<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/NCT03833999</url>
  </required_header>
  <id_info>
    <org_study_id>85-1807</org_study_id>
    <nct_id>NCT03833999</nct_id>
  </id_info>
  <brief_title>Mode of Action of Ondansetron, a 5-HT Receptor 3 Antagonist, in Lactulose Induced Diarrhoea</brief_title>
  <acronym>MOLID</acronym>
  <official_title>Mode of Action of Ondansetron, a 5-HT Receptor 3 Antagonist, in Lactulose Induced Diarrhoea</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Nottingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a double-blind, two period, two treatment crossover trial of ondansetron verses&#xD;
      placebo studying the effects of ondansetron in the small and large bowel, specifically its&#xD;
      effects on the amount of water in the gut, measured by MRI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      If participants interested to take part the investigators will ask some questions to check&#xD;
      participants are eligible to take part. Part of this involves measuring height, weight and&#xD;
      having an electrocardiogram (ECG) to assess the heart. This is non-invasive and is achieved&#xD;
      by attaching stickers across participants' chest. If participants are eligible the&#xD;
      investigators will invite them to join the study, asked to sign a consent form and arrange&#xD;
      for them to come to 4 study days.&#xD;
&#xD;
      Study Days The study days take place at the 3T Acheiva MRI scanner at the Sir Peter Mansfield&#xD;
      Imaging Centre. This is located on the University Park campus.&#xD;
&#xD;
      The day before each scanning day participants will be asked to eat and drink as normal,&#xD;
      avoiding beans or pulses and abstain from alcohol. The investigators ask that participants&#xD;
      avoid strenuous exercise, and if they smoke to continue as normal.&#xD;
&#xD;
      On the morning of the day 1 of the study participants should come to the MRI scanner around 8&#xD;
      o'clock in the morning. They should not have anything to eat or drink at all, unless they&#xD;
      need a sip of water to swallow essential medicines. The investigators will confirm that it is&#xD;
      still safe for participants to be scanned and participants will then change into surgical&#xD;
      scrubs (provided) to begin the study.&#xD;
&#xD;
      Participants will be randomly assigned to take either ondansetron, the anti-sickness tablet,&#xD;
      for the first 2 visits or a dummy tablet (placebo) three times daily. They will be overcoated&#xD;
      tablets so that neither participants nor the research team can tell which one it is.&#xD;
&#xD;
      Participants will then have an MRI scan, during which the investigators will scan the body in&#xD;
      different ways. A separate information sheet tells participants more about this.&#xD;
&#xD;
      After these are done the investigators will give participants a meal supplement drink called&#xD;
      Fortisip. Participants will have around 10 minutes to finish the drink. As soon as&#xD;
      participants finish the MRI will be repeated. Participants will then have 3 further MRI&#xD;
      scans, 2, 4 and 6 hours after the meal. After the last scan the investigators will give&#xD;
      participants another dose of either the ondansetron or the placebo, and 20mls of a laxative&#xD;
      called lactulose. The investigators will provide participants with tablets and the laxative&#xD;
      for the following day at home.&#xD;
&#xD;
      Day 2 of the study participants can have a normal day at home, however the investigators ask&#xD;
      that participants refrain from strenuous exercise, avoid alcohol, beans and pulses and&#xD;
      continue a usual smoking habit if applicable. Participants are asked to take the tablet&#xD;
      (either ondansetron or placebo) three times a day (in the morning, midday and evening) and&#xD;
      20mls of the laxative in the morning and evening. They are also asked to take 5 MRI marker&#xD;
      tablets at 8pm, and take a timestamped photo or video so the investigators can ensure these&#xD;
      are taken at the correct time. The marker tablets will be used to measure the speed of food&#xD;
      along the gut on the scan on day 3.&#xD;
&#xD;
      On day 3 participants are asked to return for another day of scanning at the Sir Peter&#xD;
      Mansfield Imagine Centre. Again, participants should come to the MRI scanner around 8 o'clock&#xD;
      in the morning. They should not have anything to eat or drink at all, unless a sip of water&#xD;
      is needed to swallow essential medicines. The investigators will re-confirm that it is still&#xD;
      safe for participants to be scanned and participants will then change into surgical scrubs&#xD;
      (provided) to begin the study.&#xD;
&#xD;
      Participants will receive a further dose of the ondansetron or placebo tablet, then have an&#xD;
      MRI scan before drinking the same Fortisip meal supplement and the lactulose. Once&#xD;
      participants have finished the drink they will have 2 further MRI scans, 2 and 4 hours after&#xD;
      the meal. Participants can then leave for the day.&#xD;
&#xD;
      The investigators ask that participants come back to repeat the above 3 day procedure once&#xD;
      more, taking the alternative tablet the second time around. Study periods will normally be&#xD;
      one week apart. It is very important that participants attend both study periods as the&#xD;
      investigators will compare the results from one week to the other.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 16, 2018</start_date>
  <completion_date type="Actual">June 27, 2019</completion_date>
  <primary_completion_date type="Actual">June 27, 2019</primary_completion_date>
  <phase>Phase 4</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>
    <intervention_model_description>double-blind, two-period, two-treatment crossover trial</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Double blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>small bowel water content</measure>
    <time_frame>0-6 hours post meal</time_frame>
    <description>Change from baseline in area under the curve (AUC) small bowel water content</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>small bowel motility (global motility score, arbitrary units)</measure>
    <time_frame>2 and 4 hours postprandially</time_frame>
    <description>Change from baseline motility over the study using cine MRI. An increased value indicates increased small bowel motility</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weighted average position score (WAPS)</measure>
