<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/NCT04424394</url>
  </required_header>
  <id_info>
    <org_study_id>BIOINT - 2020DSWJ/ED</org_study_id>
    <nct_id>NCT04424394</nct_id>
  </id_info>
  <brief_title>DualStim Therapy With or Without Umbilical Cord Derived Wharton's Jelly for Erectile Dysfunction</brief_title>
  <official_title>A Pilot Study to Evaluate the Immediate and Short-term Efficacy of DualStim (Focused and Radial Extracorporeal Shock Wave) Therapy With and Without Intracavernosal Wharton's Jelly in Patients With Erectile Dysfunction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>BioIntegrate</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>BioIntegrate</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the immediate and short-term efficacy of the&#xD;
      methodological application of DualStim Therapy - Focused Extracorporeal Shock Wave Therapy&#xD;
      (fESWT) and Radial Extracorporeal Shock Wave Therapy (rESWT), with and without&#xD;
      intracavernosal administration of formulated umbilical cord derived Wharton's Jelly to&#xD;
      improve and/or restore erectile function in patients with erectile dysfunction (ED).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Erectile Dysfunction (ED) is broadly defined as the inability to achieve or maintain an&#xD;
      erection sufficient for sexual intercourse or activity. Current treatment for ED consists of&#xD;
      oral medications, vacuum devices, intracavernosal injections, and surgically placed penile&#xD;
      prosthetics. In the literature, this has been described as a Stepwise Approach, offering&#xD;
      therapy beginning with the least invasive treatment option.&#xD;
&#xD;
      The low intensity extracorporeal shock wave therapy (LISWT) was recently approved by the FDA&#xD;
      for treatment of diabetic ulcers. But it is still under evaluation for treatment of ED.&#xD;
      Recently, the European Association of Urology updated their guidelines related to ED and&#xD;
      included LISWT for men with mild to moderate ED. Studies have reported that LISWT can be&#xD;
      effective in treating ED. This was attributed to increase in angiogenesis, neurogenesis and&#xD;
      other rejuvenating tissue effects. Doppler ultrasound studies have demonstrated a sustained&#xD;
      increase in blood flow in patients treated with LISWT. Published studies have also reported a&#xD;
      response rate of 40-80% with this treatment. In addition, the energy/pulse used in this&#xD;
      application is approximately 10% of the energy used for disintegrating kidney stones; and no&#xD;
      serious side effects have been reported till date.&#xD;
&#xD;
      Additionally, most completed studies included men who score in the moderate to minimal ranges&#xD;
      on the International Index of Erectile Function. In the proposed study, men with severe to&#xD;
      moderate ED based on IIEF-EF score will be included. The goal of this study is to improve&#xD;
      and/or restore erectile function in men with erectile dysfunction. The investigators&#xD;
      hypothesize (Alternate Hypothesis) that patients in the active treatment group (DualStim +&#xD;
      Wharton's Jelly) will show an improvement of at least 4 points for moderate ED and at least 7&#xD;
      points for severe ED on IIEF-EF scale/questionnaire, and this difference will be&#xD;
      significantly different from their baseline. In addition, patients in the DualStim + Saline&#xD;
      group will be significantly different from their baseline, however, will show less&#xD;
      improvement compared to DualStim + Wharton's Jelly. Our null hypothesis is that there is no&#xD;
      difference between DualStim with Saline and DualStim with Wharton's Jelly groups and no&#xD;
      difference between the baseline and after-treatment within the treatment groups for&#xD;
      alleviating ED measured using International Index of Erectile Function score (IIEF-EF).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">January 1, 2023</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse or Severe adverse events associated with Intracavernosal administration of umbilical cord derived Wharton's Jelly injection.</measure>
    <time_frame>During the procedure</time_frame>
    <description>To determine the safety i.e. adverse or severe adverse events associated with intracavernosal administration of umbilical cord derived Wharton's Jelly injection. Any adverse or severe adverse events will be recorded in the associated case report forms.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse or Severe adverse events associated with Intracavernosal administration of umbilical cord derived Wharton's Jelly injection.</measure>
    <time_frame>1 month follow-up visit</time_frame>
