<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/NCT03303417</url>
  </required_header>
  <id_info>
    <org_study_id>A200317</org_study_id>
    <nct_id>NCT03303417</nct_id>
  </id_info>
  <brief_title>Effect of Kiwifruit on Gastrointestinal Fluid Distribution and Transit in Healthy Volunteers</brief_title>
  <acronym>KIWI</acronym>
  <official_title>Effect of Kiwifruit on Gastrointestinal Fluid Distribution and Transit in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Nottingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Zespri International Limited</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Nottingham</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Constipation is a widespread and common problem in which a person finds it difficult and/or&#xD;
      painful to open their bowels. The current treatment is the use of medications called&#xD;
      laxatives. Kiwifruit is a widely available food that has been shown to possess some laxative&#xD;
      properties. The cause of this is unknown. Non-invasive medical imaging techniques such as&#xD;
      Magnetic Resonance Imaging now allow taking pictures of the gut and its contents. The&#xD;
      Nottingham GI MRI research group specialises in these techniques and in this study use such&#xD;
      images to assess the changes induced in the gut contents by kiwifruit to improve&#xD;
      understanding of how it helps patients with constipation.&#xD;
&#xD;
      The volunteers will be asked to undergo 2 studies in which they take either kiwifruit or&#xD;
      placebo (sugary drink) two times a day for 2 days and then spend a study day where will they&#xD;
      will be fed some more kiwifruit/placebo and some normal food and image their gut at&#xD;
      intervals. Participants will be asked to complete a stool diary to determine if they&#xD;
      experience a laxative effect.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Background. Chronic constipation affects approximately 17% of the population worldwide&#xD;
           and remains an important unmet need since patients are currently often dissatisfied with&#xD;
           treatment Current treatments which stimulate propulsive colonic motility or osmotic&#xD;
           laxatives are successful in increasing stool frequency but are often associated with&#xD;
           bloating, cramps and abdominal discomfort. Furthermore, such powerful treatments taken&#xD;
           intermittently often create abnormal colonic contents and may result in alternation&#xD;
           between diarrhoea and no stools. Many patients would benefit from a less powerful&#xD;
           treatment which could be taken daily. Kiwifruit offer such an alternative and have been&#xD;
           shown to increase stool volume and frequency. The mode of action however is unclear.&#xD;
           Kiwi is 3% fibre (approximately 1/3 insoluble) and contains around 3% nonstarch&#xD;
           polysaccharide including pectins, hemicellulose and cellulose, with high water holding&#xD;
           capacity 1.5 times that of ispaghula, a commonly used laxative. Using recently developed&#xD;
           and validated novel non-invasive MRI techniques, the University can assess transit and&#xD;
           fluid distribution in the small intestine [4]. The University has also developed methods&#xD;
           to assess colonic fluid, volumes and motility.&#xD;
&#xD;
        2. Aims. To assess the effect of kiwifruit on gastrointestinal fluid distribution.&#xD;
&#xD;
        3. Experimental protocol and methods. A randomised, placebo controlled, 2-way cross-over&#xD;
           study in N=15 healthy volunteers assessing the response (versus baseline values) of 2&#xD;
           kiwifruit b.d vs placebo (28 gm maltodextrin drink providing 120kcal equal to that of 2&#xD;
           kiwifruit) daily. After a screening visit to confirm eligibility, study subjects will be&#xD;
           randomised as to the test product schedule. Subjects will complete a daily stool diary&#xD;
           documenting stool frequency and consistency using the Bristol Stool Form Scale. They&#xD;
           will consume the test product allocated starting on Day 4. At 9 am of the morning of Day&#xD;
           5 they will ingest 5 MRI transit markers as described below and note the time of&#xD;
           ingestion. The markers will be imaged at 24 hours (baseline scan of Day 6). On the main&#xD;
           study day, the subjects will arrive fasted overnight and undergo fasting scans before&#xD;
           consuming that day's allocated test product with 250ml of water. After 30 minutes&#xD;
           considered to be Time =0 they will consume a standard rice pudding meal as used in&#xD;
           previous studies. They will then undergo serial scanning hourly for 7 hours taking the&#xD;
           second dose of test product plus 250ml water at Time 180 minutes. The third dose is&#xD;
           taken at 320 minutes followed at 380 minutes by a second, larger test meal consisting of&#xD;
