<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/NCT03245645</url>
  </required_header>
  <id_info>
    <org_study_id>16-000934</org_study_id>
    <nct_id>NCT03245645</nct_id>
  </id_info>
  <brief_title>FODMAP Reintroduction in Irritable Bowel Syndrome</brief_title>
  <official_title>FODMAP Reintroduction in Irritable Bowel Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, Los Angeles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of California, Los Angeles</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>
      The purpose of this study is to determine the amount and timing of when certain Fermentable&#xD;
      Oligo-Di-Monosaccharides and Polyols (FODMAPs), specifically fructose, can be safely&#xD;
      reintroduced into the diet of Irritable Bowel Syndrome (IBS) patients that have successfully&#xD;
      completed a low-FODMAP elimination diet. The FODMAP diet is an effective treatment for IBS;&#xD;
      however it is unclear how patients can successfully reintroduce and liberalize fructose into&#xD;
      their diet. The low FODMAP diet is thought to reduce IBS symptoms by decreasing water content&#xD;
      and gas production in the bowel and also possibly by altering gut bacteria. Although use of&#xD;
      the FODMAP elimination diet can initially successfully treat IBS symptoms for up to 50-75% of&#xD;
      patients, the reintroduction diet is difficult for patients to complete and maintain for long&#xD;
      periods of time because current methods for reintroduction of FODMAPs are imprecise leading&#xD;
      to frequent recurrent symptoms. As a result, patients often continue the low FODMAP&#xD;
      elimination diet for additional months because they have difficulties knowing how to add back&#xD;
      FODMAPs into their diet. There are no studies to date to help guide patients with FODMAP&#xD;
      reintroduction.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Research supports clinical experience that ingestion of food often triggers the emergence or&#xD;
      exacerbation of symptoms in the majority of patients with irritable bowel syndrome (IBS).&#xD;
      While IBS remains primarily a symptom driven entity, our understanding of its pathophysiology&#xD;
      is evolving. However, comparatively little research has focused on the specific role of&#xD;
      certain foods and how they prompt the development of IBS symptoms.&#xD;
&#xD;
      Food may be linked to changes in motility, visceral sensation, gut microbiome, intestinal&#xD;
      permeability, immune activation and brain-gut axis. This study will focus on fructose, which&#xD;
      is one of the main components of FODMAP (fermentable oligosaccharides, disacharides,&#xD;
      mono-saccharides and polyols) foods. Fructose is a common part of the Western diet and can be&#xD;
      consumed as a free monosaccharide, part of sucrose, or in polymers referred to as fructans.&#xD;
      There are no human gut specific fructose transporters. Rather glucose transporters are used&#xD;
      (GLUT 2,5) leading some to hypothesize that over ingestion of these agents may trigger some&#xD;
      of the enteric complaints of patients with IBS. The literature on fructose malabsorption&#xD;
      gives varying threshold amounts: from 15 to 50 grams in healthy controls, and from 5 to 50&#xD;
      grams in IBS patients/known malabsorbers (Barrett, 2007; Rao, 2007; Frieling, 2011). Average&#xD;
      daily fructose consumption in the American diet is approximately 34 grams, with a range of 15&#xD;
      to 54 grams, which falls well within the threshold levels (Frieling, 2011). FODMAP foods are&#xD;
      thought to induce gastrointestinal symptoms including gas, bloating, abdominal pain or&#xD;
      discomfort, and loose stools by increasing small bowel water content and increasing gas&#xD;
      production by fermentation of foods by gut bacteria. Studies including a recent controlled&#xD;
      clinical trial demonstrated that a low FODMAP diet can be an effective nutritional therapy.&#xD;
&#xD;
      There are risks to prolonged use of a low FODMAPs diet. A study from 2012 suggested that&#xD;
      continued restriction of FODMAPS (longer than 4 weeks) can lead to reduction of luminal&#xD;
      bifidobacteria in patients with IBS. Bifidobacteria mainly inhabit the large intestine where&#xD;
      they produce short chain fatty acids (SCFA) as byproducts, including butyrate, shown to be&#xD;
      important for colorectal cancer prevention and limit enteropathogenic colonization.&#xD;
      Furthermore the diet is very restrictive and difficult for patients to maintain over time.&#xD;
&#xD;
      However, important clinical questions include when FODMAPS can be safely reintroduced into&#xD;
      the diet, how quickly this can be accomplished, and what is a daily threshold of intake that&#xD;
      is acceptable for IBS patients who respond or do not respond to a low FODMAPs diet. There are&#xD;
