<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/NCT01700725</url>
  </required_header>
  <id_info>
    <org_study_id>GW100054 US Dept of Defense</org_study_id>
    <secondary_id>2011-0843</secondary_id>
    <nct_id>NCT01700725</nct_id>
  </id_info>
  <brief_title>Gulf War Illness Nasal Irrigation Study</brief_title>
  <acronym>GWINIS</acronym>
  <official_title>Nasal Irrigation for Chronic Rhinosinusitis and Fatigue in Patients With Gulf War Illness</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Wisconsin, Madison</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Wisconsin, Madison</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether nasal irrigation with Xylitol or saline are&#xD;
      effective in the treatment of chronic rhinosinusitis and fatigue symptoms associated with&#xD;
      Gulf War Illness.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: Gulf War Illness (GWI) results in tremendous impact to quality of life. Symptoms&#xD;
      of chronic rhinosinusitis (CRS) and fatigue are the first (47%) and third (41%) most common&#xD;
      symptoms of patients with GWI, respectively. These symptoms are biologically characterized by&#xD;
      a milieu of elevated levels of proinflammatory cytokines; to date, the profile of these&#xD;
      cytokines in serum and nasal secretions is incompletely understood and has not been assessed&#xD;
      in response to therapy. Nasal irrigation (NI) is a therapy which bathes the nasal cavity with&#xD;
      a solution (liquid). There are two promising forms of NI; saline NI (S-NI) is hypothesized to&#xD;
      improve sinus symptoms by thinning and clearing mucus and inflammatory mediators, decreasing&#xD;
      mucosal edema and improving ciliary function. Xylitol NI (X-NI) has been shown to change the&#xD;
      salinity of the mucosal surface resulting in enhanced antimicrobial properties. Although NI&#xD;
      is an evidence-based adjunctive therapy for CRS and has been reported to be effective for CRS&#xD;
      and fatigue, it has not been assessed in a GWI population.&#xD;
&#xD;
      Specific Aims, Hypotheses and Study Design: The specific aims of this proposal are to&#xD;
      determine whether routine care plus S-NI, or X-NI, compared to routine care alone, result in&#xD;
      improved health-related quality of life (HRQoL), are cost-effective and decrease&#xD;
      proinflammatory bias in subjects with GWI who suffer from CRS and fatigue.&#xD;
&#xD;
      Consistent with our specific aims, we will test the following hypotheses: In an RCT setting,&#xD;
      at 26 weeks post-enrollment, adults with GWI and symptoms of CRI and fatigue, treated with&#xD;
      routine care plus S-NI or X-NI, compared to those treated with routine care alone, will&#xD;
      demonstrate:&#xD;
&#xD;
      H1: improved HRQoL: a) sinus-disease specific HRQoL as evaluated by the validated Sinonasal&#xD;
      Outcomes Test (SNOT-20) questionnaire (primary outcome measure); b) fatigue-specific HRQoL as&#xD;
      assessed by the validated questionnaire, the Multidimensional Fatigue Inventory (MFI); and c)&#xD;
      overall HRQoL as assessed by the validated questionnaire the Medical Outcomes Survey Short&#xD;
      Form-36 (SF-36; mental and physical health domains) augmented with 18 sleep- and breathing&#xD;
      related questions.&#xD;
&#xD;
      H.2: greater cost-effectiveness as measured by the average cost of the intervention divided&#xD;
      by the average effectiveness (as assessed by a improvement in SNOT-20 scores), and reported&#xD;
      as the &quot;dollars spent per subject restored to health.&quot;&#xD;
&#xD;
      H.3: improved treatment satisfaction as assessed by a single-item treatment satisfaction&#xD;
      score and a qualitative exit interview.&#xD;
&#xD;
      H.4: improved proinflammatory bias: a) reduced activation and dysregulation of&#xD;
      proinflammatory pathways as determined by a reduction in URI-specific inflammatory cytokines&#xD;
      in serum and nasal secretions; and b) improved serum-based complete blood count,&#xD;
      sedimentation rate or C-reactive protein, or nasal swab-based neutrophil or eosinophil&#xD;
      counts.&#xD;
&#xD;
      Study Design: 26 week duration of follow-up, 3-arm RCT (N=75). All groups will utilize&#xD;
      routine care for their GWI and symptoms of CRS and fatigue. Groups 1 and 2 will in addition&#xD;
      add S-NI or X-NI twice daily to their routine care, respectively. Group 3 will continue to&#xD;
      use routine care with no other additions (control group); control group participants will be&#xD;
      offered NI training and related materials (xylitol or saline per subject preference) after&#xD;
      they complete their 26-week follow-up period.&#xD;
&#xD;
      Impact: Positive findings would suggest a number of important effects:&#xD;
&#xD;
        -  Statistically positive results on HRQoL outcome measures would suggest that NI can&#xD;
           provide effective adjunctive therapy for CRS and fatigue in adults with GWI, improving&#xD;
           health of affected patients and potentially providing gains to society through reduced&#xD;
           health care utilization and absenteeism related costs.&#xD;
&#xD;