    <description>To determine the safety i.e. adverse or severe adverse events associated with intracavernosal administration of umbilical cord derived Wharton's Jelly injection. Any adverse or severe adverse events will be recorded in the associated case report forms.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse or Severe adverse events associated with Intracavernosal administration of umbilical cord derived Wharton's Jelly injection.</measure>
    <time_frame>3 month follow-up visit</time_frame>
    <description>To determine the safety i.e. adverse or severe adverse events associated with intracavernosal administration of umbilical cord derived Wharton's Jelly injection. Any adverse or severe adverse events will be recorded in the associated case report forms.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse or Severe adverse events associated with Intracavernosal administration of umbilical cord derived Wharton's Jelly injection.</measure>
    <time_frame>6 month follow-up visit</time_frame>
    <description>To determine the safety i.e. adverse or severe adverse events associated with intracavernosal administration of umbilical cord derived Wharton's Jelly injection. Any adverse or severe adverse events will be recorded in the associated case report forms.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse or Severe adverse events associated with Intracavernosal administration of umbilical cord derived Wharton's Jelly injection.</measure>
    <time_frame>12 month follow-up visit</time_frame>
    <description>To determine the safety i.e. adverse or severe adverse events associated with intracavernosal administration of umbilical cord derived Wharton's Jelly injection. Any adverse or severe adverse events will be recorded in the associated case report forms.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse or Severe adverse events associated with Intracavernosal administration of umbilical cord derived Wharton's Jelly injection.</measure>
    <time_frame>18 month follow-up visit</time_frame>
    <description>To determine the safety i.e. adverse or severe adverse events associated with intracavernosal administration of umbilical cord derived Wharton's Jelly injection. Any adverse or severe adverse events will be recorded in the associated case report forms.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Immediate and short-term efficacy of DualStim Therapy with Wharton's Jelly based on changes in the International Index of Erectile Function Questionnaire score compared to baseline</measure>
    <time_frame>through study completion, an average of 18 months</time_frame>
    <description>To evaluate the immediate and short-term efficacy of DualStim Therapy with Wharton's Jelly based on changes in the International Index of Erectile Function Questionnaire score compared to baseline score. An increase in the score indicates improvement.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Immediate and short-term efficacy of DualStim Therapy with Wharton's Jelly compared to DualStim Therapy with saline based on changes in the International Index of Erectile Function Questionnaire score.</measure>
    <time_frame>through study completion, an average of 18 months</time_frame>
    <description>To evaluate the immediate and short-term efficacy of DualStim Therapy with Wharton's Jelly compared to DualStim Therapy with saline based on changes in the International Index of Erectile Function Questionnaire score at each time-point.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sexual activity improvement according to Sexual Encounter Profile Questionnaire from baseline leading to optimal penetration at follow-ups</measure>
    <time_frame>through study completion, an average of 18 months</time_frame>
    <description>To study sexual activity improvement from baseline leading to optimal penetration at follow-ups 1, 3 and 6 months' post treatment according to Sexual Encounter Profile Questionnaire. An increase in score indicates improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sexual activity improvement according to Global Assessment Questionnaire from baseline leading to optimal penetration at follow-ups</measure>
    <time_frame>through study completion, an average of 18 months</time_frame>
    <description>To study sexual activity improvement from baseline leading to optimal penetration at follow-ups 1, 3 and 6 months' post treatment according to Global Assessment Questionnaire. An increase in score indicates improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sexual activity improvement according to Erection Hardness Score from baseline leading to optimal penetration at follow-ups</measure>
    <time_frame>through study completion, an average of 18 months</time_frame>
    <description>To study sexual activity improvement from baseline leading to optimal penetration at follow-ups 1, 3 and 6 months' post treatment according to Erection Hardness Score. An increase in score indicates improvement.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Erectile Dysfunction</condition>
  <arm_group>
