<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/NCT02261597</url>
  </required_header>
  <id_info>
    <org_study_id>2014P000297</org_study_id>
    <nct_id>NCT02261597</nct_id>
  </id_info>
  <brief_title>Challenging the Inflammatory Response System in Insomnia Disorder</brief_title>
  <official_title>Challenging the Inflammatory Response System: Are Individuals With Insomnia More Reactive?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beth Israel Deaconess Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Beth Israel Deaconess Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this study is to understand how insomnia (compared to good sleep) may&#xD;
      affect the response of the body to a repeated physiological challenge, such as inserting the&#xD;
      hand in ice-cold water for several times in a row. In particular, the investigators are&#xD;
      interested in the response of markers that can be associated with stress, such as blood&#xD;
      pressure and stress hormones.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Sleep is critical for the regulation and maintenance of biological systems, and sleep&#xD;
      deficiency, such as insomnia, has been shown to be associated with elevated risks for&#xD;
      cardiovascular, metabolic, and mood disorders.&#xD;
&#xD;
      Despite the high prevalence of insomnia in the population, the investigators understanding of&#xD;
      the biological consequences of the disorder with respect to inflammatory, autonomic, and&#xD;
      stress system markers is limited, and often not consistent.&#xD;
&#xD;
      In addition, insomnia may not only alter the basal activity of these systems, but may change&#xD;
      their reactivity to other stressors and challenges. In support of this assumption are&#xD;
      findings showing that poor sleep quality in healthy individuals is associated with a stronger&#xD;
      biological response to a stressful challenge, such as the cold pressor test. This test&#xD;
      involves the immersion of the hand in ice-cold water. It is one of the most commonly used&#xD;
      laboratory physiological challenge tests, provoking not only unpleasantness, but also&#xD;
      increases in stress and inflammatory markers.&#xD;
&#xD;
      Investigations of such system's reactivity to challenge may elucidate systems abnormalities&#xD;
      that the investigators do not capture by only assessing basal system's levels. For example,&#xD;
      in patients with rheumatoid arthritis, basal inflammatory levels are normal, but the response&#xD;
      to a physiological stress challenge (cold pressor test) is amplified.&#xD;
&#xD;
      To the investigators knowledge, no studies have measured how insomnia may affect the&#xD;
      reactivity of biological systems to a stressful challenge, which may serve as an important&#xD;
      indicator of system's dysregulation and associated disease risk.&#xD;
&#xD;
      In this light, the primary goal of this proposal will investigate whether stress-related&#xD;
      systems are more reactive to a physiological stressful challenge in insomnia disorder&#xD;
      compared to healthy controls.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2015</start_date>
  <completion_date type="Actual">March 2018</completion_date>
  <primary_completion_date type="Actual">June 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Inflammatory Response to Physiological Challenge- Change in Plasma Levels of IL-6</measure>
    <time_frame>Baseline blood was obtained between 11am-12pm and prior to any Cold Pressor Tests (CPTs). Three CPTs were performed, with 1.5 hours between each one. The first CPT was done at 1pm. Blood draws were obtained 20min and 50 min after each CPT.</time_frame>
    <description>Inflammatory marker: Change in plasma levels of IL-6 (pg/mL).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Stress Reactivity to Physiological Challenge- Change in Serum Levels of Cortisol</measure>
    <time_frame>Baseline blood was obtained between 11am-12pm and prior to any Cold Pressor Tests (CPTs). Three CPTs were performed, with 1.5 hours between each one. The first CPT was done at 1pm. Blood draws were obtained 20min and 50 min after each CPT.</time_frame>
    <description>HPA marker: Change in serum cortisol levels (ug/dL)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Glucocorticoid Sensitivity- Percentage of IL-6 Positive Monocytes</measure>
    <time_frame>Monocytes are only obtained from the baseline blood draw, which occurs at 11am.</time_frame>
    <description>Percentage of IL-6 positive monocytes following stimulation with LPS (100pg/mL) and varying concentrations of Dexamethasone</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">44</enrollment>
  <condition>Insomnia</condition>
  <arm_group>
    <arm_group_label>Insomnia Disorder</arm_group_label>
    <description>Testing reactivity of stress-related systems to repeated exposure to the cold pressor test (hand immersion into ice-cold water) among participants with a clinical diagnosis of insomnia disorder.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Control</arm_group_label>
    <description>Testing reactivity of stress-related systems to repeated exposure to the cold pressor test (hand immersion into ice-cold water) among healthy participants without a diagnosis of insomnia disorder.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Cold Pressor Test</intervention_name>
    <description>Repeated immersion of hand in ice-cold water</description>
    <arm_group_label>Healthy Control</arm_group_label>
    <arm_group_label>Insomnia Disorder</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        -  Individuals suffering from insomnia disorder&#xD;
&#xD;
          -  Healthy control sleepers&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women and men between the ages 18-55 years&#xD;
&#xD;
          -  Blood chemistry in the normal range&#xD;
&#xD;
          -  BMI less than or equal to 35&#xD;
&#xD;
        Specific to insomnia group:&#xD;
&#xD;
          -  Diagnosis of insomnia disorder based on DSM-V criteria&#xD;
&#xD;
        Specific for control group:&#xD;
&#xD;
          -  Good quality and quantity sleep&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active infection/disease.&#xD;
&#xD;
          -  History of neurological, chronic pain, immune, cardiovascular, liver/kidney, or&#xD;
             metabolic disorder&#xD;
&#xD;
          -  History of psychiatric disorders within the last 6 months prior to study start&#xD;
&#xD;
          -  Sleep disorders other than insomnia&#xD;
&#xD;
          -  Reynaud's disease&#xD;
&#xD;
          -  Psychotropic, sleep, or any other medications or herbs interfering with the&#xD;
             inflammatory, autonomic, or HPA system in the last 2 weeks prior to study start,&#xD;