        -  Positive biomarker findings would contribute to our better understanding of the etiology&#xD;
           of CRS and fatigue in the GWI population and of possible biological pathways underlying&#xD;
           the NI efficacy.&#xD;
&#xD;
        -  The finding that either form of NI is cost effective would provide economic&#xD;
           justification for its clinical use.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2012</start_date>
  <completion_date type="Actual">May 2017</completion_date>
  <primary_completion_date type="Actual">June 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Sino-Nasal Outcome Test (SNOT-20) Score From Baseline</measure>
    <time_frame>Change from baseline week 8, change from baseline week 26</time_frame>
    <description>Sino-Nasal Outcome Test (SNOT-20) is a recommended tool for clinical trial research involving CRS. Sinus disease specific quality of life will be measured using the total score of this validated 20 item questionnaire. It is a reliable and valid outcome measure for patients with CRS (Cronbach's α 0.9, test-retest r = 0.9) that describes the health burden and is sensitive to clinical change. Patients who are more affected by CRS tend to have greater SNOT-20 scores (P &lt; 0.01). The SNOT-20 score is expected to improve in NI-treated subjects compared to controls. Findings of the PI's prior RCT of adults with CRS are consistent with the above evidence. The total range of possible scores is 0-100. The higher the score, the worse the symptoms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Multidimensional Fatigue Inventory (MFI) Over Baseline</measure>
    <time_frame>Baseline to weeks 8 &amp; 26</time_frame>
    <description>The Multidimensional Fatigue Inventory is a validated disease specific outcome measure for fatigue. The instrument has good internal consistency (average Cronbach's alpha 0.84). Construct validity was established after comparisons between and within groups, assuming differences in fatigue based on differences in circumstances and/or activity level. Convergent validity was investigated by correlating the MFI-scales with a Visual Analogue Scale measuring fatigue. Fatigue is expected to improve in the NI-treated patients compared to controls. The total range of possible scores is 0-100. The higher the score, the more fatigue.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Medical Outcomes Survey Short Form-36 (SF-36) Over Baseline</measure>
    <time_frame>Baseline and weeks 8 &amp; 26</time_frame>
    <description>SF-36 is a validated questionnaire designed to assess health status, function and overall health related quality of life. The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. Gulf War Illness and chronic rhinosinusitis both affect sleep and breathing parameters. Prior studies suggest that both may be improved with SNI in some subjects. Eighteen relevant sleep and breathing related questions to the SF-36. The total range is 0-100. The lower the score, the more disability.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Persian Gulf Syndrome</condition>
  <condition>Chronic Sinusitis</condition>
  <condition>Fatigue</condition>
  <condition>Acute Sinusitis</condition>
  <arm_group>
    <arm_group_label>Nasal Irrigation - Saline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>nasal irrigation using saline plus routine care for symptoms of CRS and fatigue</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Nasal Irrigation - Xylitol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nasal Irrigation with Xylitol plus routine care for symptoms of CRS and fatigue</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Control group subjects continue to use routine care only</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Nasal Irrigation - Saline</intervention_name>
    <description>Liquid-based nasal irrigation (NI) is performed using a nasal irrigation cup (&quot;neti pot&quot;), a simple hand-held vessel that uses the force of gravity to gently irrigate the user's nasal cavity. Subjects will be requested to perform NI twice daily. The subjects will prepare the saline solution by themselves using the study-provided kit which will include packets of salt powder and the neti pot; subjects will dissolve the powder in lukewarm tap water to achieve a 2% buffered saline solution. The solution is then delivered to the nasal cavity using neti pot.</description>
    <arm_group_label>Nasal Irrigation - Saline</arm_group_label>
    <other_name>2% buffered saline</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nasal Irrigation - Xylitol</intervention_name>
    <description>Liquid-based nasal irrigation (NI) is performed using a nasal irrigation cup (&quot;neti pot&quot;), a simple hand-held vessel that uses the force of gravity to gently irrigate the user's nasal cavity. Subjects will be requested to perform NI twice daily. The subjects will prepare the Xylitol solution by themselves using the study-provided kit which will include packets of Xylitol powder and the neti pot; subjects will dissolve the powder in lukewarm tap water to achieve a 5% Xylitol solution. The solution is then delivered to the nasal cavity using neti pot.</description>
    <arm_group_label>Nasal Irrigation - Xylitol</arm_group_label>
