<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/NCT04499183</url>
  </required_header>
  <id_info>
    <org_study_id>NL74418.081.20</org_study_id>
    <nct_id>NCT04499183</nct_id>
  </id_info>
  <brief_title>Fiber Fermentation, and Short Chain Fatty Acid Kinetics and Utilization Inside the Gut and Systemic Circulation</brief_title>
  <official_title>A Feasibility Study on Fiber Fermentation, and Short Chain Fatty Acid Kinetics and Utilization Inside the Gut and Systemic Circulation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wageningen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Wageningen University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Nowadays there is a strong interest in optimising human health through manipulation of&#xD;
      non-digestible carbohydrates (NDC). NDC can be used as substrates by gut microbiota, which&#xD;
      results in NDC degradation, production of fermentation products, such as short-chain fatty&#xD;
      acids (SCFA), and a shift in microbiome composition and activity. It is hypothesized that&#xD;
      SCFAs mediate parts of the beneficial effects of NDC. In mice, the influx of SCFA into the&#xD;
      host correlated strongly with improvements of markers of the metabolic syndrome, in contrast&#xD;
      to the concentrations of SCFA in the proximal colon. Therefore, the influx of short chain&#xD;
      fatty acids (SCFA) into the body may be of high importance in improving metabolism. There is&#xD;
      a need for more studies in humans to trace the life course of SCFA and their regulatory role&#xD;
      in human metabolism. To study this inner world of bacterial products in humans, we will use a&#xD;
      nasal-intestine catheter that can be used for delivery of components and sampling chyme in&#xD;
      the proximal colon. Before the proposed methodology can be applied in a large intervention&#xD;
      study, a small scale feasibility study needs to be performed that addresses colonic placement&#xD;
      of the nasal-intestine cathether and colonic sampling of regular and NDC-enriched chyme&#xD;
      samples. We will investigate the acute fermentation of fructo- and galacto-oligosaccharides&#xD;
      in the proximal colon. Moreover, we will deliver 13C-labelled SCFA via a naso-intestinal&#xD;
      catheter to quantify the fluxes of SCFA production, interconversion and uptake by the host. A&#xD;
      small-scale, 7-day parallel feasibility trial, N=5 subjects will receive GOS/FOS supplements&#xD;
      (mix 1:1 ratio, 15 gram/day), and N=5 other subjects will receive placebo supplements&#xD;
      (isocaloric maltodextrin, 12 gram/day). At the last day of the supplementation period, the&#xD;
      catheter will be placed, and afterwards participants stay maximum 5 hours in the hospital, to&#xD;
      ensure progression of the nose-intestine catheter. After an overnight fast, subjects will&#xD;
      visit the hospital again for measurements. Subjects will consume a NDC bolus (200 mL tap&#xD;
      water, 5 gram fructo-oligosaccharides, 5 gram galacto-oligosaccharides, non-absorbable marker&#xD;
      (PEG-4000). Afterwards, they are not allowed to eat for 6.5 hours. Isotopically 13C-labelled&#xD;
      SCFAs will be delivered in the proximal colon. Blood and colonic luminal samples, breath&#xD;
      samples, faeces and urine will be collected.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">October 8, 2020</start_date>
  <completion_date type="Anticipated">February 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">February 1, 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>Other</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Concentrations of carbohydrates</measure>
    <time_frame>Between 0 and 400 minutes</time_frame>
    <description>mono-, di-, tri-, oligo- and polysaccharides in the intestinal lumen</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Relative microbiota composition and metabolites</measure>
    <time_frame>Between 0 and 400 minutes</time_frame>
    <description>Microbiota and metabolites inside the intestine</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Concentrations of plasma metabolites</measure>
    <time_frame>Between 0 and 400 minutes</time_frame>
    <description>organic acids, amino acids, glucose, cholesterol, fatty acids and bile acids in blood</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Catheter placement in the colon</measure>
    <time_frame>After 1 week</time_frame>
    <description>To show placement of a naso-intestinal catheter in the proximal colon.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Volume of colon sample (mL)</measure>
    <time_frame>Between 0 and 400 minutes</time_frame>
    <description>To check whether enough material for analysis is obtained if the catheter system takes samples in the proximal colon of participants.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Concentrations of SCFAs</measure>
    <time_frame>Between 0 and 400 minutes</time_frame>