      no evidence based answers to these questions, and it is in this setting that we propose our&#xD;
      current project.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 24, 2017</start_date>
  <completion_date type="Actual">June 30, 2023</completion_date>
  <primary_completion_date type="Actual">June 30, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adequate relief of IBS symptoms in past 7 days</measure>
    <time_frame>Baseline, 4 weeks (post-elimination diet)</time_frame>
    <description>As indicated by the study coordinator asking the participant &quot;Have you had adequate relief of your IBS symptoms in the past 7 days?&quot;</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Highest amount of grams of sugar in solutions that do not significantly increase IBS symptoms</measure>
    <time_frame>Daily, during weeks 5-7 (reintroduction phase)</time_frame>
    <description>As measured by 100 MM Visual Analog Scale (VAS) with 0 representing no symptoms for overall gastrointestinal symptoms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in IBS-symptom severity scale</measure>
    <time_frame>Baseline, 4 weeks (post-elimination diet), 7 weeks (post-reintroduction phase)</time_frame>
    <description>This is a validated symptom questionnaire pertaining to irritable bowel syndrome symptoms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Visceral Sensitivity Index (VSI)</measure>
    <time_frame>Baseline, 4 weeks (post-elimination diet), 7 weeks (post-reintroduction phase)</time_frame>
    <description>This is a self-report measure of the gastrointestinal symptom-specific anxiety (GSA) of patients with irritable bowel syndrome (IBS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Personal Health Questionnaire (PHQ-15)</measure>
    <time_frame>Baseline, 4 weeks (post-elimination diet), 7 weeks (post-reintroduction phase)</time_frame>
    <description>This is a validated symptom questionnaire pertaining to somatic symptoms severity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in abdominal pain severity</measure>
    <time_frame>Baseline, 4 weeks (post-elimination diet), 7 weeks (post-reintroduction phase)</time_frame>
    <description>This is a self-report measure of the severity of abdominal pain during the week before report gathered by circling a number from 0-20 with 20 being the most intense pain imaginable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in overall severity of gastrointestinal symptoms</measure>
    <time_frame>Baseline, 4 weeks (post-elimination diet), 7 weeks (post-reintroduction phase)</time_frame>
    <description>This is a self-report measure of the overall severity of gastrointestinal symptoms during the week before report gathered by circling a number from 0-20 with 20 being the most intense symptoms imaginable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in severity of the sensation of bloating, abdominal fullness or visible distension</measure>
    <time_frame>Baseline, 4 weeks (post-elimination diet), 7 weeks (post-reintroduction phase)</time_frame>
    <description>This is a self-report measure of the severity of the sensation of bloating, abdominal fullness, or visible distension in the patient's belly that the patient has experienced during the week before report gathered by circling a number from 0-20 with 20 being the most intense sensation imaginable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in intestinal microbiota</measure>
    <time_frame>Baseline, 4 weeks (post-elimination diet)</time_frame>
    <description>This is a measure of the intestinal microbiota 16S rRNA gene signatures in the patients' stool before and after the low FODMAP diet.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in visceral sensitivity index score</measure>
    <time_frame>Baseline, 4 weeks (post-elimination diet), 7 weeks (post-reintroduction phase)</time_frame>
    <description>This is a validated symptom questionnaire pertaining to gastrointestinal symptom related anxiety in patients with irritable bowel syndrome.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Irritable Bowel Syndrome With Diarrhea</condition>
  <condition>Irritable Bowel Syndrome With Mixed Bowel Habits</condition>
  <arm_group>
    <arm_group_label>100% Fructose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The fructose group will help to determine whether an absolute amount of fructose will lead to IBS symptoms.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>100% Glucose</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The glucose group will serve as a control since glucose is not a FODMAP and as a result is not expected to lead to recurrent symptoms.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fructose and Glucose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The glucose/fructose mixture group is a cross comparison group that will determine whether the relative excess fructose concentration is an important cause of IBS symptoms.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Dietary Intervention</intervention_name>
