<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/NCT01673113</url>
  </required_header>
  <id_info>
    <org_study_id>2012-P-001380</org_study_id>
    <nct_id>NCT01673113</nct_id>
  </id_info>
  <brief_title>Characterization of Transient Alterations of Cutaneous Sensory Nerve Function by Cryolipolysis</brief_title>
  <official_title>Characterization of Transient Alterations of Cutaneous Sensory Nerve Function by Cryolipolysis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cryolipolysis with Zeltiq CoolSculpting device is a novel method of non-invasive fat removal.&#xD;
      The technique works by application of cold plates to the skin surface for a single cooling&#xD;
      cycle lasting 60 minutes, after which a cold-induced inflammatory panniculitis leads to&#xD;
      selective loss of fat. There is no histologic evidence of necrotic or inflammatory damage to&#xD;
      skin or nerves, however a single small human study has reported prolonged temporary altered&#xD;
      sensation (hypoesthesia) in the area of cryolipolysis procedure. This hypoesthesia seen in&#xD;
      about 2/3 of patients, is completely reversible, lasts up to 8 weeks after treatment, and&#xD;
      suggests that cooling under these conditions can temporarily alter sensory nerve function.&#xD;
&#xD;
      The purpose of this study is to further characterize the reversible cutaneous sensory&#xD;
      function alteration after cryolipolysis with Zeltiq CoolSculpting device. Using multiple&#xD;
      modalities of sensory nerve function we hope to elucidate the details of cryolipolysis&#xD;
      induced sensory nerve alteration.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study design We undertook an open-label, prospective study at the Massachusetts General&#xD;
      Hospital (MGH) (Boston, USA) between December 2012 and July 2013. The study was approved by&#xD;
      the MGH Institutional Research Board and was registered at ClinicalTrials.gov (NCT01673113).&#xD;
      Written, informed consent was obtained from all participants prior to participation in the&#xD;
      study. The study conformed to the standards set by the Declaration of Helsinki and Good&#xD;
      Clinical Practice Guidelines.&#xD;
&#xD;
      Eleven healthy subjects were enrolled in the study. They were randomized to have either the&#xD;
      left or right flank treated with a single cycle of cryolipolysis. Baseline measurement of&#xD;
      sensory function was evaluated using QST at the treated and control (untreated) flank for&#xD;
      each subject. Histamine iontophoresis was used to evaluate itch duration and intensity on the&#xD;
      treated and control flank for each subject. All sensory function testing, including responses&#xD;
      to histamine-induced itch, were assessed at 48-72 hours, and Day 7, 14, 21, 35 and 56&#xD;
      post-treatment. In 6 subjects, skin biopsies (3 mm diameter) for histological analysis of&#xD;
      nerve fiber density at the treated flank were taken at baseline, 48-72 hours, Day 21 and 56&#xD;
      post-treatment.&#xD;
&#xD;
      Cryolipolysis procedure All subjects received cryolipolysis treatment to the flank above the&#xD;
      iliac crest, on one side of the body. The untreated (contralateral) flank served as the&#xD;
      control throughout the study. Subjects were randomized to have right or left flank treated&#xD;
      and randomization was achieved with a computer-generated randomization code. The treatment&#xD;
      site was identified, assessed and marked by a single, unblinded investigator. The sensory&#xD;
      testing site within the flanks was marked and registered using a transparent plastic sheet,&#xD;
      aligned using cutaneous landmarks including nevi or scars, and photographed with the subject&#xD;
      in a standard position, to ensure that the same area was tested on follow-up visits.&#xD;
&#xD;
      Cryolipolysis was performed using an EzApp6.3 applicator (CoolScultping, Zeltiq Aesthetics&#xD;
      Inc, Pleasanton USA) and standard settings at cooling intensity factor (CIF) of 41.6,&#xD;
      corresponding to heat transfer of -73mW/cm2, applied for one hour.&#xD;
&#xD;
      Quantitative sensory testing (QST) The QST protocol consisted of a series of 7 sensory tests.&#xD;
      The QST procedure started with the evaluation of mechanical followed by thermal thresholds.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">August 2015</completion_date>
  <primary_completion_date type="Actual">August 2014</primary_completion_date>
  <phase>N/A</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Vibration Detection Threshold (VDT)</measure>
    <time_frame>within 48-72 hours after treatment</time_frame>