    <time_frame>baseline on day 3</time_frame>
    <description>MRI method of assessing colonic transit using MR marker pills ingested 12 hours before the scan. A lower value indicates faster whole gut transit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T1 of the ascending colon (T1AC)</measure>
    <time_frame>baseline on day 3</time_frame>
    <description>MRI measure of water content in the ascending colon.Change from baseline in AUC T1AC from 0-4 hours. A higher value indicates more watery ascending colon content.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Motility Disorder of Intestine</condition>
  <condition>Ondansetron</condition>
  <condition>Small Bowel Water</condition>
  <arm_group>
    <arm_group_label>Ondansetron and lactulose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ondansetron 8mg three times daily for 48 hours lactulose 20ml twice daily for 48 hours Serial abdominal MRI imaging</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo and lactulose</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>placebo oral capsule, one three times daily for 48 hours lactulose 20ml twice daily for 48 hours Serial abdominal MRI imaging</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ondansetron 8mg</intervention_name>
    <description>ondansetron, a 5HT3 receptor antagonist used clinically in nausea and vomiting</description>
    <arm_group_label>Ondansetron and lactulose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>abdominal MRI</intervention_name>
    <description>serial MRIs on day 1 and day 3 of the study, at baseline and 2 hours apart 0-6 hours after meal ingestion on day 1 and 0-4 hours after the meal on day 3</description>
    <arm_group_label>Ondansetron and lactulose</arm_group_label>
    <arm_group_label>Placebo and lactulose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lactulose</intervention_name>
    <description>Participants will receive 20mls lactulose twice daily for 48 hours prior to the third study day</description>
    <arm_group_label>Ondansetron and lactulose</arm_group_label>
    <arm_group_label>Placebo and lactulose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral capsule</intervention_name>
    <description>overcoated placebo tablet, identical to the ondansetron</description>
    <arm_group_label>Placebo and lactulose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  aged 18 or older&#xD;
&#xD;
          -  able to give informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy declared by candidate&#xD;
&#xD;
          -  History declared by the candidate of pre-existing gastrointestinal disorder that may&#xD;
             affect bowel function, congenital long QT syndrome or QTc &gt;450msecs for males or 470&#xD;
             msecs for female on screening ECG.&#xD;
&#xD;
          -  A positive diagnosis of irritable bowel syndrome based on the Rome IV criteria&#xD;
             questionnaire&#xD;
&#xD;
          -  Reported history of previous resection of the oesophagus, stomach or intestine&#xD;
             (excluding appendix)&#xD;
&#xD;
          -  Intestinal stoma&#xD;
&#xD;
          -  Any medical condition making participation potentially compromising participation in&#xD;
             the study e.g. diabetes mellitus, respiratory disease limiting ability to lie in the&#xD;
             scanner, known allergy to one of the food products&#xD;
&#xD;
          -  Contraindications for MRI scanning i.e. metallic implants, pacemakers, history of&#xD;
             metallic foreign body in eye(s) and penetrating eye injury&#xD;
&#xD;
          -  Will not agree to dietary restrictions required during the MRI study day&#xD;
&#xD;
          -  Unable to stop drugs known to alter GI motility including mebeverine, opiates,&#xD;
             monoamine oxidase inhibitors, phenothiazines, benzodiazepines, calcium channel&#xD;
             antagonists for the duration of the study (Selective serotonin reuptake inhibitors and&#xD;
             low dose tricyclic antidepressants will be recorded but will not be an exclusion&#xD;
             criteria)&#xD;
&#xD;
          -  Inability to lie flat or exceed scanner limits of weight &lt;120kg&#xD;
&#xD;
          -  Poor understanding of English language&#xD;
&#xD;
          -  Participation in night shift work the week prior to the study day. Night work is&#xD;
             defined as working between midnight and 6.00 AM&#xD;
&#xD;
          -  Participation in any medical trials for the past 3 months&#xD;
&#xD;
          -  Anyone who in the opinion of the investigator is unlikely to be able to comply with&#xD;
             the protocol e.g. cognitive dysfunction, chaotic lifestyle related to substance abuse&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Robin Spiller</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Nottingham</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Nottingham</name>
      <address>
        <city>Nottingham</city>
        <state>Nottinghamshire</state>
        <zip>NG7 2UH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>January 7, 2019</study_first_submitted>
  <study_first_submitted_qc>February 5, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 7, 2019</study_first_posted>
  <last_update_submitted>November 26, 2019</last_update_submitted>
  <last_update_submitted_qc>November 26, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 27, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ondansetron</keyword>
  <keyword>small bowel water</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Intestinal Diseases</mesh_term>
    <mesh_term>Diarrhea</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ondansetron</mesh_term>
    <mesh_term>Lactulose</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No plans for sharing IPD</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03833999
org study id: 85-1807
nct id: NCT03833999
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a double-blind, two period, two treatment crossover trial of ondansetron verses
      placebo studying the effects of ondansetron in the small and large bowel, specifically its
      effects on the amount of water in the gut, measured by MRI.
If participants interested to take part the investigators will ask some questions to check
      participants are eligible to take part. Part of this involves measuring height, weight and
      having an electrocardiogram (ECG) to assess the heart. This is non-invasive and is achieved
      by attaching stickers across participants' chest. If participants are eligible the
      investigators will invite them to join the study, asked to sign a consent form and arrange
      for them to come to 4 study days.