    <description>Food may be linked to changes in motility, visceral sensation, gut microbiome, intestinal permeability, immune activation and brain-gut axis. This study will focus on fructose, which is one of the main components of FODMAP (Fermentable oligosaccharides, dissacharides, mono-saccharides and polyols) foods. Fructose is a common part of the Western diet and can be consumed as a free monosaccharide, part of sucrose, or in polymers referred to as fructans. FODMAP foods are thought to induce gastrointestinal symptoms including gas, bloating, abdominal pain or discomfort, and loose stools by increasing small bowel water content and increasing gas production by fermentation of foods by gut bacteria. Studies including a recent controlled clinical trial demonstrated that a low FODMAP diet can be an effective nutritional therapy.</description>
    <arm_group_label>100% Fructose</arm_group_label>
    <arm_group_label>100% Glucose</arm_group_label>
    <arm_group_label>Fructose and Glucose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults (18+ years or older) with a diagnosis of IBS-D or IBS-M based on Rome IV&#xD;
             criteria&#xD;
&#xD;
          -  Diarrhea must occur 2 or more days per week&#xD;
&#xD;
          -  Patients on current pharmacological therapy for their gastrointestinal complaints can&#xD;
             enroll in the study as long as they have been on a stable dose for at least 30 days.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Significant comorbidities that are associated with GI symptoms (e.g. diabetes,&#xD;
             scleroderma, SLE), history of GI surgery excluding appendectomy, or prior organic GI&#xD;
             illness&#xD;
&#xD;
          -  Antibiotics taken in the past 2 months&#xD;
&#xD;
          -  Current disordered eating patterns (diagnosed eating disorder; as per verbal ESP&#xD;
             questionnaire)&#xD;
&#xD;
          -  Current history of greater than moderate alcohol intake (more than 1 drink per day for&#xD;
             women, more than 2 drinks per day for men, binge drinking behavior of 5+ drinks in a&#xD;
             single session once per week)&#xD;
&#xD;
          -  Cannot have had a cholecystectomy in the past 6 months prior to enrollment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lin Chang, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Los Angeles</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UCLA</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>July 25, 2017</study_first_submitted>
  <study_first_submitted_qc>August 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2017</study_first_posted>
  <last_update_submitted>July 7, 2023</last_update_submitted>
  <last_update_submitted_qc>July 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, Los Angeles</investigator_affiliation>
    <investigator_full_name>Lin Chang, MD</investigator_full_name>
    <investigator_title>Director, Digestive Health and Nutrition Clinic</investigator_title>
  </responsible_party>
  <keyword>FODMAP</keyword>
  <keyword>IBS</keyword>
  <keyword>Diet</keyword>
  <keyword>Re-introduction</keyword>
  <keyword>Fructose</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Irritable Bowel Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Diarrhea</mesh_term>
  </condition_browse>
  <!-- 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/NCT03245645
org study id: 16-000934
nct id: NCT03245645
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to determine the amount and timing of when certain Fermentable
      Oligo-Di-Monosaccharides and Polyols (FODMAPs), specifically fructose, can be safely
      reintroduced into the diet of Irritable Bowel Syndrome (IBS) patients that have successfully
      completed a low-FODMAP elimination diet. The FODMAP diet is an effective treatment for IBS;
      however it is unclear how patients can successfully reintroduce and liberalize fructose into
      their diet. The low FODMAP diet is thought to reduce IBS symptoms by decreasing water content
      and gas production in the bowel and also possibly by altering gut bacteria. Although use of
      the FODMAP elimination diet can initially successfully treat IBS symptoms for up to 50-75% of
      patients, the reintroduction diet is difficult for patients to complete and maintain for long
      periods of time because current methods for reintroduction of FODMAPs are imprecise leading
      to frequent recurrent symptoms. As a result, patients often continue the low FODMAP
      elimination diet for additional months because they have difficulties knowing how to add back
      FODMAPs into their diet. There are no studies to date to help guide patients with FODMAP
      reintroduction.