    <other_name>5% Xylitol solution</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  English fluency and basic reading and writing literacy.&#xD;
&#xD;
          -  Deployment to the Persian Gulf (e.g., Iraq, Kuwait, Saudi Arabia) for the purpose of&#xD;
             Operation Desert Shield or Operation Desert Storm during the first Gulf War&#xD;
             (1990-1991).&#xD;
&#xD;
          -  Meeting criteria for a diagnosis of GWI as based on the &quot;Kansas&quot; GWI case definition;&#xD;
             only the Kansas case definition (from among the several currently used case&#xD;
             definitions) can differentiate between Gulf War-deployed and non-deployed Gulf era&#xD;
             veterans.&#xD;
&#xD;
          -  Meeting criteria for a diagnosis of chronic rhinosinusitis (CRS) using self-reported&#xD;
             symptoms and based on clinical guidelines; eligible subjects will report: • sinonasal&#xD;
             symptoms for at least 12 weeks; • a constellation of sinonasal symptoms including&#xD;
             either two or more major factors, or 1 major and 2 minor factors (see Table 1 below),&#xD;
             or chronic nasal purulence for 12 or more weeks; and • a moderate to severe HRQoL&#xD;
             impact (≥ 3 points on a 0-10 Likert severity scale) as assessed by a single item&#xD;
             question:11 &quot;What has been the average level of your sinus symptoms daily over the&#xD;
             past month on a 0-10 scale?&quot; This item is consistent with eligibility criteria used in&#xD;
             prior NI studies.&#xD;
&#xD;
          -  Chronic fatigue of moderate-to-severe severity defined as scoring at least 3 points on&#xD;
             a single question (0-10 Likert scale): &quot;What has been the average level of your daily&#xD;
             fatigue over the past month on a 0-10 scale?&quot;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Self-reported pregnancy.&#xD;
&#xD;
          -  Current use of liquid NI or xylitol nasal spray; regular use is defined as 1 or more&#xD;
             irrigations weekly for 3 consecutive weeks.&#xD;
&#xD;
          -  Self-reported neurological or musculoskeletal conditions that could facilitate&#xD;
             aspiration, or patients who otherwise cannot physically perform the NI procedure.&#xD;
&#xD;
          -  Self-reported borderline personality disorder.&#xD;
&#xD;
          -  Inability or stated reluctance to reliably participate in study activities.&#xD;
&#xD;
          -  Severe or unstable mental health problems that would preclude safe or reliable study&#xD;
             participation as based on an in-person evaluation by a psychiatry team; active&#xD;
             delusional disorder, depressive disorder or alcohol/drug abuse or dependence will be a&#xD;
             primary target of this interview using both a structured clinical interview (MINI ref)&#xD;
             and psychiatry team evaluation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rachel Molander, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>US Department of Veterans Affairs, William S. Middleton Memorial Veterans Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>David P Rabago, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Wisconsin, Madison</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Wisconsin General Clinical Research Center</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>August 14, 2012</study_first_submitted>
  <study_first_submitted_qc>October 1, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 4, 2012</study_first_posted>
  <results_first_submitted>April 9, 2019</results_first_submitted>
  <results_first_submitted_qc>May 3, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">May 21, 2019</results_first_posted>
  <last_update_submitted>May 3, 2019</last_update_submitted>
  <last_update_submitted_qc>May 3, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 21, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Gulf War Illness</keyword>
  <keyword>xylitol</keyword>
  <keyword>nasal irrigation</keyword>
  <keyword>Desert Storm</keyword>
  <keyword>Persian Gulf Conflicts</keyword>
  <keyword>neti pot</keyword>
  <keyword>cytokines</keyword>
  <keyword>nasal mucus</keyword>
  <keyword>inflammatory mediator</keyword>
  <keyword>lactoferrin</keyword>
  <keyword>lysozyme</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sinusitis</mesh_term>
    <mesh_term>Fatigue</mesh_term>
    <mesh_term>Persian Gulf Syndrome</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Nasal Irrigation - Xylitol</title>
          <description>Nasal Irrigation with Xylitol plus routine care for symptoms of CRS and fatigue</description>
        </group>
        <group group_id="P2">
          <title>Nasal Irrigation - Saline</title>
          <description>Nasal irrigation using saline plus routine care for symptoms of CRS and fatigue</description>
        </group>
        <group group_id="P3">
          <title>Control Group</title>
          <description>Control group subjects continue to use routine care only</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Nasal Irrigation - Xylitol</title>
          <description>Nasal Irrigation with Xylitol plus routine care for symptoms of CRS and fatigue</description>