           400 g microwaveable macaroni cheese ready meal (Sainsbury), 100 g cheesecake slice&#xD;
           (Sainsbury), and 250 mL bottled still water. The second test meal provides approx. 1000&#xD;
           kcal. The final scan will at time 420 minutes to assess the effect of ileal emptying on&#xD;
           gastrointestinal fluid distribution. They will then be allowed home. There will be 2&#xD;
           weeks between studies to ensure return to baseline. At the end of the study a further 3&#xD;
           participants will be scanned in exactly the same protocol however at a lower dose of&#xD;
           kiwifruit (2 fruit once daily) to determine if the effect is still visible.&#xD;
&#xD;
        4. Measurable end points/statistical power of the study. Primary endpoint: Effect of&#xD;
           Kiwifruit on Ascending colon T1 area under curve from time 0-420.&#xD;
&#xD;
      Secondary endpoints: Effect of Kiwifruit on the following measures both fasting and&#xD;
      postprandial AUC 0-420 minutes: 1) small bowel water content 2) ascending (AC), transverse&#xD;
      (TC) and descending (DC) colonic volumes. 3) Transit of markers through gut as assessed by&#xD;
      the weighted position score at 24 h (WAPS24) 4) Colonic motility 5) Gastric emptying of test&#xD;
      meal 6) T1 of AC and DC. Pilot data with a standard laxative dose of ispaghula 7g t.d.s.&#xD;
      showed a change of T1 AUC 0-360 of mean (SD) 88 (55) sec.min . Using this data n=15 healthy&#xD;
      volunteers will give us &gt;90% power to detect such a difference.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 27, 2017</start_date>
  <completion_date type="Actual">June 1, 2018</completion_date>
  <primary_completion_date type="Actual">November 1, 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>MRI analysis will be performed blind to the intervention</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Relaxation Time in Ascending Colon</measure>
    <time_frame>0 - 8 hours</time_frame>
    <description>Area under curve of Ascending colon T1 measured on MRI , in milliseconds. Measurements at 0, 1, 2, 3, 4, 5, 6, 7, and 8 hours post-intervention</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Small Bowel Water Content Measured by MRI, in mL</measure>
    <time_frame>0 - 8 hours</time_frame>
    <description>Area under the curve of change of small bowel water, 0-8 hours, measured by MRI, in mL Measurements at 0, 1, 2, 3, 4, 5, 6, 7, and 8 hours post-intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Colonic Volume</measure>
    <time_frame>0 - 8 hours</time_frame>
    <description>Ascending (AC), transverse (TC) and descending (DC) colonic volumes, measured by MRI, in mL Data given: AUC for total colon Measurements at 0, 1, 2, 3, 4, 5, 6, 7, and 8 hours post-intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Colonic Transit Time</measure>
    <time_frame>24hr</time_frame>
    <description>Transit of markers through gut as assessed by the weighted average position score (total score 0-7, calculated from a score of 0-7 of each of the 5 marker pills) at 24 h on MRI A lower score indicates faster transit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bowel Habit</measure>
    <time_frame>7 days</time_frame>
    <description>Assessment, via Diary, of bowel frequency Data given: stool frequency</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Constipation</condition>
  <condition>Diet Modification</condition>
  <arm_group>
    <arm_group_label>Kiwifruit</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants asked to consume 2 kiwifruit twice a day for 3 days before undergoing MRI Scan</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants asked to consume a calorie-matched sugar drink twice a day for 3 days before undergoing MRI Scan</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>MRI Scan</intervention_name>
    <description>Participants will undergo hourly MRI scans on day 3 to assess bowel fluid content</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Kiwifruit</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Kiwifruit</intervention_name>
    <description>Kiwifruit</description>
    <arm_group_label>Kiwifruit</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>calorie-matched sugar drink</intervention_name>
    <description>calorie-matched sugar drink</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy volunteers scoring within the normal range for bowel symptoms as assessed&#xD;
             using the GSRS, aged 18-65 years.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Inability to discontinue medication likely to alter GI transit.&#xD;
&#xD;
          2. Previous gastrointestinal surgery (excluding cholecystectomy and appendectomy).&#xD;
&#xD;
          3. Known inflammatory bowel disease, coeliac disease.&#xD;
&#xD;
          4. Known intolerance of kiwifruit.&#xD;
&#xD;
          5. Inability to discontinue drugs likely to alter gut transit.&#xD;
