<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/NCT01708525</url>
  </required_header>
  <id_info>
    <org_study_id>ULT-132</org_study_id>
    <nct_id>NCT01708525</nct_id>
  </id_info>
  <brief_title>Feasibility Study: Heavy Water Tissue Labeling Protocol</brief_title>
  <official_title>Feasibility Study: Determination of the Effect of Ultherapy® Treatment on the Rate of Collagen Synthesis in Normal Skin</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ulthera, Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merz North America, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Enrolled subjects undergo tissue labeling to evaluate the rate of collagen synthesis in&#xD;
      tissue treated with the Ulthera® System compared to control tissue.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a prospective, single-center, blinded, non-randomized clinical trial. Two&#xD;
      subjects who have chosen to have a surgical facelift procedure and agree to drink heavy water&#xD;
      for tissue labeling, will be enrolled. Subjects will consume heavy water and collect saliva&#xD;
      specimens over the course of the study period, following a specific heavy water labeling&#xD;
      protocol. Two weeks after starting the heavy water protocol, subjects will return to the&#xD;
      study site to receive one Ultherapy® treatment to the pre-auricular region on one side of the&#xD;
      face. The contra-lateral pre-auricular region will serve as a control. Following Ultherapy®&#xD;
      treatment, subjects will continue to follow the heavy water protocol for 4 more weeks.&#xD;
      Subjects will then return to the study site to undergo resection of the treated and control&#xD;
      tissue for analysis during their planned rhytidectomy procedure. Subjects will send in saliva&#xD;
      samples on a weekly basis to allow for confirmation that they are drinking the heavy water.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">November 2013</completion_date>
  <primary_completion_date type="Actual">November 2013</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of Collagen Synthesis</measure>
    <time_frame>4 weeks post-treatment</time_frame>
    <description>Resected tissue will be analyzed to determine the rate of collagen synthesis in tissue treated with Ultherapy® compared to non-treated tissue.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">2</enrollment>
  <condition>Skin Laxity</condition>
  <arm_group>
    <arm_group_label>Ultherapy®-treated tissue</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Heavy water labeled tissue receiving an Ulthera® System Treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Ulthera® System Treatment</intervention_name>
    <description>Focused ultrasound energy delivered below the surface of the skin</description>
    <arm_group_label>Ultherapy®-treated tissue</arm_group_label>
    <other_name>Ultherapy®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Heavy Water</intervention_name>
    <description>A tissue labeling model via the consumption of the stable isotope, deuterated water (heavy water). Heavy water consumed over the course of the 6-week study period for a direct kinetic measure of in vivo collagen synthesis. 60 ml (about 12 teaspoons) of heavy water (also called deuterated water or 2H2O), was consumed three times a day for the first five days. Starting on Day 6, two 60 ml doses of heavy water were consumed per day for the remaining 37 days.</description>
    <arm_group_label>Ultherapy®-treated tissue</arm_group_label>
    <other_name>Deuterated Water</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female, age 30 to 65 years scheduled for rhytidectomy.&#xD;
&#xD;
          -  Subject in good health.&#xD;
&#xD;
          -  Understands and accepts the obligation not to undergo any other procedures in the&#xD;
             areas to be treated.&#xD;
&#xD;
          -  Willingness and ability to comply with protocol requirements, including returning for&#xD;
             follow-up visits and abstaining from exclusionary procedures for the duration of the&#xD;
             study.&#xD;
&#xD;
          -  Subjects of childbearing potential must have a negative urine pregnancy test result&#xD;
             and must not be lactating at Visit 1 and be willing and able to use an acceptable&#xD;
             method of birth control.&#xD;
&#xD;
          -  Absence of physical or psychological conditions unacceptable to the investigator.&#xD;
&#xD;
          -  Willingness and ability to provide written consent for study-required photography and&#xD;
             adherence to photography procedures (i.e., removal of jewelry and makeup).&#xD;
&#xD;
          -  Willingness and ability to provide written informed consent and HIPAA authorization&#xD;
             prior to performance of any study-related procedure.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of an active systemic or local skin disease that may affect wound healing.&#xD;
&#xD;
          -  Severe solar elastosis.&#xD;
&#xD;
          -  Significant scarring in areas to be treated.&#xD;
&#xD;
          -  Open wounds or lesions in the area to be treated.&#xD;
&#xD;
          -  Severe or cystic acne on the area to be treated.&#xD;
&#xD;
          -  Presence of a metal stent or implant in the facial area to be treated.&#xD;
&#xD;
          -  Inability to understand the protocol or to give informed consent.&#xD;
&#xD;
          -  Microdermabrasion, or prescription level glycolic acid treatments to the submental&#xD;
             area within two weeks prior to study participation or during the study.&#xD;
&#xD;
          -  Excessive dermatochalasis, deep dermal scarring, or thick sebaceous skin in the area&#xD;
             to be treated.&#xD;
&#xD;
          -  BMI equal to or greater than 30.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gordon Sasaki, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sasaki Advanced Aesthetic Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sasaki Advanced Aesthetic Medical Center</name>
      <address>
        <city>Pasadena</city>
        <state>California</state>
        <zip>91105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>October 15, 2012</study_first_submitted>
  <study_first_submitted_qc>October 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 17, 2012</study_first_posted>
  <results_first_submitted>June 16, 2014</results_first_submitted>
  <results_first_submitted_qc>December 4, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">December 12, 2014</results_first_posted>
  <last_update_submitted>November 10, 2017</last_update_submitted>
  <last_update_submitted_qc>November 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 11, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Ulthera® System</keyword>
  <keyword>Ultherapy® Treatment</keyword>
  <keyword>Ulthera, Inc.</keyword>
  <keyword>Ultrasound treatment for skin tightening</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cutis Laxa</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Deuterium Oxide</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Ultherapy®-Treated Tissue</title>