             except oral contraceptives&#xD;
&#xD;
          -  In psychotherapy or any other behavioral interventions at study start&#xD;
&#xD;
          -  Donation of blood or platelets within 3 months of hospital visits&#xD;
&#xD;
          -  Pregnant/nursing.&#xD;
&#xD;
          -  Substance abuse.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Haack Monika, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beth Israel Deaconess Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>BIDMC</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>October 7, 2014</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2014</study_first_posted>
  <results_first_submitted>May 3, 2018</results_first_submitted>
  <results_first_submitted_qc>March 18, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">June 17, 2019</results_first_posted>
  <last_update_submitted>July 18, 2019</last_update_submitted>
  <last_update_submitted_qc>July 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Beth Israel Deaconess Medical Center</investigator_affiliation>
    <investigator_full_name>Monika Haack</investigator_full_name>
    <investigator_title>Assistant Professor of Neurology HMS</investigator_title>
  </responsible_party>
  <keyword>insomnia, inflammation, stress</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sleep Initiation and Maintenance Disorders</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 26, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/97/NCT02261597/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Healthy Controls</title>
          <description>Healthy participants without a diagnosis of insomnia disorder visited the CRC for a one-day stay immediately following an overnight sleep screen</description>
        </group>
        <group group_id="P2">
          <title>Insomnia Disorder</title>
          <description>Participants with the diagnosis of insomnia disorder (according to DSM-V) visited the CRC for a one-day stay immediately following an overnight sleep screen</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="22"/>
              </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>
      <group_list>
        <group group_id="B1">
          <title>Healthy Controls</title>
          <description>Healthy participants without a diagnosis of insomnia disorder visited the CRC for a one-day stay immediately following an overnight sleep screen.</description>
        </group>
        <group group_id="B2">
          <title>Insomnia Disorder</title>
          <description>Participants with the diagnosis of insomnia disorder (according to DSM-V) visited the CRC for a one-day stay immediately following an overnight sleep screen.</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="22"/>
            <count group_id="B2" value="22"/>
            <count group_id="B3" value="44"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <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="22"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="44"/>
                  </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>Age</title>
          <description>Average age and age range for all participants in the study, and for each arm in the study</description>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.09" lower_limit="18" upper_limit="47"/>
                    <measurement group_id="B2" value="30.27" lower_limit="18" upper_limit="49"/>
                    <measurement group_id="B3" value="28.18" lower_limit="18" upper_limit="49"/>
                  </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="19"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="12"/>
                  </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</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>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </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="22"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Inflammatory Response to Physiological Challenge- Change in Plasma Levels of IL-6</title>
        <description>Inflammatory marker: Change in plasma levels of IL-6 (pg/mL).</description>
        <time_frame>Baseline blood was obtained between 11am-12pm and prior to any Cold Pressor Tests (CPTs). Three CPTs were performed, with 1.5 hours between each one. The first CPT was done at 1pm. Blood draws were obtained 20min and 50 min after each CPT.</time_frame>
        <population>Data of 3 participants were excluded from analysis due to development of headache or Iv problems in the course of the experimental study day.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Controls</title>
            <description>Healthy participants without a diagnosis of insomnia disorder visited the CRC for a one-day stay immediately following an overnight sleep screen</description>
          </group>
          <group group_id="O2">
            <title>Insomnia Disorder</title>
            <description>Participants with the diagnosis of insomnia disorder (according to DSM-V) visited the CRC for a one-day stay immediately following an overnight sleep screen</description>
          </group>
        </group_list>
        <measure>
          <title>Inflammatory Response to Physiological Challenge- Change in Plasma Levels of IL-6</title>
          <description>Inflammatory marker: Change in plasma levels of IL-6 (pg/mL).</description>
          <population>Data of 3 participants were excluded from analysis due to development of headache or Iv problems in the course of the experimental study day.</population>
          <units>pg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5013" spread="0.16892"/>
                    <measurement group_id="O2" value="2.1626" spread="0.67566"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20min after CPT 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.5911" spread="0.49528"/>
                    <measurement group_id="O2" value="2.7269" spread="0.5303"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>50 min after CPT 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0318" spread="0.55967"/>
                    <measurement group_id="O2" value="2.7556" spread="0.31272"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20 min after CPT 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.7131" spread="0.65019"/>
                    <measurement group_id="O2" value="3.8603" spread="0.53619"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>50 min after CPT 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.2044" spread="0.64394"/>
                    <measurement group_id="O2" value="3.3381" spread="0.4539"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20 min after CPT 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.514" spread="0.82173"/>