    <arm_group_label>DualStim Therapy with Wharton's Jelly Injection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>DualStim therapy with intracavernosal injection of umbilical cord-derived Wharton's Jelly formulation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DualStim Therapy without Wharton's Jelly Injection</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>DualStim therapy with intracavernosal injection of normal saline.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>DualStim Therapy</intervention_name>
    <description>6 DualStim Therapies over a period of 7 weeks.</description>
    <arm_group_label>DualStim Therapy with Wharton's Jelly Injection</arm_group_label>
    <arm_group_label>DualStim Therapy without Wharton's Jelly Injection</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Umbilical cord-derived Wharton's Jelly</intervention_name>
    <description>2 intracavernosal injections over a period of 7 weeks.</description>
    <arm_group_label>DualStim Therapy with Wharton's Jelly Injection</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Saline</intervention_name>
    <description>2 intracavernosal injections over a period of 7 weeks.</description>
    <arm_group_label>DualStim Therapy without Wharton's Jelly Injection</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Only Male patients who are 40 to 80 years old (both numbers inclusive).&#xD;
&#xD;
          2. Must have a body mass index (BMI) of less than 35.&#xD;
&#xD;
          3. Patients with ED for at least 1 year but less than 10 years.&#xD;
&#xD;
          4. The patient is poorly phosphodiesterase type 5 inhibitors responsive, meaning he is&#xD;
             able to achieve an erection but is unable or partially able to satisfactory complete&#xD;
             sexual intercourse (penetration and/or orgasm).&#xD;
&#xD;
          5. Minimum IIEF-EF domain score of 11-16 (for classification as moderate ED).&#xD;
&#xD;
          6. IIEF-ED score ≥11 and ≤25 while taking phosphodiesterase type 5 inhibitors or in&#xD;
             injection therapy.&#xD;
&#xD;
          7. Be willing and capable of giving written informed consent to participate in this&#xD;
             clinical study.&#xD;
&#xD;
          8. Be willing and capable of complying with study-related requirements, procedures and&#xD;
             visits.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with history of radical prostatectomy or extensive pelvic surgery.&#xD;
&#xD;
          2. Patients with past radiation therapy of the pelvic region within 12 months prior to&#xD;
             enrollment.&#xD;
&#xD;
          3. Patients recovering from cancer within 12 months prior to enrollment.&#xD;
&#xD;
          4. Patients who are taking blood thinners or have history of Diabetes Mellitus.&#xD;
&#xD;
          5. Patients with untreated hypogonadism or thyroid disease.&#xD;
&#xD;
          6. Patients with deformed Penis on physical exam form.&#xD;
&#xD;
          7. Patients who participated in another clinical trial or treatment with any&#xD;
             investigational product within last 30 days prior to inclusion in the study.&#xD;
&#xD;
          8. Patients with serious neurological, psychological or psychiatric disorders which may&#xD;
             affect erectile function.&#xD;
&#xD;
          9. Patients with other medical conditions determined by site principal investigator as&#xD;
             interfering with the study.&#xD;
&#xD;
         10. Patients with an injury or disability claim under current litigation or pending or&#xD;
             approved workers' compensation claim.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Only Male patients are eligible to participate.</gender_description>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Richard Gaines, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>LifeGAINES Medical and Aesthetics Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ashim Gupta, PhD, MBA</last_name>
    <role>Study Director</role>
    <affiliation>BioIntegrate</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Richard Gaines, MD</last_name>
    <phone>561-931-2430</phone>
    <email>rg3090@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Ashim Gupta, PhD, MBA</last_name>
    <email>agupta@biointegrate.com</email>
  </overall_contact_backup>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>July 20, 2022</last_update_submitted>
  <last_update_submitted_qc>July 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Erectile Dysfunction</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/NCT04424394
org study id: BIOINT - 2020DSWJ/ED
nct id: NCT04424394
lead sponsor: 
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
The purpose of this study is to determine the immediate and short-term efficacy of the
      methodological application of DualStim Therapy - Focused Extracorporeal Shock Wave Therapy
      (fESWT) and Radial Extracorporeal Shock Wave Therapy (rESWT), with and without
      intracavernosal administration of formulated umbilical cord derived Wharton's Jelly to
      improve and/or restore erectile function in patients with erectile dysfunction (ED).