          <description>Heavy water labeled tissue receiving an Ultherapy® Treatment&#xD;
Ulthera System® Treatment: Focused ultrasound energy delivered below the surface of the skin</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Both study subjects completed two weeks of heavy water tissue labeling then received Ultherapy® treatment to the pre-auricular region on one side of their face. The non-treated pre-auricular region on the contralateral side served as a control. Treated and non-treated tissue was resected at 4 weeks post Ultherapy® for analysis.</population>
      <group_list>
        <group group_id="B1">
          <title>Ultherapy®-Treated Tissue</title>
          <description>Heavy water labeled tissue receiving an Ultherapy® Treatment&#xD;
Ulthera System® Treatment: Focused ultrasound energy delivered below the surface of the skin</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="2"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62" lower_limit="59" upper_limit="65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Rate of Collagen Synthesis</title>
        <description>Resected tissue will be analyzed to determine the rate of collagen synthesis in tissue treated with Ultherapy® compared to non-treated tissue.</description>
        <time_frame>4 weeks post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Untreated Tissue</title>
            <description>Heavy water labeled tissue NOT receiving an Ultherapy® Treatment</description>
          </group>
          <group group_id="O2">
            <title>Ultherapy®-Treated Tissue</title>
            <description>Heavy water labeled tissue receiving an Ultherapy® Treatment&#xD;
Ulthera® System Treatment: Focused ultrasound energy delivered below the surface of the skin</description>
          </group>
        </group_list>
        <measure>
          <title>Rate of Collagen Synthesis</title>
          <description>Resected tissue will be analyzed to determine the rate of collagen synthesis in tissue treated with Ultherapy® compared to non-treated tissue.</description>
          <units>percentage of new collagen synthesized</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subject 1, Type I Collagen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.71"/>
                    <measurement group_id="O2" value="21.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject 1, Type III Collagen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.11"/>
                    <measurement group_id="O2" value="51.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject 2, Type I Collagen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.53"/>
                    <measurement group_id="O2" value="29.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject 2, Type III Collagen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.34"/>
                    <measurement group_id="O2" value="68.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from baseline through tissue resection, i.e., 4 weeks post-Ultherapy® treatment.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Ultherapy®-Treated Tissue</title>
          <description>Heavy water labeled tissue receiving an Ultherapy® Treatment&#xD;
Ulthera System® Treatment: Focused ultrasound energy delivered below the surface of the skin</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>A limitation of this trial includes only a two subject study population due to the extremely high expense of the tissue analyses conducted. High expense precluded further research in a randomized designed trial with a broader patient population.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Public Disclosure Manager</name_or_title>
      <organization>Merz Pharmaceuticals</organization>
      <email>clinicaltrials@merz.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01708525
org study id: ULT-132
nct id: NCT01708525
lead sponsor: 
has dmc: No
Enrolled subjects undergo tissue labeling to evaluate the rate of collagen synthesis in
      tissue treated with the Ulthera® System compared to control tissue.
This study is a prospective, single-center, blinded, non-randomized clinical trial. Two
      subjects who have chosen to have a surgical facelift procedure and agree to drink heavy water
      for tissue labeling, will be enrolled. Subjects will consume heavy water and collect saliva
      specimens over the course of the study period, following a specific heavy water labeling
      protocol. Two weeks after starting the heavy water protocol, subjects will return to the
      study site to receive one Ultherapy® treatment to the pre-auricular region on one side of the
      face. The contra-lateral pre-auricular region will serve as a control. Following Ultherapy®
      treatment, subjects will continue to follow the heavy water protocol for 4 more weeks.
      Subjects will then return to the study site to undergo resection of the treated and control
      tissue for analysis during their planned rhytidectomy procedure. Subjects will send in saliva
      samples on a weekly basis to allow for confirmation that they are drinking the heavy water.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Rate of Collagen Synthesis
time frame: 4 weeks post-treatment
description: Resected tissue will be analyzed to determine the rate of collagen synthesis in tissue treated with Ultherapy® compared to non-treated tissue.
arm group label: Ultherapy®-treated tissue
arm group type: Experimental
description: Heavy water labeled tissue receiving an Ulthera® System Treatment
intervention type: Device
intervention name: Ulthera® System Treatment
description: Focused ultrasound energy delivered below the surface of the skin
arm group label: Ultherapy®-treated tissue
other name: Ultherapy®
intervention type: Other
intervention name: Heavy Water
description: A tissue labeling model via the consumption of the stable isotope, deuterated water (heavy water). Heavy water consumed over the course of the 6-week study period for a direct kinetic measure of in vivo collagen synthesis. 60 ml (about 12 teaspoons) of heavy water (also called deuterated water or 2H2O), was consumed three times a day for the first five days. Starting on Day 6, two 60 ml doses of heavy water were consumed per day for the remaining 37 days.
arm group label: Ultherapy®-treated tissue
other name: Deuterated Water
criteria: 
gender: All
minimum age: 30 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Gordon Sasaki, MD
role: Principal Investigator
affiliation: Sasaki Advanced Aesthetic Medical Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Cutis Laxa
mesh term: Deuterium Oxide
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: A limitation of this trial includes only a two subject study population due to the extremely high expense of the tissue analyses conducted. High expense precluded further research in a randomized designed trial with a broader patient population.
point of contact: 