Research supports clinical experience that ingestion of food often triggers the emergence or
      exacerbation of symptoms in the majority of patients with irritable bowel syndrome (IBS).
      While IBS remains primarily a symptom driven entity, our understanding of its pathophysiology
      is evolving. However, comparatively little research has focused on the specific role of
      certain foods and how they prompt the development of IBS symptoms.

      Food may be linked to changes in motility, visceral sensation, gut microbiome, intestinal
      permeability, immune activation and brain-gut axis. This study will focus on fructose, which
      is one of the main components of FODMAP (fermentable oligosaccharides, disacharides,
      mono-saccharides and polyols) foods. Fructose is a common part of the Western diet and can be
      consumed as a free monosaccharide, part of sucrose, or in polymers referred to as fructans.
      There are no human gut specific fructose transporters. Rather glucose transporters are used
      (GLUT 2,5) leading some to hypothesize that over ingestion of these agents may trigger some
      of the enteric complaints of patients with IBS. The literature on fructose malabsorption
      gives varying threshold amounts: from 15 to 50 grams in healthy controls, and from 5 to 50
      grams in IBS patients/known malabsorbers (Barrett, 2007; Rao, 2007; Frieling, 2011). Average
      daily fructose consumption in the American diet is approximately 34 grams, with a range of 15
      to 54 grams, which falls well within the threshold levels (Frieling, 2011). FODMAP foods are
      thought to induce gastrointestinal symptoms including gas, bloating, abdominal pain or
      discomfort, and loose stools by increasing small bowel water content and increasing gas
      production by fermentation of foods by gut bacteria. Studies including a recent controlled
      clinical trial demonstrated that a low FODMAP diet can be an effective nutritional therapy.

      There are risks to prolonged use of a low FODMAPs diet. A study from 2012 suggested that
      continued restriction of FODMAPS (longer than 4 weeks) can lead to reduction of luminal
      bifidobacteria in patients with IBS. Bifidobacteria mainly inhabit the large intestine where
      they produce short chain fatty acids (SCFA) as byproducts, including butyrate, shown to be
      important for colorectal cancer prevention and limit enteropathogenic colonization.
      Furthermore the diet is very restrictive and difficult for patients to maintain over time.

      However, important clinical questions include when FODMAPS can be safely reintroduced into
      the diet, how quickly this can be accomplished, and what is a daily threshold of intake that
      is acceptable for IBS patients who respond or do not respond to a low FODMAPs diet. There are
      no evidence based answers to these questions, and it is in this setting that we propose our
      current project.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Care Provider)
measure: Adequate relief of IBS symptoms in past 7 days
time frame: Baseline, 4 weeks (post-elimination diet)
description: As indicated by the study coordinator asking the participant "Have you had adequate relief of your IBS symptoms in the past 7 days?"
measure: Highest amount of grams of sugar in solutions that do not significantly increase IBS symptoms
time frame: Daily, during weeks 5-7 (reintroduction phase)
description: As measured by 100 MM Visual Analog Scale (VAS) with 0 representing no symptoms for overall gastrointestinal symptoms.