                    <measurement group_id="O2" value="5.1606" spread="0.95047"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>50 min after CPT 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.9841" spread="1.15086"/>
                    <measurement group_id="O2" value="4.3278" spread="0.75218"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Stress Reactivity to Physiological Challenge- Change in Serum Levels of Cortisol</title>
        <description>HPA marker: Change in serum cortisol levels (ug/dL)</description>
        <time_frame>Baseline blood was obtained between 11am-12pm and prior to any Cold Pressor Tests (CPTs). Three CPTs were performed, with 1.5 hours between each one. The first CPT was done at 1pm. Blood draws were obtained 20min and 50 min after each CPT.</time_frame>
        <population>Data of 3 participants were excluded from analysis due to development of headache or Iv problems in the course of the experimental study day.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Controls</title>
            <description>Healthy participants without a diagnosis of insomnia disorder visited the CRC for a one-day stay immediately following an overnight sleep screen</description>
          </group>
          <group group_id="O2">
            <title>Insomnia Disorder</title>
            <description>Participants with the diagnosis of insomnia disorder (according to DSM-V) visited the CRC for a one-day stay immediately following an overnight sleep screen</description>
          </group>
        </group_list>
        <measure>
          <title>Stress Reactivity to Physiological Challenge- Change in Serum Levels of Cortisol</title>
          <description>HPA marker: Change in serum cortisol levels (ug/dL)</description>
          <population>Data of 3 participants were excluded from analysis due to development of headache or Iv problems in the course of the experimental study day.</population>
          <units>ug/dL</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.9948" spread="1.00453"/>
                    <measurement group_id="O2" value="9.8250" spread="0.92339"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20min after CPT 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.6695" spread="0.61099"/>
                    <measurement group_id="O2" value="13.95" spread="1.22551"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>50 min after CPT 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.3255" spread="0.47898"/>
                    <measurement group_id="O2" value="11.0416" spread="0.95435"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20 min after CPT 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.448" spread="0.57976"/>
                    <measurement group_id="O2" value="10.9342" spread="1.13843"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>50 min after CPT 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.452" spread="0.39262"/>
                    <measurement group_id="O2" value="8.6063" spread="0.98503"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20 min after CPT 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.7545" spread="0.71965"/>
                    <measurement group_id="O2" value="9.9168" spread="1.27366"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>50 min after CPT 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.651" spread="0.40265"/>
                    <measurement group_id="O2" value="8.4684" spread="1.01139"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Glucocorticoid Sensitivity- Percentage of IL-6 Positive Monocytes</title>
        <description>Percentage of IL-6 positive monocytes following stimulation with LPS (100pg/mL) and varying concentrations of Dexamethasone</description>
        <time_frame>Monocytes are only obtained from the baseline blood draw, which occurs at 11am.</time_frame>
        <population>Data of 2 participants were excluded from analysis due to development of headache or Iv problems in the course of the experimental study day.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Controls</title>
            <description>Healthy participants without a diagnosis of insomnia disorder visited the CRC for a one-day stay immediately following an overnight sleep screen</description>
          </group>
          <group group_id="O2">
            <title>Insomnia Disorder</title>
            <description>Participants with the diagnosis of insomnia disorder (according to DSM-V) visited the CRC for a one-day stay immediately following an overnight sleep screen</description>
          </group>
        </group_list>
        <measure>
          <title>Glucocorticoid Sensitivity- Percentage of IL-6 Positive Monocytes</title>
          <description>Percentage of IL-6 positive monocytes following stimulation with LPS (100pg/mL) and varying concentrations of Dexamethasone</description>
          <population>Data of 2 participants were excluded from analysis due to development of headache or Iv problems in the course of the experimental study day.</population>
          <units>Percentage of IL-6 positive monocytes</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.659" spread="2.9058"/>
                    <measurement group_id="O2" value="17.250" spread="1.9317"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected over a 9-hour period for each particpant.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Healthy Controls</title>
          <description>Healthy participants without a diagnosis of insomnia disorder visited the CRC for a one-day stay immediately following an overnight sleep screen</description>
        </group>
        <group group_id="E2">
          <title>Insomnia Disorder</title>
          <description>Participants with the diagnosis of insomnia disorder (DSM-V) visited the CRC for a one-day stay immediately following an overnight sleep screen.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
              </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="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
              </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>
    <point_of_contact>
      <name_or_title>Dr. Monika Haack</name_or_title>
      <organization>Beth Israel Deaconess Medical Center, Harvard Medical School</organization>
      <phone>617-667-5234</phone>
      <email>mhaack@bidmc.harvard.edu</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/NCT02261597
org study id: 2014P000297
nct id: NCT02261597
lead sponsor: 
has dmc: No
The main purpose of this study is to understand how insomnia (compared to good sleep) may
      affect the response of the body to a repeated physiological challenge, such as inserting the
      hand in ice-cold water for several times in a row. In particular, the investigators are
      interested in the response of markers that can be associated with stress, such as blood
      pressure and stress hormones.