        </group>
        <group group_id="B2">
          <title>Nasal Irrigation - Saline</title>
          <description>Nasal irrigation using saline plus routine care for symptoms of CRS and fatigue</description>
        </group>
        <group group_id="B3">
          <title>Control Group</title>
          <description>Control group subjects continue to use routine care only</description>
        </group>
        <group group_id="B4">
          <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="14"/>
            <count group_id="B2" value="14"/>
            <count group_id="B3" value="12"/>
            <count group_id="B4" value="40"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="53.7" spread="9.2"/>
                    <measurement group_id="B2" value="52.7" spread="6.7"/>
                    <measurement group_id="B3" value="55.0" spread="7.7"/>
                    <measurement group_id="B4" value="53.8" spread="7.8"/>
                  </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="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Non-Hispanic White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White Hispanic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pacific Islander / Hawaiian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Multiple Races</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </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="14"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Education</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Highschool or Less</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Some College</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>College Graduate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sinusitis Symptoms</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20.5" spread="7.8"/>
                    <measurement group_id="B2" value="16.4" spread="9.9"/>
                    <measurement group_id="B3" value="22.4" spread="2.3"/>
                    <measurement group_id="B4" value="19.8" spread="7.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Fatigue</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19.3" spread="8.4"/>
                    <measurement group_id="B2" value="19.9" spread="6.0"/>
                    <measurement group_id="B3" value="23.8" spread="3.1"/>
                    <measurement group_id="B4" value="20.7" spread="6.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>SNOT-20</title>
          <description>Sinus disease specific quality of life will be measured using the total score of this validated 20 item questionnaire. It is a reliable and valid outcome measure for patients with CRS (Cronbach's α 0.9, test-retest r = 0.9) that describes the health burden and is sensitive to clinical change. Patients who are more affected by CRS tend to have greater SNOT-20 scores (P &lt; 0.01). The SNOT-20 score is expected to improve in NI-treated subjects compared to controls.The total range of possible scores is 0-100. The higher the score, the worse the symptoms.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="50.8" spread="14.7"/>
                    <measurement group_id="B2" value="47.6" spread="13.7"/>
                    <measurement group_id="B3" value="47.2" spread="8.7"/>
                    <measurement group_id="B4" value="48.5" spread="12.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>SF-36</title>
          <description>SF-36 is a validated questionnaire designed to assess health status, function and overall health related quality of life. It includes one multi-item scale assessing 8 areas: 1) limitations in physical activities; 2) limitations in social activities; 3) limitations in usual role activities (physical problems); 4) bodily pain; 5) general mental health; 6) limitations in usual role activities (emotional problems); 7) vitality; and 8) general health perceptions. Eighteen relevant sleep and breathing related questions to the SF-36. The total range is 0-100. The lower the score, the more disability.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="51.1" spread="15.8"/>
                    <measurement group_id="B2" value="59.0" spread="17.6"/>
                    <measurement group_id="B3" value="62.7" spread="14.1"/>
                    <measurement group_id="B4" value="57.3" spread="16.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>MFI</title>
          <description>The Multidimensional Fatigue Inventory is a validated disease specific outcome measure for fatigue. The instrument has good internal consistency (average Cronbach's alpha 0.84). Fatigue is expected to improve in the NI-treated patients compared to controls. The total range of possible scores is 0-100. The higher the score, the more fatigue.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.4" spread="5.4"/>
                    <measurement group_id="B2" value="60.5" spread="6.0"/>
                    <measurement group_id="B3" value="61.7" spread="4.7"/>
                    <measurement group_id="B4" value="60.4" spread="5.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Sino-Nasal Outcome Test (SNOT-20) Score From Baseline</title>
