and Vocal Fatigue Index (VFI)</measure>
    <time_frame>4 months</time_frame>
    <description>VHI-10 is a patient questionnaire with 10 statements rated from 0 to 4 with overall scale 0-40; VFI is a patient questionnaire with 19 statements rated from 0-4 with overall scale 0-76.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Vocal Quality as assessed by experts using the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) instrument</measure>
    <time_frame>4 months</time_frame>
    <description>Blinded evaluations of audio voice recordings will be performed by laryngologists and speech-language pathologists using the CAPE-V, which grades overall severity, roughness, breathiness, strain, pitch, and loudness from 0-100.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vocal Fold Appearance as assessed by experts using a modified version of the Voice-Vibratory Assessment with Laryngeal Imaging (VALI) form</measure>
    <time_frame>4 months</time_frame>
    <description>Blinded assessments of recorded laryngeal videostroboscopy exams will be performed by laryngologists and speech-language pathologists using a modified version of the VALI, which is a graphical rating form to grade various components seen on stroboscopy.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Presbylarynx</condition>
  <condition>Atrophy; Larynx</condition>
  <condition>Dysphonia</condition>
  <condition>Vocal Cord Atrophy</condition>
  <condition>Presbylarynges</condition>
  <condition>Vocal Fold Scar</condition>
  <condition>Sulcus Vocalis of Vocal Cord</condition>
  <arm_group>
    <arm_group_label>Serial PRP injections</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This arm will receive experimental intervention of serial monthly platelet-rich plasma (PRP) injections to a unilateral vocal fold mucosa for a total of 4 injections.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Serial PRP injections</intervention_name>
    <description>Autologous platelet-rich plasma will be injected into the vocal fold mucosa in a serial fashion, once per month for a total of 4 injections.</description>
    <arm_group_label>Serial PRP injections</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Vocal fold atrophy, scar, and/or sulcus vocalis diagnosed on laryngeal video&#xD;
             stroboscopy by a fellowship-trained laryngologist&#xD;
&#xD;
          -  Patients with a pre-injection VHI-10 score of ≥ 10&#xD;
&#xD;
          -  Willingness to follow study requirements and perform follow-up visits for up to 4&#xD;
             months following the procedure&#xD;
&#xD;
          -  Ability to give informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Other co-existing laryngeal pathology that would affect either the safety or potential&#xD;
             benefit from PRP injection&#xD;
&#xD;
          -  Current smoker&#xD;
&#xD;
          -  Underlying coagulopathy, thrombocytopenia, or platelet dysfunction&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Johns, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Southern California</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Southern California</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Bradley JP, Hapner E, Johns MM 3rd. What is the optimal treatment for presbyphonia? Laryngoscope. 2014 Nov;124(11):2439-40. doi: 10.1002/lary.24642. Epub 2014 Aug 5. No abstract available.</citation>
    <PMID>25132245</PMID>
  </reference>
  <reference>
    <citation>Crawley BK, Dehom S, Thiel C, Yang J, Cragoe A, Mousselli I, Krishna P, Murry T. Assessment of Clinical and Social Characteristics That Distinguish Presbylaryngis From Pathologic Presbyphonia in Elderly Individuals. JAMA Otolaryngol Head Neck Surg. 2018 Jul 1;144(7):566-571. doi: 10.1001/jamaoto.2018.0409.</citation>
    <PMID>29799925</PMID>
  </reference>
  <reference>
    <citation>Cobden SB, Ozturk K, Duman S, Esen H, Aktan TM, Avunduk MC, Elsurer C. Treatment of Acute Vocal Fold Injury With Platelet-Rich Plasma. J Voice. 2016 Nov;30(6):731-735. doi: 10.1016/j.jvoice.2015.07.012. Epub 2015 Aug 17.</citation>
    <PMID>26292799</PMID>
  </reference>
  <reference>
    <citation>Woo SH, Jeong HS, Kim JP, Koh EH, Lee SU, Jin SM, Kim DH, Sohn JH, Lee SH. Favorable vocal fold wound healing induced by platelet-rich plasma injection. Clin Exp Otorhinolaryngol. 2014 Mar;7(1):47-52. doi: 10.3342/ceo.2014.7.1.47. Epub 2014 Feb 5.</citation>
    <PMID>24587881</PMID>
  </reference>
  <reference>
    <citation>Ozgursoy SK, Tunckasik F, Tunckasik ME, Akincioglu E, Dogan H, Beriat GK. Histopathologic Evaluation of Hyaluronic Acid and Plasma-Rich Platelet Injection into Rabbit Vocal Cords: An Experimental Study. Turk Arch Otorhinolaryngol. 2018 Mar;56(1):30-35. doi: 10.5152/tao.2018.2942. Epub 2018 Mar 1.</citation>
    <PMID>29988271</PMID>
  </reference>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>September 29, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 21, 2018</study_first_posted>
  <last_update_submitted>May 8, 2023</last_update_submitted>
  <last_update_submitted_qc>May 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Southern California</investigator_affiliation>
    <investigator_full_name>Michael Johns</investigator_full_name>
    <investigator_title>Professor, Otolaryngology-Head and Neck Surgery; Director, USC Voice Center</investigator_title>
  </responsible_party>
  <keyword>presbyphonia</keyword>
  <keyword>presbylarynx</keyword>
  <keyword>vocal fold atrophy</keyword>
  <keyword>dysphonia</keyword>
  <keyword>platelet rich plasma</keyword>
  <keyword>PRP</keyword>
  <keyword>vocal fold scar</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dysphonia</mesh_term>
    <mesh_term>Hoarseness</mesh_term>
    <mesh_term>Atrophy</mesh_term>
  </condition_browse>
  <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/NCT03749863
org study id: APP-18-05224
nct id: NCT03749863
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will investigate the safety and efficacy of four serial monthly vocal fold
      injections of platelet-rich plasma to treat dysphonia secondary to vocal fold atrophy, scar,
      and/or sulcus vocalis with glottal insufficiency
Vocal fold atrophy, scar, sulcus vocalis, glottal insufficiency with resulting dysphonia is a
      condition affecting millions of aging Americans, up to 35% of those 65 or older. Currently
      used treatment methods include voice therapy, injections of inert fillers, and laryngeal
      framework surgery. These modalities are imperfect with voice therapy requiring considerable
      time commitment, filler injections generally temporary in benefit, and surgery with increased
      risks. The investigators intend to conduct a single-arm study to assess the safety and
      efficacy of autologous platelet-rich plasma (PRP) injection for vocal fold atrophy, sulcus
      vocalis and scar. PRP is a substance purified from the patient's own blood that consists of
      platelets, growth factors, and other regenerative molecules that have been shown to promote
      rejuvenation in a variety of tissue types. Patients with vocal fold atrophy, sulcus vocalis,
      and scar identified in the USC Voice Center will be offered participation in a study to
      receive serial PRP injections in one vocal fold. Outcome measures evaluated pre- and
      post-injection and over follow-up visits will include various patient reported quality of
      life indices, objective clinical assessments of voice, and laryngeal videostroboscopy
      examinations. The investigators hypothesize that serial PRP injections will significantly
      improve vocal fold mucosal volume, morphology, and dysphonia in these patients with no
      adverse side effects.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Serial monthly vocal fold injections with PRP for total of 4 injections.