Sleep is critical for the regulation and maintenance of biological systems, and sleep
      deficiency, such as insomnia, has been shown to be associated with elevated risks for
      cardiovascular, metabolic, and mood disorders.

      Despite the high prevalence of insomnia in the population, the investigators understanding of
      the biological consequences of the disorder with respect to inflammatory, autonomic, and
      stress system markers is limited, and often not consistent.

      In addition, insomnia may not only alter the basal activity of these systems, but may change
      their reactivity to other stressors and challenges. In support of this assumption are
      findings showing that poor sleep quality in healthy individuals is associated with a stronger
      biological response to a stressful challenge, such as the cold pressor test. This test
      involves the immersion of the hand in ice-cold water. It is one of the most commonly used
      laboratory physiological challenge tests, provoking not only unpleasantness, but also
      increases in stress and inflammatory markers.

      Investigations of such system's reactivity to challenge may elucidate systems abnormalities
      that the investigators do not capture by only assessing basal system's levels. For example,
      in patients with rheumatoid arthritis, basal inflammatory levels are normal, but the response
      to a physiological stress challenge (cold pressor test) is amplified.

      To the investigators knowledge, no studies have measured how insomnia may affect the
      reactivity of biological systems to a stressful challenge, which may serve as an important
      indicator of system's dysregulation and associated disease risk.

      In this light, the primary goal of this proposal will investigate whether stress-related
      systems are more reactive to a physiological stressful challenge in insomnia disorder
      compared to healthy controls.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Inflammatory Response to Physiological Challenge- Change in Plasma Levels of IL-6
time frame: Baseline blood was obtained between 11am-12pm and prior to any Cold Pressor Tests (CPTs). Three CPTs were performed, with 1.5 hours between each one. The first CPT was done at 1pm. Blood draws were obtained 20min and 50 min after each CPT.
description: Inflammatory marker: Change in plasma levels of IL-6 (pg/mL).
measure: Stress Reactivity to Physiological Challenge- Change in Serum Levels of Cortisol
time frame: Baseline blood was obtained between 11am-12pm and prior to any Cold Pressor Tests (CPTs). Three CPTs were performed, with 1.5 hours between each one. The first CPT was done at 1pm. Blood draws were obtained 20min and 50 min after each CPT.
description: HPA marker: Change in serum cortisol levels (ug/dL)
measure: Glucocorticoid Sensitivity- Percentage of IL-6 Positive Monocytes
time frame: Monocytes are only obtained from the baseline blood draw, which occurs at 11am.
description: Percentage of IL-6 positive monocytes following stimulation with LPS (100pg/mL) and varying concentrations of Dexamethasone
arm group label: Insomnia Disorder
description: Testing reactivity of stress-related systems to repeated exposure to the cold pressor test (hand immersion into ice-cold water) among participants with a clinical diagnosis of insomnia disorder.
arm group label: Healthy Control
description: Testing reactivity of stress-related systems to repeated exposure to the cold pressor test (hand immersion into ice-cold water) among healthy participants without a diagnosis of insomnia disorder.
intervention type: Behavioral
intervention name: Cold Pressor Test
description: Repeated immersion of hand in ice-cold water
arm group label: Healthy Control
arm group label: Insomnia Disorder
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Haack Monika, PhD
role: Principal Investigator
affiliation: Beth Israel Deaconess Medical Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Beth Israel Deaconess Medical Center
investigator full name: Monika Haack
investigator title: Assistant Professor of Neurology HMS
mesh term: Sleep Initiation and Maintenance Disorders
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 