        <description>Sino-Nasal Outcome Test (SNOT-20) is a recommended tool for clinical trial research involving CRS. Sinus disease specific quality of life will be measured using the total score of this validated 20 item questionnaire. It is a reliable and valid outcome measure for patients with CRS (Cronbach's α 0.9, test-retest r = 0.9) that describes the health burden and is sensitive to clinical change. Patients who are more affected by CRS tend to have greater SNOT-20 scores (P &lt; 0.01). The SNOT-20 score is expected to improve in NI-treated subjects compared to controls. Findings of the PI's prior RCT of adults with CRS are consistent with the above evidence. The total range of possible scores is 0-100. The higher the score, the worse the symptoms.</description>
        <time_frame>Change from baseline week 8, change from baseline week 26</time_frame>
        <population>Data from one participant in the control group and two participants in the Saline group at 26 weeks was unable to be collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Nasal Irrigation - Xylitol</title>
            <description>Nasal Irrigation with Xylitol plus routine care for symptoms of CRS and fatigue</description>
          </group>
          <group group_id="O2">
            <title>Nasal Irrigation - Saline</title>
            <description>Nasal irrigation using saline plus routine care for symptoms of CRS and fatigue</description>
          </group>
          <group group_id="O3">
            <title>Control Group</title>
            <description>Control group subjects continue to use routine care only</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Sino-Nasal Outcome Test (SNOT-20) Score From Baseline</title>
          <description>Sino-Nasal Outcome Test (SNOT-20) is a recommended tool for clinical trial research involving CRS. Sinus disease specific quality of life will be measured using the total score of this validated 20 item questionnaire. It is a reliable and valid outcome measure for patients with CRS (Cronbach's α 0.9, test-retest r = 0.9) that describes the health burden and is sensitive to clinical change. Patients who are more affected by CRS tend to have greater SNOT-20 scores (P &lt; 0.01). The SNOT-20 score is expected to improve in NI-treated subjects compared to controls. Findings of the PI's prior RCT of adults with CRS are consistent with the above evidence. The total range of possible scores is 0-100. The higher the score, the worse the symptoms.</description>
          <population>Data from one participant in the control group and two participants in the Saline group at 26 weeks was unable to be collected.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="14"/>
                    <count group_id="O3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-16.9" spread="4.9"/>
                    <measurement group_id="O2" value="-8.8" spread="5.0"/>
                    <measurement group_id="O3" value="-3.4" spread="5.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="12"/>
                    <count group_id="O3" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-18.9" spread="4.9"/>
                    <measurement group_id="O2" value="-16.9" spread="5.3"/>
                    <measurement group_id="O3" value="-3.5" spread="5.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Multidimensional Fatigue Inventory (MFI) Over Baseline</title>
        <description>The Multidimensional Fatigue Inventory is a validated disease specific outcome measure for fatigue. The instrument has good internal consistency (average Cronbach's alpha 0.84). Construct validity was established after comparisons between and within groups, assuming differences in fatigue based on differences in circumstances and/or activity level. Convergent validity was investigated by correlating the MFI-scales with a Visual Analogue Scale measuring fatigue. Fatigue is expected to improve in the NI-treated patients compared to controls. The total range of possible scores is 0-100. The higher the score, the more fatigue.</description>
        <time_frame>Baseline to weeks 8 &amp; 26</time_frame>
        <population>Data from several participants was unable to be collected at various timepoints.</population>
        <group_list>
          <group group_id="O1">
            <title>Nasal Irrigation - Xylitol</title>
            <description>Nasal Irrigation with Xylitol plus routine care for symptoms of CRS and fatigue</description>
          </group>
          <group group_id="O2">
            <title>Nasal Irrigation - Saline</title>
            <description>Nasal irrigation using saline plus routine care for symptoms of CRS and fatigue</description>
          </group>
          <group group_id="O3">
            <title>Control Group</title>
            <description>Control group subjects continue to use routine care only</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Multidimensional Fatigue Inventory (MFI) Over Baseline</title>
          <description>The Multidimensional Fatigue Inventory is a validated disease specific outcome measure for fatigue. The instrument has good internal consistency (average Cronbach's alpha 0.84). Construct validity was established after comparisons between and within groups, assuming differences in fatigue based on differences in circumstances and/or activity level. Convergent validity was investigated by correlating the MFI-scales with a Visual Analogue Scale measuring fatigue. Fatigue is expected to improve in the NI-treated patients compared to controls. The total range of possible scores is 0-100. The higher the score, the more fatigue.</description>