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Treatment-Emergent Adverse Events as assessed by FDA/CBER Adverse Event Severity Grading Scale
time frame: 4 months
description: Adverse event severity grading scale from 1 to 4, with grade 1 as mild, grade 2 as moderate, grade 3 as severe, and grade 4 potentially life-threatening
measure: Voice-Related Quality of Life as assessed by Voice Handicap Index-10 (VHI-10) and Vocal Fatigue Index (VFI)
time frame: 4 months
description: VHI-10 is a patient questionnaire with 10 statements rated from 0 to 4 with overall scale 0-40; VFI is a patient questionnaire with 19 statements rated from 0-4 with overall scale 0-76.
measure: Objective Vocal Quality as assessed by experts using the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) instrument
time frame: 4 months
description: Blinded evaluations of audio voice recordings will be performed by laryngologists and speech-language pathologists using the CAPE-V, which grades overall severity, roughness, breathiness, strain, pitch, and loudness from 0-100.
measure: Vocal Fold Appearance as assessed by experts using a modified version of the Voice-Vibratory Assessment with Laryngeal Imaging (VALI) form
time frame: 4 months
description: Blinded assessments of recorded laryngeal videostroboscopy exams will be performed by laryngologists and speech-language pathologists using a modified version of the VALI, which is a graphical rating form to grade various components seen on stroboscopy.
arm group label: Serial PRP injections
arm group type: Experimental
description: This arm will receive experimental intervention of serial monthly platelet-rich plasma (PRP) injections to a unilateral vocal fold mucosa for a total of 4 injections.
intervention type: Procedure
intervention name: Serial PRP injections
description: Autologous platelet-rich plasma will be injected into the vocal fold mucosa in a serial fashion, once per month for a total of 4 injections.
arm group label: Serial PRP injections
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael Johns, MD
role: Principal Investigator
affiliation: University of Southern California
facility: 
country: United States
citation: Bradley JP, Hapner E, Johns MM 3rd. What is the optimal treatment for presbyphonia? Laryngoscope. 2014 Nov;124(11):2439-40. doi: 10.1002/lary.24642. Epub 2014 Aug 5. No abstract available.
PMID: 25132245
citation: Crawley BK, Dehom S, Thiel C, Yang J, Cragoe A, Mousselli I, Krishna P, Murry T. Assessment of Clinical and Social Characteristics That Distinguish Presbylaryngis From Pathologic Presbyphonia in Elderly Individuals. JAMA Otolaryngol Head Neck Surg. 2018 Jul 1;144(7):566-571. doi: 10.1001/jamaoto.2018.0409.
PMID: 29799925
citation: Cobden SB, Ozturk K, Duman S, Esen H, Aktan TM, Avunduk MC, Elsurer C. Treatment of Acute Vocal Fold Injury With Platelet-Rich Plasma. J Voice. 2016 Nov;30(6):731-735. doi: 10.1016/j.jvoice.2015.07.012. Epub 2015 Aug 17.
PMID: 26292799
citation: Woo SH, Jeong HS, Kim JP, Koh EH, Lee SU, Jin SM, Kim DH, Sohn JH, Lee SH. Favorable vocal fold wound healing induced by platelet-rich plasma injection. Clin Exp Otorhinolaryngol. 2014 Mar;7(1):47-52. doi: 10.3342/ceo.2014.7.1.47. Epub 2014 Feb 5.
PMID: 24587881
citation: Ozgursoy SK, Tunckasik F, Tunckasik ME, Akincioglu E, Dogan H, Beriat GK. Histopathologic Evaluation of Hyaluronic Acid and Plasma-Rich Platelet Injection into Rabbit Vocal Cords: An Experimental Study. Turk Arch Otorhinolaryngol. 2018 Mar;56(1):30-35. doi: 10.5152/tao.2018.2942. Epub 2018 Mar 1.
PMID: 29988271
responsible party type: Principal Investigator
investigator affiliation: University of Southern California
investigator full name: Michael Johns
investigator title: Professor, Otolaryngology-Head and Neck Surgery; Director, USC Voice Center
mesh term: Dysphonia
mesh term: Hoarseness
mesh term: Atrophy
sharing ipd: No