    <description>VDT was evaluated using a computerized vibrometer with 1cm2 contact probe placed perpendicularly on the skin (TSA-II, Medoc Inc., Ramat Yishai, Israel). This device gradually increased the vibration magnitude until the subject pressed a &quot;stop&quot; button to indicate when they first felt the vibration. This test was repeated 8 times. The values presented in the data table were averaged over all repeats.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mechanical Detection Threshold (MDT)</measure>
    <time_frame>48-72 hours post treatment</time_frame>
    <description>MDT was evaluated using von Frey Filaments. The up-down method, which evaluates the threshold force for appearance and disappearance of a touch sensation reported by the subject, was used until 3 values were obtained. The values presented in the data table were averaged over all repeats.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Adiposity</condition>
  <arm_group>
    <arm_group_label>Cryolipolysis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects were randomized to have either the left of right flank treated with single the Zeltiq CoolSculpting Device, which is an FDA approved cooling device used for non-invasive and selective reduction of fat around the flanks. Sensory testing was done before and after the procedure.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>All subjects were randomized to have either the left of right flank treated with single the Zeltiq CoolSculpting Device. The untreated flank served as the internal control for each subject.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Zeltiq CoolSculpting device</intervention_name>
    <description>This is an FDA approved cooling device used for non-invasive and selective reduction of fat around the flanks, an area commonly referred to as the &quot;love handles.&quot;</description>
    <arm_group_label>Cryolipolysis</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects ages 18-65 years old, male or female with visible adiposity on the flanks&#xD;
             (love handles) and no weight changes exceeding 10lb during the preceding month.&#xD;
&#xD;
          -  Willingness to participate in the study&#xD;
&#xD;
          -  Informed consent agreement signed by the subject&#xD;
&#xD;
          -  Willingness to follow the treatment schedule and post treatment care requirements&#xD;
&#xD;
          -  Willingness to have skin biopsy done&#xD;
&#xD;
          -  No history of allergy to lidocaine or any other anesthetics.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject has a history of nerve problems, neuropathy&#xD;
&#xD;
          -  Subject who has recently undergone liposuction or another weight loss procedure, had a&#xD;
             history of subcutaneous injections into the area of intended treatment within the&#xD;
             preceding 6 months.&#xD;
&#xD;
          -  Subjects with history of diabetes&#xD;
&#xD;
          -  Subjects with a BMI of 30 or greater&#xD;
&#xD;
          -  Subject has an infection, surgical scars or other dermatologic condition in the area&#xD;
             to be treated&#xD;
&#xD;
          -  Subject has known cold sensitivity disorders including Raynaud's phenomena, cold&#xD;
             urticaria, cryoglobulinemia, or cold induced hemoglobinuria&#xD;
&#xD;
          -  Women who are pregnant or intending to become pregnant in the following 9 months;&#xD;
             women who are lactating or had been lactating in the prior 9 months.&#xD;
&#xD;
          -  Subject is immunosuppressed&#xD;
&#xD;
          -  Subject is unable to comply with treatment, home care or follow-up visits&#xD;
&#xD;
          -  Subject has a history of vitiligo&#xD;
&#xD;
          -  Subject has a history of keloid formation&#xD;
&#xD;
          -  Subject is currently enrolled in a clinical study of any other unapproved&#xD;
             investigational drug or device.&#xD;
&#xD;
          -  Any other condition or laboratory value that would, in the professional opinion of the&#xD;
             investigator, potentially affect the subject's response or the integrity of the data&#xD;
             or would pose an unacceptable risk to the subject.&#xD;
&#xD;
          -  Subject taking anticoagulants&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>R. Rox Anderson, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Wellman Center for Photomedicine, MGH</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.ncbi.nlm.nih.gov/pubmed/26099028</url>
    <description>the published paper</description>
  </link>
  <results_reference>
    <citation>Garibyan L, Cornelissen L, Sipprell W, Pruessner J, Elmariah S, Luo T, Lerner EA, Jung Y, Evans C, Zurakowski D, Berde CB, Rox Anderson R. Transient Alterations of Cutaneous Sensory Nerve Function by Noninvasive Cryolipolysis. J Invest Dermatol. 2015 Nov;135(11):2623-2631. doi: 10.1038/jid.2015.233. Epub 2015 Jun 22.</citation>