Erectile Dysfunction (ED) is broadly defined as the inability to achieve or maintain an
      erection sufficient for sexual intercourse or activity. Current treatment for ED consists of
      oral medications, vacuum devices, intracavernosal injections, and surgically placed penile
      prosthetics. In the literature, this has been described as a Stepwise Approach, offering
      therapy beginning with the least invasive treatment option.

      The low intensity extracorporeal shock wave therapy (LISWT) was recently approved by the FDA
      for treatment of diabetic ulcers. But it is still under evaluation for treatment of ED.
      Recently, the European Association of Urology updated their guidelines related to ED and
      included LISWT for men with mild to moderate ED. Studies have reported that LISWT can be
      effective in treating ED. This was attributed to increase in angiogenesis, neurogenesis and
      other rejuvenating tissue effects. Doppler ultrasound studies have demonstrated a sustained
      increase in blood flow in patients treated with LISWT. Published studies have also reported a
      response rate of 40-80% with this treatment. In addition, the energy/pulse used in this
      application is approximately 10% of the energy used for disintegrating kidney stones; and no
      serious side effects have been reported till date.

      Additionally, most completed studies included men who score in the moderate to minimal ranges
      on the International Index of Erectile Function. In the proposed study, men with severe to
      moderate ED based on IIEF-EF score will be included. The goal of this study is to improve
      and/or restore erectile function in men with erectile dysfunction. The investigators
      hypothesize (Alternate Hypothesis) that patients in the active treatment group (DualStim +
      Wharton's Jelly) will show an improvement of at least 4 points for moderate ED and at least 7
      points for severe ED on IIEF-EF scale/questionnaire, and this difference will be
      significantly different from their baseline. In addition, patients in the DualStim + Saline
      group will be significantly different from their baseline, however, will show less
      improvement compared to DualStim + Wharton's Jelly. Our null hypothesis is that there is no
      difference between DualStim with Saline and DualStim with Wharton's Jelly groups and no
      difference between the baseline and after-treatment within the treatment groups for
      alleviating ED measured using International Index of Erectile Function score (IIEF-EF).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Adverse or Severe adverse events associated with Intracavernosal administration of umbilical cord derived Wharton's Jelly injection.
time frame: During the procedure
description: To determine the safety i.e. adverse or severe adverse events associated with intracavernosal administration of umbilical cord derived Wharton's Jelly injection. Any adverse or severe adverse events will be recorded in the associated case report forms.
measure: Adverse or Severe adverse events associated with Intracavernosal administration of umbilical cord derived Wharton's Jelly injection.
time frame: 1 month follow-up visit
description: To determine the safety i.e. adverse or severe adverse events associated with intracavernosal administration of umbilical cord derived Wharton's Jelly injection. Any adverse or severe adverse events will be recorded in the associated case report forms.
measure: Adverse or Severe adverse events associated with Intracavernosal administration of umbilical cord derived Wharton's Jelly injection.
time frame: 3 month follow-up visit
description: To determine the safety i.e. adverse or severe adverse events associated with intracavernosal administration of umbilical cord derived Wharton's Jelly injection. Any adverse or severe adverse events will be recorded in the associated case report forms.
measure: Adverse or Severe adverse events associated with Intracavernosal administration of umbilical cord derived Wharton's Jelly injection.
time frame: 6 month follow-up visit
description: To determine the safety i.e. adverse or severe adverse events associated with intracavernosal administration of umbilical cord derived Wharton's Jelly injection. Any adverse or severe adverse events will be recorded in the associated case report forms.
measure: Adverse or Severe adverse events associated with Intracavernosal administration of umbilical cord derived Wharton's Jelly injection.