&#xD;
          6. Subjects considered by the investigator unlikely to comply with study protocol.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Nottingham</name>
      <address>
        <city>Nottingham</city>
        <state>Nottinghamshire</state>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>October 2, 2017</study_first_submitted>
  <study_first_submitted_qc>October 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 6, 2017</study_first_posted>
  <results_first_submitted>October 16, 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>March 18, 2019</last_update_submitted>
  <last_update_submitted_qc>March 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Nottingham</investigator_affiliation>
    <investigator_full_name>Robin Spiller</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Kiwifruit</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Constipation</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 12, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/17/NCT03303417/Prot_SAP_ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>16 healthy volunteers were recruited from the population of Nottingham and surroundings. 2 dropped out after a single visit due to unexpected work commitments so 14 volunteers completed the study</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Kiwifruit Then Control</title>
          <description>Participants asked to consume 2 kiwifruit twice a day for 3 days before undergoing MRI Scan MRI Scan: Participants will undergo hourly MRI scans on day 3 to assess bowel fluid content Kiwifruit: Kiwifruit.&#xD;
Washout period of 2 weeks&#xD;
Then&#xD;
Participants asked to consume a calorie-matched sugar drink twice a day for 3 days before undergoing MRI Scan MRI Scan: Participants will undergo hourly MRI scans on day 3 to assess bowel fluid content calorie-matched sugar drink: calorie-matched sugar drink</description>
        </group>
        <group group_id="P2">
          <title>Control Then Kiwifruit</title>
          <description>Participants asked to consume a calorie-matched sugar drink twice a day for 3 days before undergoing MRI Scan&#xD;
MRI Scan: Participants will undergo hourly MRI scans on day 3 to assess bowel fluid content&#xD;
calorie-matched sugar drink: calorie-matched sugar drink&#xD;
Washout of 2 weeks&#xD;
Then Participants asked to consume 2 kiwifruit twice a day for 3 days before undergoing MRI Scan MRI Scan: Participants will undergo hourly MRI scans on day 3 to assess bowel fluid content Kiwifruit: Kiwifruit</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>14 participants completed the study</population>
      <group_list>
        <group group_id="B1">
          <title>All Study Participants</title>
          <description>All participants randomised to either &quot;Kiwifruit then Control&quot; or &quot;Control then Kiwifruit&quot; Interventions</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="14"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26" lower_limit="21" upper_limit="33"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United Kingdom</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23" lower_limit="17.6" upper_limit="30.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Relaxation Time in Ascending Colon</title>
        <description>Area under curve of Ascending colon T1 measured on MRI , in milliseconds. Measurements at 0, 1, 2, 3, 4, 5, 6, 7, and 8 hours post-intervention</description>
        <time_frame>0 - 8 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Kiwifruit</title>
            <description>Participants asked to consume 2 kiwifruit twice a day for 3 days before undergoing MRI Scan&#xD;
MRI Scan: Participants will undergo hourly MRI scans on day 3 to assess bowel fluid content&#xD;
Kiwifruit: Kiwifruit</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Participants asked to consume a calorie-matched sugar drink twice a day for 3 days before undergoing MRI Scan&#xD;
MRI Scan: Participants will undergo hourly MRI scans on day 3 to assess bowel fluid content&#xD;
calorie-matched sugar drink: calorie-matched sugar drink</description>
          </group>
        </group_list>
        <measure>
          <title>Relaxation Time in Ascending Colon</title>
          <description>Area under curve of Ascending colon T1 measured on MRI , in milliseconds. Measurements at 0, 1, 2, 3, 4, 5, 6, 7, and 8 hours post-intervention</description>
          <units>seconds*minutes</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_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="312" spread="92"/>
                    <measurement group_id="O2" value="256" spread="97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Small Bowel Water Content Measured by MRI, in mL</title>
        <description>Area under the curve of change of small bowel water, 0-8 hours, measured by MRI, in mL Measurements at 0, 1, 2, 3, 4, 5, 6, 7, and 8 hours post-intervention</description>
        <time_frame>0 - 8 hours</time_frame>