    <PMID>26099028</PMID>
  </results_reference>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>August 22, 2012</study_first_submitted>
  <study_first_submitted_qc>August 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 27, 2012</study_first_posted>
  <results_first_submitted>November 5, 2014</results_first_submitted>
  <results_first_submitted_qc>April 7, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">April 10, 2017</results_first_posted>
  <last_update_submitted>September 17, 2019</last_update_submitted>
  <last_update_submitted_qc>September 17, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 1, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Richard Rox Anderson, MD</investigator_full_name>
    <investigator_title>Professor, Harvard Medical School</investigator_title>
  </responsible_party>
  <keyword>cryolipolysis, sensory nerve function, Zeltiq</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obesity</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>11 subjects were randomized to have either left or right flank treated. The untreated flank served as the internal control for each subject.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Treatment</title>
          <description>Subjects were randomized to have either left or right flank treated with cryolipolysis.</description>
        </group>
        <group group_id="P2">
          <title>Control</title>
          <description>The untreated flank of each subject served as internal control.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>BMI of &lt;30 kg/m^2</population>
      <group_list>
        <group group_id="B1">
          <title>Treatment</title>
          <description>Subjects were randomized to have right or left flank treated with Zeltiq CoolSculpting device</description>
        </group>
        <group group_id="B2">
          <title>Control</title>
          <description>The untreated flank of each subject served as the internal control.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="11"/>
            <count group_id="B2" value="11"/>
            <count group_id="B3" value="11"/>
          </count_list>
        </analyzed>
        <analyzed>
          <units>flanks</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="11"/>
            <count group_id="B2" value="11"/>
            <count group_id="B3" value="22"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>flanks</units>
          <param>Count of Units</param>
          <units_analyzed>flanks</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>flanks</units>
          <param>Count of Units</param>
          <units_analyzed>flanks</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>flanks</units>
          <param>Number</param>
          <units_analyzed>flanks</units_analyzed>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI of &lt;30</title>
          <units>flanks</units>
          <param>Count of Units</param>
          <units_analyzed>flanks</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Vibration Detection Threshold (VDT)</title>
        <description>VDT was evaluated using a computerized vibrometer with 1cm2 contact probe placed perpendicularly on the skin (TSA-II, Medoc Inc., Ramat Yishai, Israel). This device gradually increased the vibration magnitude until the subject pressed a &quot;stop&quot; button to indicate when they first felt the vibration. This test was repeated 8 times. The values presented in the data table were averaged over all repeats.</description>
        <time_frame>within 48-72 hours after treatment</time_frame>
        <population>11 subjects were randomized to have right or left flank treated with cryolipolysis. The untreated flank served as the internal control.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment</title>
            <description>Cryolipolysis treated flanks had vibration sensory testing done within 48-72 hours after treatment.</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Untreated flanks of each subject had vibration sensory testing done within 48-72 hours after treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Vibration Detection Threshold (VDT)</title>
          <description>VDT was evaluated using a computerized vibrometer with 1cm2 contact probe placed perpendicularly on the skin (TSA-II, Medoc Inc., Ramat Yishai, Israel). This device gradually increased the vibration magnitude until the subject pressed a &quot;stop&quot; button to indicate when they first felt the vibration. This test was repeated 8 times. The values presented in the data table were averaged over all repeats.</description>
          <population>11 subjects were randomized to have right or left flank treated with cryolipolysis. The untreated flank served as the internal control.</population>