          <population>Data from several participants was unable to be collected at various timepoints.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="14"/>
                    <count group_id="O3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" spread="2.4"/>
                    <measurement group_id="O2" value="0.9" spread="2.3"/>
                    <measurement group_id="O3" value="0.5" spread="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="12"/>
                    <count group_id="O3" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.9" spread="2.8"/>
                    <measurement group_id="O2" value="-1.4" spread="2.4"/>
                    <measurement group_id="O3" value="10.4" spread="3.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Medical Outcomes Survey Short Form-36 (SF-36) Over Baseline</title>
        <description>SF-36 is a validated questionnaire designed to assess health status, function and overall health related quality of life. The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. Gulf War Illness and chronic rhinosinusitis both affect sleep and breathing parameters. Prior studies suggest that both may be improved with SNI in some subjects. Eighteen relevant sleep and breathing related questions to the SF-36. The total range is 0-100. The lower the score, the more disability.</description>
        <time_frame>Baseline and weeks 8 &amp; 26</time_frame>
        <population>Data from one participant at 26 weeks in the control group was unable to be collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Nasal Irrigation - Xylitol</title>
            <description>Nasal Irrigation with Xylitol plus routine care for symptoms of CRS and fatigue</description>
          </group>
          <group group_id="O2">
            <title>Nasal Irrigation - Saline</title>
            <description>Nasal irrigation using saline plus routine care for symptoms of CRS and fatigue</description>
          </group>
          <group group_id="O3">
            <title>Control Group</title>
            <description>Control group subjects continue to use routine care only</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Medical Outcomes Survey Short Form-36 (SF-36) Over Baseline</title>
          <description>SF-36 is a validated questionnaire designed to assess health status, function and overall health related quality of life. The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. Gulf War Illness and chronic rhinosinusitis both affect sleep and breathing parameters. Prior studies suggest that both may be improved with SNI in some subjects. Eighteen relevant sleep and breathing related questions to the SF-36. The total range is 0-100. The lower the score, the more disability.</description>
          <population>Data from one participant at 26 weeks in the control group was unable to be collected.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="14"/>
                    <count group_id="O3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1" spread="3.5"/>
                    <measurement group_id="O2" value="3.9" spread="3.6"/>
                    <measurement group_id="O3" value="-0.1" spread="3.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="14"/>
                    <count group_id="O3" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.4" spread="3.5"/>
                    <measurement group_id="O2" value="7.3" spread="3.6"/>
                    <measurement group_id="O3" value="2.0" spread="4.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 26 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Nasal Irrigation - Xylitol</title>
          <description>Nasal Irrigation with Xylitol plus routine care for symptoms of CRS and fatigue</description>
        </group>
        <group group_id="E2">
          <title>Nasal Irrigation - Saline</title>
          <description>Nasal irrigation using saline plus routine care for symptoms of CRS and fatigue</description>
        </group>
        <group group_id="E3">
          <title>Control Group</title>
          <description>Control group subjects continue to use routine care only</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="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </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="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </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>David Rabago, MD</name_or_title>
      <organization>University of Wisconsin - Madison</organization>
      <phone>608-843-0850</phone>
      <email>david.rabago@fammed.wisc.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/NCT01700725
org study id: GW100054 US Dept of Defense
secondary id: 2011-0843
nct id: NCT01700725
lead sponsor: 
has dmc: No
The purpose of this study is to determine whether nasal irrigation with Xylitol or saline are
      effective in the treatment of chronic rhinosinusitis and fatigue symptoms associated with
      Gulf War Illness.