        <population>14 participants completed the study</population>
        <group_list>
          <group group_id="O1">
            <title>Kiwifruit</title>
            <description>Participants asked to consume 2 kiwifruit twice a day for 3 days before undergoing MRI Scan&#xD;
MRI Scan: Participants will undergo hourly MRI scans on day 3 to assess bowel fluid content&#xD;
Kiwifruit: Kiwifruit</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Participants asked to consume a calorie-matched sugar drink twice a day for 3 days before undergoing MRI Scan&#xD;
MRI Scan: Participants will undergo hourly MRI scans on day 3 to assess bowel fluid content&#xD;
calorie-matched sugar drink: calorie-matched sugar drink</description>
          </group>
        </group_list>
        <measure>
          <title>Small Bowel Water Content Measured by MRI, in mL</title>
          <description>Area under the curve of change of small bowel water, 0-8 hours, measured by MRI, in mL Measurements at 0, 1, 2, 3, 4, 5, 6, 7, and 8 hours post-intervention</description>
          <population>14 participants completed the study</population>
          <units>ml*minutes</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_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85530" spread="34923"/>
                    <measurement group_id="O2" value="35023" spread="15557"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Colonic Volume</title>
        <description>Ascending (AC), transverse (TC) and descending (DC) colonic volumes, measured by MRI, in mL Data given: AUC for total colon Measurements at 0, 1, 2, 3, 4, 5, 6, 7, and 8 hours post-intervention</description>
        <time_frame>0 - 8 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Kiwifruit</title>
            <description>Participants asked to consume 2 kiwifruit twice a day for 3 days before undergoing MRI Scan&#xD;
MRI Scan: Participants will undergo hourly MRI scans on day 3 to assess bowel fluid content&#xD;
Kiwifruit: Kiwifruit</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Participants asked to consume a calorie-matched sugar drink twice a day for 3 days before undergoing MRI Scan&#xD;
MRI Scan: Participants will undergo hourly MRI scans on day 3 to assess bowel fluid content&#xD;
calorie-matched sugar drink: calorie-matched sugar drink</description>
          </group>
        </group_list>
        <measure>
          <title>Colonic Volume</title>
          <description>Ascending (AC), transverse (TC) and descending (DC) colonic volumes, measured by MRI, in mL Data given: AUC for total colon Measurements at 0, 1, 2, 3, 4, 5, 6, 7, and 8 hours post-intervention</description>
          <units>ml*minutes</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_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="283583" spread="59402"/>
                    <measurement group_id="O2" value="243182" spread="46682"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Colonic Transit Time</title>
        <description>Transit of markers through gut as assessed by the weighted average position score (total score 0-7, calculated from a score of 0-7 of each of the 5 marker pills) at 24 h on MRI A lower score indicates faster transit.</description>
        <time_frame>24hr</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Kiwifruit</title>
            <description>Participants asked to consume 2 kiwifruit twice a day for 3 days before undergoing MRI Scan&#xD;
MRI Scan: Participants will undergo hourly MRI scans on day 3 to assess bowel fluid content&#xD;
Kiwifruit: Kiwifruit</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Participants asked to consume a calorie-matched sugar drink twice a day for 3 days before undergoing MRI Scan&#xD;
MRI Scan: Participants will undergo hourly MRI scans on day 3 to assess bowel fluid content&#xD;
calorie-matched sugar drink: calorie-matched sugar drink</description>
          </group>
        </group_list>
        <measure>
          <title>Colonic Transit Time</title>
          <description>Transit of markers through gut as assessed by the weighted average position score (total score 0-7, calculated from a score of 0-7 of each of the 5 marker pills) at 24 h on MRI A lower score indicates faster transit.</description>
          <units>Score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</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_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8" lower_limit="0" upper_limit="1.4"/>
                    <measurement group_id="O2" value="1.0" lower_limit="0.5" upper_limit="3.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Bowel Habit</title>
        <description>Assessment, via Diary, of bowel frequency Data given: stool frequency</description>
        <time_frame>7 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Kiwifruit</title>
            <description>Participants asked to consume 2 kiwifruit twice a day for 3 days before undergoing MRI Scan&#xD;