          <units>(um/sec)</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <units_analyzed>flanks</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>flanks</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.3" lower_limit="20.9" upper_limit="31.7"/>
                    <measurement group_id="O2" value="19" lower_limit="13.6" upper_limit="24.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mechanical Detection Threshold (MDT)</title>
        <description>MDT was evaluated using von Frey Filaments. The up-down method, which evaluates the threshold force for appearance and disappearance of a touch sensation reported by the subject, was used until 3 values were obtained. The values presented in the data table were averaged over all repeats.</description>
        <time_frame>48-72 hours post treatment</time_frame>
        <population>11 subjects were randomized to have right or left flank treated with cryolipolysis and the untreated flank served as internal control.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment</title>
            <description>Subjects were randomized to have right or left flank treated with Zeltiq CoolSculpting device</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>The untreated flank of each subject served as the internal control.</description>
          </group>
        </group_list>
        <measure>
          <title>Mechanical Detection Threshold (MDT)</title>
          <description>MDT was evaluated using von Frey Filaments. The up-down method, which evaluates the threshold force for appearance and disappearance of a touch sensation reported by the subject, was used until 3 values were obtained. The values presented in the data table were averaged over all repeats.</description>
          <population>11 subjects were randomized to have right or left flank treated with cryolipolysis and the untreated flank served as internal control.</population>
          <units>grams</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <units_analyzed>flanks</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>flanks</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.87" lower_limit="0.4" upper_limit="1.27"/>
                    <measurement group_id="O2" value="0.4" lower_limit="0.21" upper_limit="0.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were assessed throughout the duration of the study.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Cryolipolysis</title>
          <description>Zeltiq CoolSculpting device: This is an FDA approved cooling device used for non-invasive and selective reduction of fat around the flanks, an area commonly referred to as the &quot;love handles.&quot;</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="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</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="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>
    <point_of_contact>
      <name_or_title>Dr. Lilit Garibyan</name_or_title>
      <organization>Massachusetts General Hospital</organization>
      <phone>617-726-6168</phone>
      <email>lgaribyan@partners.org</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/NCT01673113
org study id: 2012-P-001380
nct id: NCT01673113
lead sponsor: 
has dmc: No
Cryolipolysis with Zeltiq CoolSculpting device is a novel method of non-invasive fat removal.
      The technique works by application of cold plates to the skin surface for a single cooling
      cycle lasting 60 minutes, after which a cold-induced inflammatory panniculitis leads to
      selective loss of fat. There is no histologic evidence of necrotic or inflammatory damage to
      skin or nerves, however a single small human study has reported prolonged temporary altered
      sensation (hypoesthesia) in the area of cryolipolysis procedure. This hypoesthesia seen in
      about 2/3 of patients, is completely reversible, lasts up to 8 weeks after treatment, and
      suggests that cooling under these conditions can temporarily alter sensory nerve function.

      The purpose of this study is to further characterize the reversible cutaneous sensory
      function alteration after cryolipolysis with Zeltiq CoolSculpting device. Using multiple
      modalities of sensory nerve function we hope to elucidate the details of cryolipolysis
      induced sensory nerve alteration.
Study design We undertook an open-label, prospective study at the Massachusetts General
      Hospital (MGH) (Boston, USA) between December 2012 and July 2013. The study was approved by
      the MGH Institutional Research Board and was registered at ClinicalTrials.gov (NCT01673113).
      Written, informed consent was obtained from all participants prior to participation in the
      study. The study conformed to the standards set by the Declaration of Helsinki and Good
      Clinical Practice Guidelines.