    <description>(13C isotopic) enrichments of SCFAs inside intestinal lumen</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Concentrations of urine metabolites</measure>
    <time_frame>After 0 and 120 minutes</time_frame>
    <description>hippurate, di- en tri-methylamine, acetaldehydes, taurine, glycine, glucuronic acid conjugates, and bile acid profiles (conjugates)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Questionnaires about (dis)comfort of study procedures</measure>
    <time_frame>After 1 week</time_frame>
    <description>Questions about study procedures</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relative microbiota composition and metabolite concentrations</measure>
    <time_frame>After 1 week</time_frame>
    <description>Microbiota and metabolome in faeces</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Concentrations of non-digestible markers</measure>
    <time_frame>Between 0 and 400 minutes</time_frame>
    <description>TiO2 and PEG-4000 inside the intestine</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Dietary Fiber</condition>
  <arm_group>
    <arm_group_label>non-digestible carbohydrates</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>fructo- and galacto-oligosaccharides</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>maltodextrin</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>fructo- and galacto-oligosaccharides</intervention_name>
    <description>15 gram/day fructo- and galacto-oligosaccharides</description>
    <arm_group_label>non-digestible carbohydrates</arm_group_label>
    <arm_group_label>placebo</arm_group_label>
    <other_name>FOS and GOS</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Males&#xD;
&#xD;
          -  Age 18-60yrs&#xD;
&#xD;
          -  BMI between 18.5 and 30 kg/m2&#xD;
&#xD;
          -  Regular bowel movement (defaecation on average once a day)&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Having a history of medical or surgical events that, in the opinion of the&#xD;
             Investigator, may either put the subject at risk because of participation in the&#xD;
             study, or influence the results of the study (e.g. diabetes, cardiovascular disease,&#xD;
             gastrointestinal disease, renal failure, cancer, infectious disease, nose/throat).&#xD;
&#xD;
          -  Having a history of surgical events of the gastro-intestinal tract (e.g. bariatric&#xD;
             surgery/gastric bypass surgery)&#xD;
&#xD;
          -  Presence of swallowing disorder&#xD;
&#xD;
          -  Use of any prescribed or non-prescribed medication (other than paracetamol) including&#xD;
             antacids, analgesics, and herbal remedies during the three (3) weeks prior to study&#xD;
             start.&#xD;
&#xD;
          -  Being lactose intolerant&#xD;
&#xD;
          -  Follows a vegan diet&#xD;
&#xD;
          -  Use of antibiotics within 3 months of starting the study or planned during the study&#xD;
&#xD;
          -  Use of pro- or prebiotics (e.g. galacto-oligosaccharides, fructo-oligosaccharides)&#xD;
&#xD;
          -  Constipation/infrequent bowel movement (less than 3 times defaecation per week)&#xD;
&#xD;
          -  Abuse of drugs/alcohol (alcohol: &gt;4 consumptions/day or &gt;21 consumptions/week)&#xD;
&#xD;
          -  Smoker&#xD;
&#xD;
          -  Having diarrhoea within 1 month prior to the study start&#xD;
&#xD;
          -  Personnel of Wageningen University, Division of Human Nutrition, their partner and&#xD;
             their first and second degree relatives&#xD;
&#xD;
          -  Participation in another biomedical study or other research from the Division of Human&#xD;
             Nutrition&#xD;
&#xD;
          -  Not willing to be exposed to fluoroscopy&#xD;
&#xD;
          -  Having a hemoglobin of &lt;8.5 mmol/L&#xD;
&#xD;
          -  Having blood vessels that are too difficult for inserting a cannula&#xD;
&#xD;
          -  Not having a general practitioner&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>MARA VAN TRIJP</last_name>
    <phone>0317 484 067</phone>
    <email>mara.vantrijp@wur.nl</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Guido Hooiveld</last_name>
    <email>guido.hooiveld@wur.nl</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Wageningen University and Research</name>
      <address>
        <city>Wageningen</city>
        <zip>6708 WE</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mara van Trijp, MSc</last_name>
      <email>mara.vantrijp@wur.nl</email>
    </contact>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>February 26, 2020</study_first_submitted>
  <study_first_submitted_qc>July 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>October 12, 2020</last_update_submitted>
  <last_update_submitted_qc>October 12, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT04499183
org study id: NL74418.081.20
nct id: NCT04499183
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Nowadays there is a strong interest in optimising human health through manipulation of