MRI Scan: Participants will undergo hourly MRI scans on day 3 to assess bowel fluid content&#xD;
Kiwifruit: Kiwifruit</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Participants asked to consume a calorie-matched sugar drink twice a day for 3 days before undergoing MRI Scan&#xD;
MRI Scan: Participants will undergo hourly MRI scans on day 3 to assess bowel fluid content&#xD;
calorie-matched sugar drink: calorie-matched sugar drink</description>
          </group>
        </group_list>
        <measure>
          <title>Bowel Habit</title>
          <description>Assessment, via Diary, of bowel frequency Data given: stool frequency</description>
          <units>stools per day</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_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.46" spread="0.66"/>
                    <measurement group_id="O2" value="1.14" spread="0.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>4 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Kiwifruit</title>
          <description>Participants asked to consume 2 kiwifruit twice a day for 3 days before undergoing MRI Scan&#xD;
MRI Scan: Participants will undergo hourly MRI scans on day 3 to assess bowel fluid content&#xD;
Kiwifruit: Kiwifruit</description>
        </group>
        <group group_id="E2">
          <title>Control</title>
          <description>Participants asked to consume a calorie-matched sugar drink twice a day for 3 days before undergoing MRI Scan&#xD;
MRI Scan: Participants will undergo hourly MRI scans on day 3 to assess bowel fluid content&#xD;
calorie-matched sugar drink: calorie-matched sugar drink</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"/>
              </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"/>
              </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"/>
              </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>
    <limitations_and_caveats>This mechanistic study was limited by small sample size which was exacerbated by some participants' withdrawal from the study.&#xD;
Did not control any other aspects of diet</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Robin Spiller</name_or_title>
      <organization>University of Nottingham</organization>
      <phone>0115 823 1090</phone>
      <email>robin.spiller@nottingham.ac.uk</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/NCT03303417
org study id: A200317
nct id: NCT03303417
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Constipation is a widespread and common problem in which a person finds it difficult and/or
      painful to open their bowels. The current treatment is the use of medications called
      laxatives. Kiwifruit is a widely available food that has been shown to possess some laxative
      properties. The cause of this is unknown. Non-invasive medical imaging techniques such as
      Magnetic Resonance Imaging now allow taking pictures of the gut and its contents. The
      Nottingham GI MRI research group specialises in these techniques and in this study use such
      images to assess the changes induced in the gut contents by kiwifruit to improve
      understanding of how it helps patients with constipation.

      The volunteers will be asked to undergo 2 studies in which they take either kiwifruit or
      placebo (sugary drink) two times a day for 2 days and then spend a study day where will they
      will be fed some more kiwifruit/placebo and some normal food and image their gut at
      intervals. Participants will be asked to complete a stool diary to determine if they
      experience a laxative effect.
1. Background. Chronic constipation affects approximately 17% of the population worldwide
           and remains an important unmet need since patients are currently often dissatisfied with
           treatment Current treatments which stimulate propulsive colonic motility or osmotic
           laxatives are successful in increasing stool frequency but are often associated with
           bloating, cramps and abdominal discomfort. Furthermore, such powerful treatments taken
           intermittently often create abnormal colonic contents and may result in alternation
           between diarrhoea and no stools. Many patients would benefit from a less powerful
           treatment which could be taken daily. Kiwifruit offer such an alternative and have been
           shown to increase stool volume and frequency. The mode of action however is unclear.
           Kiwi is 3% fibre (approximately 1/3 insoluble) and contains around 3% nonstarch
           polysaccharide including pectins, hemicellulose and cellulose, with high water holding
           capacity 1.5 times that of ispaghula, a commonly used laxative. Using recently developed
           and validated novel non-invasive MRI techniques, the University can assess transit and
           fluid distribution in the small intestine [4]. The University has also developed methods
           to assess colonic fluid, volumes and motility.