time frame: 12 month follow-up visit
description: To determine the safety i.e. adverse or severe adverse events associated with intracavernosal administration of umbilical cord derived Wharton's Jelly injection. Any adverse or severe adverse events will be recorded in the associated case report forms.
measure: Adverse or Severe adverse events associated with Intracavernosal administration of umbilical cord derived Wharton's Jelly injection.
time frame: 18 month follow-up visit
description: To determine the safety i.e. adverse or severe adverse events associated with intracavernosal administration of umbilical cord derived Wharton's Jelly injection. Any adverse or severe adverse events will be recorded in the associated case report forms.
measure: Immediate and short-term efficacy of DualStim Therapy with Wharton's Jelly based on changes in the International Index of Erectile Function Questionnaire score compared to baseline
time frame: through study completion, an average of 18 months
description: To evaluate the immediate and short-term efficacy of DualStim Therapy with Wharton's Jelly based on changes in the International Index of Erectile Function Questionnaire score compared to baseline score. An increase in the score indicates improvement.
measure: Immediate and short-term efficacy of DualStim Therapy with Wharton's Jelly compared to DualStim Therapy with saline based on changes in the International Index of Erectile Function Questionnaire score.
time frame: through study completion, an average of 18 months
description: To evaluate the immediate and short-term efficacy of DualStim Therapy with Wharton's Jelly compared to DualStim Therapy with saline based on changes in the International Index of Erectile Function Questionnaire score at each time-point.
measure: Sexual activity improvement according to Sexual Encounter Profile Questionnaire from baseline leading to optimal penetration at follow-ups
time frame: through study completion, an average of 18 months
description: To study sexual activity improvement from baseline leading to optimal penetration at follow-ups 1, 3 and 6 months' post treatment according to Sexual Encounter Profile Questionnaire. An increase in score indicates improvement.
measure: Sexual activity improvement according to Global Assessment Questionnaire from baseline leading to optimal penetration at follow-ups
time frame: through study completion, an average of 18 months
description: To study sexual activity improvement from baseline leading to optimal penetration at follow-ups 1, 3 and 6 months' post treatment according to Global Assessment Questionnaire. An increase in score indicates improvement.
measure: Sexual activity improvement according to Erection Hardness Score from baseline leading to optimal penetration at follow-ups
time frame: through study completion, an average of 18 months
description: To study sexual activity improvement from baseline leading to optimal penetration at follow-ups 1, 3 and 6 months' post treatment according to Erection Hardness Score. An increase in score indicates improvement.
arm group label: DualStim Therapy with Wharton's Jelly Injection
arm group type: Experimental
description: DualStim therapy with intracavernosal injection of umbilical cord-derived Wharton's Jelly formulation.
arm group label: DualStim Therapy without Wharton's Jelly Injection
arm group type: Active Comparator
description: DualStim therapy with intracavernosal injection of normal saline.
intervention type: Device
intervention name: DualStim Therapy
description: 6 DualStim Therapies over a period of 7 weeks.
arm group label: DualStim Therapy with Wharton's Jelly Injection
arm group label: DualStim Therapy without Wharton's Jelly Injection
intervention type: Biological
intervention name: Umbilical cord-derived Wharton's Jelly
description: 2 intracavernosal injections over a period of 7 weeks.
arm group label: DualStim Therapy with Wharton's Jelly Injection
intervention type: Other
intervention name: Saline
description: 2 intracavernosal injections over a period of 7 weeks.
arm group label: DualStim Therapy without Wharton's Jelly Injection
criteria: 
gender: Male
gender based: Yes
gender description: Only Male patients are eligible to participate.
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
last name: Richard Gaines, MD
role: Principal Investigator
affiliation: LifeGAINES Medical and Aesthetics Center
last name: Ashim Gupta, PhD, MBA
role: Study Director
affiliation: BioIntegrate
last name: Richard Gaines, MD
phone: 561-931-2430
email: rg3090@gmail.com
last name: Ashim Gupta, PhD, MBA
email: agupta@biointegrate.com
responsible party type: Sponsor
mesh term: Erectile Dysfunction
sharing ipd: No