      non-digestible carbohydrates (NDC). NDC can be used as substrates by gut microbiota, which
      results in NDC degradation, production of fermentation products, such as short-chain fatty
      acids (SCFA), and a shift in microbiome composition and activity. It is hypothesized that
      SCFAs mediate parts of the beneficial effects of NDC. In mice, the influx of SCFA into the
      host correlated strongly with improvements of markers of the metabolic syndrome, in contrast
      to the concentrations of SCFA in the proximal colon. Therefore, the influx of short chain
      fatty acids (SCFA) into the body may be of high importance in improving metabolism. There is
      a need for more studies in humans to trace the life course of SCFA and their regulatory role
      in human metabolism. To study this inner world of bacterial products in humans, we will use a
      nasal-intestine catheter that can be used for delivery of components and sampling chyme in
      the proximal colon. Before the proposed methodology can be applied in a large intervention
      study, a small scale feasibility study needs to be performed that addresses colonic placement
      of the nasal-intestine cathether and colonic sampling of regular and NDC-enriched chyme
      samples. We will investigate the acute fermentation of fructo- and galacto-oligosaccharides
      in the proximal colon. Moreover, we will deliver 13C-labelled SCFA via a naso-intestinal
      catheter to quantify the fluxes of SCFA production, interconversion and uptake by the host. A
      small-scale, 7-day parallel feasibility trial, N=5 subjects will receive GOS/FOS supplements
      (mix 1:1 ratio, 15 gram/day), and N=5 other subjects will receive placebo supplements
      (isocaloric maltodextrin, 12 gram/day). At the last day of the supplementation period, the
      catheter will be placed, and afterwards participants stay maximum 5 hours in the hospital, to
      ensure progression of the nose-intestine catheter. After an overnight fast, subjects will
      visit the hospital again for measurements. Subjects will consume a NDC bolus (200 mL tap
      water, 5 gram fructo-oligosaccharides, 5 gram galacto-oligosaccharides, non-absorbable marker
      (PEG-4000). Afterwards, they are not allowed to eat for 6.5 hours. Isotopically 13C-labelled
      SCFAs will be delivered in the proximal colon. Blood and colonic luminal samples, breath
      samples, faeces and urine will be collected.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Double (Participant, Investigator)
measure: Concentrations of carbohydrates
time frame: Between 0 and 400 minutes
description: mono-, di-, tri-, oligo- and polysaccharides in the intestinal lumen
measure: Relative microbiota composition and metabolites
time frame: Between 0 and 400 minutes
description: Microbiota and metabolites inside the intestine
measure: Concentrations of plasma metabolites
time frame: Between 0 and 400 minutes
description: organic acids, amino acids, glucose, cholesterol, fatty acids and bile acids in blood
measure: Catheter placement in the colon
time frame: After 1 week
description: To show placement of a naso-intestinal catheter in the proximal colon.
measure: Volume of colon sample (mL)
time frame: Between 0 and 400 minutes
description: To check whether enough material for analysis is obtained if the catheter system takes samples in the proximal colon of participants.
measure: Concentrations of SCFAs
time frame: Between 0 and 400 minutes
description: (13C isotopic) enrichments of SCFAs inside intestinal lumen
measure: Concentrations of urine metabolites
time frame: After 0 and 120 minutes
description: hippurate, di- en tri-methylamine, acetaldehydes, taurine, glycine, glucuronic acid conjugates, and bile acid profiles (conjugates)
measure: Questionnaires about (dis)comfort of study procedures
time frame: After 1 week
description: Questions about study procedures
measure: Relative microbiota composition and metabolite concentrations
time frame: After 1 week
description: Microbiota and metabolome in faeces
measure: Concentrations of non-digestible markers
time frame: Between 0 and 400 minutes
description: TiO2 and PEG-4000 inside the intestine
arm group label: non-digestible carbohydrates
arm group type: Experimental
description: fructo- and galacto-oligosaccharides
arm group label: placebo
arm group type: Placebo Comparator
description: maltodextrin
intervention type: Dietary Supplement
intervention name: fructo- and galacto-oligosaccharides
description: 15 gram/day fructo- and galacto-oligosaccharides
arm group label: non-digestible carbohydrates
arm group label: placebo
other name: FOS and GOS
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: MARA VAN TRIJP
phone: 0317 484 067
email: mara.vantrijp@wur.nl
last name: Guido Hooiveld
email: guido.hooiveld@wur.nl
facility: 
status: Recruiting
contact: 
country: Netherlands
responsible party type: Sponsor