        2. Aims. To assess the effect of kiwifruit on gastrointestinal fluid distribution.

        3. Experimental protocol and methods. A randomised, placebo controlled, 2-way cross-over
           study in N=15 healthy volunteers assessing the response (versus baseline values) of 2
           kiwifruit b.d vs placebo (28 gm maltodextrin drink providing 120kcal equal to that of 2
           kiwifruit) daily. After a screening visit to confirm eligibility, study subjects will be
           randomised as to the test product schedule. Subjects will complete a daily stool diary
           documenting stool frequency and consistency using the Bristol Stool Form Scale. They
           will consume the test product allocated starting on Day 4. At 9 am of the morning of Day
           5 they will ingest 5 MRI transit markers as described below and note the time of
           ingestion. The markers will be imaged at 24 hours (baseline scan of Day 6). On the main
           study day, the subjects will arrive fasted overnight and undergo fasting scans before
           consuming that day's allocated test product with 250ml of water. After 30 minutes
           considered to be Time =0 they will consume a standard rice pudding meal as used in
           previous studies. They will then undergo serial scanning hourly for 7 hours taking the
           second dose of test product plus 250ml water at Time 180 minutes. The third dose is
           taken at 320 minutes followed at 380 minutes by a second, larger test meal consisting of
           400 g microwaveable macaroni cheese ready meal (Sainsbury), 100 g cheesecake slice
           (Sainsbury), and 250 mL bottled still water. The second test meal provides approx. 1000
           kcal. The final scan will at time 420 minutes to assess the effect of ileal emptying on
           gastrointestinal fluid distribution. They will then be allowed home. There will be 2
           weeks between studies to ensure return to baseline. At the end of the study a further 3
           participants will be scanned in exactly the same protocol however at a lower dose of
           kiwifruit (2 fruit once daily) to determine if the effect is still visible.

        4. Measurable end points/statistical power of the study. Primary endpoint: Effect of
           Kiwifruit on Ascending colon T1 area under curve from time 0-420.

      Secondary endpoints: Effect of Kiwifruit on the following measures both fasting and
      postprandial AUC 0-420 minutes: 1) small bowel water content 2) ascending (AC), transverse
      (TC) and descending (DC) colonic volumes. 3) Transit of markers through gut as assessed by
      the weighted position score at 24 h (WAPS24) 4) Colonic motility 5) Gastric emptying of test
      meal 6) T1 of AC and DC. Pilot data with a standard laxative dose of ispaghula 7g t.d.s.
      showed a change of T1 AUC 0-360 of mean (SD) 88 (55) sec.min . Using this data n=15 healthy
      volunteers will give us >90% power to detect such a difference.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Single (Outcomes Assessor)
masking description: MRI analysis will be performed blind to the intervention
measure: Relaxation Time in Ascending Colon
time frame: 0 - 8 hours
description: Area under curve of Ascending colon T1 measured on MRI , in milliseconds. Measurements at 0, 1, 2, 3, 4, 5, 6, 7, and 8 hours post-intervention
measure: Small Bowel Water Content Measured by MRI, in mL
time frame: 0 - 8 hours
description: Area under the curve of change of small bowel water, 0-8 hours, measured by MRI, in mL Measurements at 0, 1, 2, 3, 4, 5, 6, 7, and 8 hours post-intervention
measure: Colonic Volume
time frame: 0 - 8 hours
description: Ascending (AC), transverse (TC) and descending (DC) colonic volumes, measured by MRI, in mL Data given: AUC for total colon Measurements at 0, 1, 2, 3, 4, 5, 6, 7, and 8 hours post-intervention
measure: Colonic Transit Time
time frame: 24hr
description: Transit of markers through gut as assessed by the weighted average position score (total score 0-7, calculated from a score of 0-7 of each of the 5 marker pills) at 24 h on MRI A lower score indicates faster transit.
measure: Bowel Habit
time frame: 7 days
description: Assessment, via Diary, of bowel frequency Data given: stool frequency
arm group label: Kiwifruit
arm group type: Experimental
description: Participants asked to consume 2 kiwifruit twice a day for 3 days before undergoing MRI Scan
arm group label: Control
arm group type: Placebo Comparator
description: Participants asked to consume a calorie-matched sugar drink twice a day for 3 days before undergoing MRI Scan
intervention type: Diagnostic Test
intervention name: MRI Scan
description: Participants will undergo hourly MRI scans on day 3 to assess bowel fluid content
arm group label: Control
arm group label: Kiwifruit
intervention type: Other
intervention name: Kiwifruit
description: Kiwifruit
arm group label: Kiwifruit
intervention type: Other
intervention name: calorie-matched sugar drink
description: calorie-matched sugar drink
arm group label: Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: University of Nottingham
investigator full name: Robin Spiller
investigator title: Professor
mesh term: Constipation
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: This mechanistic study was limited by small sample size which was exacerbated by some participants' withdrawal from the study.
Did not control any other aspects of diet
point of contact: 