      Study Days The study days take place at the 3T Acheiva MRI scanner at the Sir Peter Mansfield
      Imaging Centre. This is located on the University Park campus.

      The day before each scanning day participants will be asked to eat and drink as normal,
      avoiding beans or pulses and abstain from alcohol. The investigators ask that participants
      avoid strenuous exercise, and if they smoke to continue as normal.

      On the morning of the day 1 of the study participants should come to the MRI scanner around 8
      o'clock in the morning. They should not have anything to eat or drink at all, unless they
      need a sip of water to swallow essential medicines. The investigators will confirm that it is
      still safe for participants to be scanned and participants will then change into surgical
      scrubs (provided) to begin the study.

      Participants will be randomly assigned to take either ondansetron, the anti-sickness tablet,
      for the first 2 visits or a dummy tablet (placebo) three times daily. They will be overcoated
      tablets so that neither participants nor the research team can tell which one it is.

      Participants will then have an MRI scan, during which the investigators will scan the body in
      different ways. A separate information sheet tells participants more about this.

      After these are done the investigators will give participants a meal supplement drink called
      Fortisip. Participants will have around 10 minutes to finish the drink. As soon as
      participants finish the MRI will be repeated. Participants will then have 3 further MRI
      scans, 2, 4 and 6 hours after the meal. After the last scan the investigators will give
      participants another dose of either the ondansetron or the placebo, and 20mls of a laxative
      called lactulose. The investigators will provide participants with tablets and the laxative
      for the following day at home.