measure: Change in IBS-symptom severity scale
time frame: Baseline, 4 weeks (post-elimination diet), 7 weeks (post-reintroduction phase)
description: This is a validated symptom questionnaire pertaining to irritable bowel syndrome symptoms
measure: Change in Visceral Sensitivity Index (VSI)
time frame: Baseline, 4 weeks (post-elimination diet), 7 weeks (post-reintroduction phase)
description: This is a self-report measure of the gastrointestinal symptom-specific anxiety (GSA) of patients with irritable bowel syndrome (IBS)
measure: Change in Personal Health Questionnaire (PHQ-15)
time frame: Baseline, 4 weeks (post-elimination diet), 7 weeks (post-reintroduction phase)
description: This is a validated symptom questionnaire pertaining to somatic symptoms severity
measure: Change in abdominal pain severity
time frame: Baseline, 4 weeks (post-elimination diet), 7 weeks (post-reintroduction phase)
description: This is a self-report measure of the severity of abdominal pain during the week before report gathered by circling a number from 0-20 with 20 being the most intense pain imaginable.
measure: Change in overall severity of gastrointestinal symptoms
time frame: Baseline, 4 weeks (post-elimination diet), 7 weeks (post-reintroduction phase)
description: This is a self-report measure of the overall severity of gastrointestinal symptoms during the week before report gathered by circling a number from 0-20 with 20 being the most intense symptoms imaginable.
measure: Change in severity of the sensation of bloating, abdominal fullness or visible distension
time frame: Baseline, 4 weeks (post-elimination diet), 7 weeks (post-reintroduction phase)
description: This is a self-report measure of the severity of the sensation of bloating, abdominal fullness, or visible distension in the patient's belly that the patient has experienced during the week before report gathered by circling a number from 0-20 with 20 being the most intense sensation imaginable.
measure: Change in intestinal microbiota
time frame: Baseline, 4 weeks (post-elimination diet)
description: This is a measure of the intestinal microbiota 16S rRNA gene signatures in the patients' stool before and after the low FODMAP diet.
measure: Change in visceral sensitivity index score
time frame: Baseline, 4 weeks (post-elimination diet), 7 weeks (post-reintroduction phase)
description: This is a validated symptom questionnaire pertaining to gastrointestinal symptom related anxiety in patients with irritable bowel syndrome.
arm group label: 100% Fructose
arm group type: Experimental
description: The fructose group will help to determine whether an absolute amount of fructose will lead to IBS symptoms.
arm group label: 100% Glucose
arm group type: Placebo Comparator
description: The glucose group will serve as a control since glucose is not a FODMAP and as a result is not expected to lead to recurrent symptoms.
arm group label: Fructose and Glucose
arm group type: Active Comparator
description: The glucose/fructose mixture group is a cross comparison group that will determine whether the relative excess fructose concentration is an important cause of IBS symptoms.
intervention type: Other
intervention name: Dietary Intervention
description: Food may be linked to changes in motility, visceral sensation, gut microbiome, intestinal permeability, immune activation and brain-gut axis. This study will focus on fructose, which is one of the main components of FODMAP (Fermentable oligosaccharides, dissacharides, mono-saccharides and polyols) foods. Fructose is a common part of the Western diet and can be consumed as a free monosaccharide, part of sucrose, or in polymers referred to as fructans. FODMAP foods are thought to induce gastrointestinal symptoms including gas, bloating, abdominal pain or discomfort, and loose stools by increasing small bowel water content and increasing gas production by fermentation of foods by gut bacteria. Studies including a recent controlled clinical trial demonstrated that a low FODMAP diet can be an effective nutritional therapy.
arm group label: 100% Fructose
arm group label: 100% Glucose
arm group label: Fructose and Glucose
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lin Chang, MD
role: Principal Investigator
affiliation: University of California, Los Angeles
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of California, Los Angeles
investigator full name: Lin Chang, MD
investigator title: Director, Digestive Health and Nutrition Clinic
mesh term: Irritable Bowel Syndrome
mesh term: Syndrome
mesh term: Diarrhea