Background: Gulf War Illness (GWI) results in tremendous impact to quality of life. Symptoms
      of chronic rhinosinusitis (CRS) and fatigue are the first (47%) and third (41%) most common
      symptoms of patients with GWI, respectively. These symptoms are biologically characterized by
      a milieu of elevated levels of proinflammatory cytokines; to date, the profile of these
      cytokines in serum and nasal secretions is incompletely understood and has not been assessed
      in response to therapy. Nasal irrigation (NI) is a therapy which bathes the nasal cavity with
      a solution (liquid). There are two promising forms of NI; saline NI (S-NI) is hypothesized to
      improve sinus symptoms by thinning and clearing mucus and inflammatory mediators, decreasing
      mucosal edema and improving ciliary function. Xylitol NI (X-NI) has been shown to change the
      salinity of the mucosal surface resulting in enhanced antimicrobial properties. Although NI
      is an evidence-based adjunctive therapy for CRS and has been reported to be effective for CRS
      and fatigue, it has not been assessed in a GWI population.

      Specific Aims, Hypotheses and Study Design: The specific aims of this proposal are to
      determine whether routine care plus S-NI, or X-NI, compared to routine care alone, result in
      improved health-related quality of life (HRQoL), are cost-effective and decrease
      proinflammatory bias in subjects with GWI who suffer from CRS and fatigue.

      Consistent with our specific aims, we will test the following hypotheses: In an RCT setting,
      at 26 weeks post-enrollment, adults with GWI and symptoms of CRI and fatigue, treated with
      routine care plus S-NI or X-NI, compared to those treated with routine care alone, will
      demonstrate:

      H1: improved HRQoL: a) sinus-disease specific HRQoL as evaluated by the validated Sinonasal
      Outcomes Test (SNOT-20) questionnaire (primary outcome measure); b) fatigue-specific HRQoL as
      assessed by the validated questionnaire, the Multidimensional Fatigue Inventory (MFI); and c)
      overall HRQoL as assessed by the validated questionnaire the Medical Outcomes Survey Short
      Form-36 (SF-36; mental and physical health domains) augmented with 18 sleep- and breathing
      related questions.

      H.2: greater cost-effectiveness as measured by the average cost of the intervention divided
      by the average effectiveness (as assessed by a improvement in SNOT-20 scores), and reported
      as the "dollars spent per subject restored to health."

      H.3: improved treatment satisfaction as assessed by a single-item treatment satisfaction
      score and a qualitative exit interview.

      H.4: improved proinflammatory bias: a) reduced activation and dysregulation of
      proinflammatory pathways as determined by a reduction in URI-specific inflammatory cytokines
      in serum and nasal secretions; and b) improved serum-based complete blood count,
      sedimentation rate or C-reactive protein, or nasal swab-based neutrophil or eosinophil
      counts.

      Study Design: 26 week duration of follow-up, 3-arm RCT (N=75). All groups will utilize
      routine care for their GWI and symptoms of CRS and fatigue. Groups 1 and 2 will in addition
      add S-NI or X-NI twice daily to their routine care, respectively. Group 3 will continue to
      use routine care with no other additions (control group); control group participants will be
      offered NI training and related materials (xylitol or saline per subject preference) after
      they complete their 26-week follow-up period.

      Impact: Positive findings would suggest a number of important effects:

        -  Statistically positive results on HRQoL outcome measures would suggest that NI can
           provide effective adjunctive therapy for CRS and fatigue in adults with GWI, improving
           health of affected patients and potentially providing gains to society through reduced
           health care utilization and absenteeism related costs.

        -  Positive biomarker findings would contribute to our better understanding of the etiology
           of CRS and fatigue in the GWI population and of possible biological pathways underlying
           the NI efficacy.