      Day 2 of the study participants can have a normal day at home, however the investigators ask
      that participants refrain from strenuous exercise, avoid alcohol, beans and pulses and
      continue a usual smoking habit if applicable. Participants are asked to take the tablet
      (either ondansetron or placebo) three times a day (in the morning, midday and evening) and
      20mls of the laxative in the morning and evening. They are also asked to take 5 MRI marker
      tablets at 8pm, and take a timestamped photo or video so the investigators can ensure these
      are taken at the correct time. The marker tablets will be used to measure the speed of food
      along the gut on the scan on day 3.

      On day 3 participants are asked to return for another day of scanning at the Sir Peter
      Mansfield Imagine Centre. Again, participants should come to the MRI scanner around 8 o'clock
      in the morning. They should not have anything to eat or drink at all, unless a sip of water
      is needed to swallow essential medicines. The investigators will re-confirm that it is still
      safe for participants to be scanned and participants will then change into surgical scrubs
      (provided) to begin the study.

      Participants will receive a further dose of the ondansetron or placebo tablet, then have an
      MRI scan before drinking the same Fortisip meal supplement and the lactulose. Once
      participants have finished the drink they will have 2 further MRI scans, 2 and 4 hours after
      the meal. Participants can then leave for the day.

      The investigators ask that participants come back to repeat the above 3 day procedure once
      more, taking the alternative tablet the second time around. Study periods will normally be
      one week apart. It is very important that participants attend both study periods as the
      investigators will compare the results from one week to the other.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: double-blind, two-period, two-treatment crossover trial
primary purpose: Basic Science
masking: Double (Participant, Investigator)
masking description: Double blind
measure: small bowel water content
time frame: 0-6 hours post meal
description: Change from baseline in area under the curve (AUC) small bowel water content
measure: small bowel motility (global motility score, arbitrary units)
time frame: 2 and 4 hours postprandially
description: Change from baseline motility over the study using cine MRI. An increased value indicates increased small bowel motility
measure: Weighted average position score (WAPS)
time frame: baseline on day 3
description: MRI method of assessing colonic transit using MR marker pills ingested 12 hours before the scan. A lower value indicates faster whole gut transit
measure: T1 of the ascending colon (T1AC)
time frame: baseline on day 3
description: MRI measure of water content in the ascending colon.Change from baseline in AUC T1AC from 0-4 hours. A higher value indicates more watery ascending colon content.
arm group label: Ondansetron and lactulose
arm group type: Experimental
description: Ondansetron 8mg three times daily for 48 hours lactulose 20ml twice daily for 48 hours Serial abdominal MRI imaging
arm group label: Placebo and lactulose
arm group type: Placebo Comparator
description: placebo oral capsule, one three times daily for 48 hours lactulose 20ml twice daily for 48 hours Serial abdominal MRI imaging
intervention type: Drug
intervention name: Ondansetron 8mg
description: ondansetron, a 5HT3 receptor antagonist used clinically in nausea and vomiting
arm group label: Ondansetron and lactulose
intervention type: Diagnostic Test
intervention name: abdominal MRI
description: serial MRIs on day 1 and day 3 of the study, at baseline and 2 hours apart 0-6 hours after meal ingestion on day 1 and 0-4 hours after the meal on day 3
arm group label: Ondansetron and lactulose
arm group label: Placebo and lactulose
intervention type: Drug
intervention name: Lactulose
description: Participants will receive 20mls lactulose twice daily for 48 hours prior to the third study day
arm group label: Ondansetron and lactulose
arm group label: Placebo and lactulose
intervention type: Drug
intervention name: Placebo oral capsule
description: overcoated placebo tablet, identical to the ondansetron
arm group label: Placebo and lactulose
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Robin Spiller
role: Principal Investigator
affiliation: University of Nottingham
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Intestinal Diseases
mesh term: Diarrhea
mesh term: Ondansetron
mesh term: Lactulose
sharing ipd: No
ipd description: No plans for sharing IPD