      Eleven healthy subjects were enrolled in the study. They were randomized to have either the
      left or right flank treated with a single cycle of cryolipolysis. Baseline measurement of
      sensory function was evaluated using QST at the treated and control (untreated) flank for
      each subject. Histamine iontophoresis was used to evaluate itch duration and intensity on the
      treated and control flank for each subject. All sensory function testing, including responses
      to histamine-induced itch, were assessed at 48-72 hours, and Day 7, 14, 21, 35 and 56
      post-treatment. In 6 subjects, skin biopsies (3 mm diameter) for histological analysis of
      nerve fiber density at the treated flank were taken at baseline, 48-72 hours, Day 21 and 56
      post-treatment.

      Cryolipolysis procedure All subjects received cryolipolysis treatment to the flank above the
      iliac crest, on one side of the body. The untreated (contralateral) flank served as the
      control throughout the study. Subjects were randomized to have right or left flank treated
      and randomization was achieved with a computer-generated randomization code. The treatment
      site was identified, assessed and marked by a single, unblinded investigator. The sensory
      testing site within the flanks was marked and registered using a transparent plastic sheet,
      aligned using cutaneous landmarks including nevi or scars, and photographed with the subject
      in a standard position, to ensure that the same area was tested on follow-up visits.

      Cryolipolysis was performed using an EzApp6.3 applicator (CoolScultping, Zeltiq Aesthetics
      Inc, Pleasanton USA) and standard settings at cooling intensity factor (CIF) of 41.6,
      corresponding to heat transfer of -73mW/cm2, applied for one hour.

      Quantitative sensory testing (QST) The QST protocol consisted of a series of 7 sensory tests.
      The QST procedure started with the evaluation of mechanical followed by thermal thresholds.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Vibration Detection Threshold (VDT)
time frame: within 48-72 hours after treatment
description: VDT was evaluated using a computerized vibrometer with 1cm2 contact probe placed perpendicularly on the skin (TSA-II, Medoc Inc., Ramat Yishai, Israel). This device gradually increased the vibration magnitude until the subject pressed a "stop" button to indicate when they first felt the vibration. This test was repeated 8 times. The values presented in the data table were averaged over all repeats.
measure: Mechanical Detection Threshold (MDT)
time frame: 48-72 hours post treatment
description: MDT was evaluated using von Frey Filaments. The up-down method, which evaluates the threshold force for appearance and disappearance of a touch sensation reported by the subject, was used until 3 values were obtained. The values presented in the data table were averaged over all repeats.
arm group label: Cryolipolysis
arm group type: Experimental
description: All subjects were randomized to have either the left of right flank treated with single the Zeltiq CoolSculpting Device, which is an FDA approved cooling device used for non-invasive and selective reduction of fat around the flanks. Sensory testing was done before and after the procedure.
arm group label: Control
arm group type: No Intervention
description: All subjects were randomized to have either the left of right flank treated with single the Zeltiq CoolSculpting Device. The untreated flank served as the internal control for each subject.
intervention type: Device
intervention name: Zeltiq CoolSculpting device
description: This is an FDA approved cooling device used for non-invasive and selective reduction of fat around the flanks, an area commonly referred to as the "love handles."
arm group label: Cryolipolysis
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: R. Rox Anderson, MD
role: Principal Investigator
affiliation: Massachusetts General Hospital
facility: 
country: United States
url: http://www.ncbi.nlm.nih.gov/pubmed/26099028
description: the published paper
citation: Garibyan L, Cornelissen L, Sipprell W, Pruessner J, Elmariah S, Luo T, Lerner EA, Jung Y, Evans C, Zurakowski D, Berde CB, Rox Anderson R. Transient Alterations of Cutaneous Sensory Nerve Function by Noninvasive Cryolipolysis. J Invest Dermatol. 2015 Nov;135(11):2623-2631. doi: 10.1038/jid.2015.233. Epub 2015 Jun 22.
PMID: 26099028
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Richard Rox Anderson, MD
investigator title: Professor, Harvard Medical School
mesh term: Obesity
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 