        -  The finding that either form of NI is cost effective would provide economic
           justification for its clinical use.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Sino-Nasal Outcome Test (SNOT-20) Score From Baseline
time frame: Change from baseline week 8, change from baseline week 26
description: Sino-Nasal Outcome Test (SNOT-20) is a recommended tool for clinical trial research involving CRS. Sinus disease specific quality of life will be measured using the total score of this validated 20 item questionnaire. It is a reliable and valid outcome measure for patients with CRS (Cronbach's α 0.9, test-retest r = 0.9) that describes the health burden and is sensitive to clinical change. Patients who are more affected by CRS tend to have greater SNOT-20 scores (P < 0.01). The SNOT-20 score is expected to improve in NI-treated subjects compared to controls. Findings of the PI's prior RCT of adults with CRS are consistent with the above evidence. The total range of possible scores is 0-100. The higher the score, the worse the symptoms.
measure: Change in Multidimensional Fatigue Inventory (MFI) Over Baseline
time frame: Baseline to weeks 8 & 26
description: The Multidimensional Fatigue Inventory is a validated disease specific outcome measure for fatigue. The instrument has good internal consistency (average Cronbach's alpha 0.84). Construct validity was established after comparisons between and within groups, assuming differences in fatigue based on differences in circumstances and/or activity level. Convergent validity was investigated by correlating the MFI-scales with a Visual Analogue Scale measuring fatigue. Fatigue is expected to improve in the NI-treated patients compared to controls. The total range of possible scores is 0-100. The higher the score, the more fatigue.
measure: Change in Medical Outcomes Survey Short Form-36 (SF-36) Over Baseline
time frame: Baseline and weeks 8 & 26
description: SF-36 is a validated questionnaire designed to assess health status, function and overall health related quality of life. The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. Gulf War Illness and chronic rhinosinusitis both affect sleep and breathing parameters. Prior studies suggest that both may be improved with SNI in some subjects. Eighteen relevant sleep and breathing related questions to the SF-36. The total range is 0-100. The lower the score, the more disability.
arm group label: Nasal Irrigation - Saline
arm group type: Experimental
description: nasal irrigation using saline plus routine care for symptoms of CRS and fatigue
arm group label: Nasal Irrigation - Xylitol
arm group type: Experimental
description: Nasal Irrigation with Xylitol plus routine care for symptoms of CRS and fatigue
arm group label: Control Group
arm group type: No Intervention
description: Control group subjects continue to use routine care only
intervention type: Other
intervention name: Nasal Irrigation - Saline
description: Liquid-based nasal irrigation (NI) is performed using a nasal irrigation cup ("neti pot"), a simple hand-held vessel that uses the force of gravity to gently irrigate the user's nasal cavity. Subjects will be requested to perform NI twice daily. The subjects will prepare the saline solution by themselves using the study-provided kit which will include packets of salt powder and the neti pot; subjects will dissolve the powder in lukewarm tap water to achieve a 2% buffered saline solution. The solution is then delivered to the nasal cavity using neti pot.
arm group label: Nasal Irrigation - Saline
other name: 2% buffered saline
intervention type: Drug
intervention name: Nasal Irrigation - Xylitol
description: Liquid-based nasal irrigation (NI) is performed using a nasal irrigation cup ("neti pot"), a simple hand-held vessel that uses the force of gravity to gently irrigate the user's nasal cavity. Subjects will be requested to perform NI twice daily. The subjects will prepare the Xylitol solution by themselves using the study-provided kit which will include packets of Xylitol powder and the neti pot; subjects will dissolve the powder in lukewarm tap water to achieve a 5% Xylitol solution. The solution is then delivered to the nasal cavity using neti pot.
arm group label: Nasal Irrigation - Xylitol
other name: 5% Xylitol solution
criteria: 
gender: All
minimum age: 35 Years
maximum age: 75 Years
healthy volunteers: No
last name: Rachel Molander, MD
role: Principal Investigator
affiliation: US Department of Veterans Affairs, William S. Middleton Memorial Veterans Hospital
last name: David P Rabago, MD
role: Principal Investigator
affiliation: University of Wisconsin, Madison
facility: 
country: United States
responsible party type: Sponsor
mesh term: Sinusitis
mesh term: Fatigue
mesh term: Persian Gulf Syndrome
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 