<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/NCT02974699</url>
  </required_header>
  <id_info>
    <org_study_id>110116M1F</org_study_id>
    <nct_id>NCT02974699</nct_id>
  </id_info>
  <brief_title>Role of Gastrointestinal Microbes on Digestion of Resistant Starch and Tryptophan Availability to Humans</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wayne State University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Wayne State University</source>
  <brief_summary>
    <textblock>
      There is currently a critical gap in knowledge of how intestinal bacterial communities alter&#xD;
      metabolic substrates available to the host thereby influencing central and enteric nervous&#xD;
      system (CNS/ENS) neurotransmitter levels involved in regulating carbohydrate consumption in&#xD;
      humans. Understanding these relationships is essential for developing strategies to improve&#xD;
      blood glucose control and to reduce the risk of transitioning from prediabetes to type-2&#xD;
      diabetes (T2D). The investigators' long-term goal is to determine the biological&#xD;
      underpinnings of behaviors that impact food intake and blood glucose control that contribute&#xD;
      to the development of T2D. The objective of this proposal, which is an essential next step in&#xD;
      attaining the investigators' long-term goals, is to determine how bacterial populations in&#xD;
      the digestive system impact circulating tryptophan (TRP) and large neutral amino acid (LNAA)&#xD;
      levels that regulate production of monoamine 5-hydroxytryptamine (5-HT, serotonin) in the ENS&#xD;
      and in gastrointestinal system and the brain. The central hypothesis is that a reduced ratio&#xD;
      of TRP producing (TRPp) to TRP consuming (TRPc) bacteria (decreased TRPp:TRPc ratio) in the&#xD;
      gut will decrease TRP availability following a carbohydrate meal lowering the plasma TRP:LNAA&#xD;
      ratio and resulting in less TRP for ENS/CNS production of 5HT. Further, dietary interventions&#xD;
      that promote TRPp bacterial abundance within the gut will increase TRP availability to the&#xD;
      host. The investigators will test the central hypothesis and, thereby, accomplish the overall&#xD;
      objective for this project by pursuing the following specific aims: 1) Assess impact of&#xD;
      divergent microbiota on plasma TRP:LNAA ratio in response to acute carbohydrate consumption,&#xD;
      and 2) Assess the impact of dietary supplementation with resistant starch (RS) on gut&#xD;
      microbiota and circulating TRP:LNAA ratio. During Aim 1, stool samples will be collected from&#xD;
      healthy participants. Participants will be stratified based on gut TRPp:TRPc ratio and the&#xD;
      response to an acute meal will be assessed by determining plasma TRP:LNAA ratios. During Aim&#xD;
      2 the capacity for 4-weeks of pre-biotic RS (Potato Starch) supplementation to increase the&#xD;
      TRPp:TRPc bacterial ratio in the gut will be determined from stool samples. Additionally,&#xD;
      plasma TRP:LNAA ratio following acute carbohydrate consumption before and after&#xD;
      supplementation will be determined. The scientific contribution will be to determine the&#xD;
      impact of RS on TRPp and TRPc bacteria abundance in the gut, and how bacterial populations&#xD;
      impact circulating TRP:LNAA levels, that can impact ENS and CNS 5HT production in humans.&#xD;
      This contribution will be significant because it will have direct translational implications&#xD;
      for human diseases with altered 5HT signaling.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2017</start_date>
  <primary_completion_date type="Anticipated">December 2017</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Plasma Amino Acid Levels</measure>
    <time_frame>Baseline</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma Amino Acid Levels</measure>
    <time_frame>Following 4 weeks of supplementation</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Plasma Amino Acid Levels</measure>
    <time_frame>Baseline vs. 4-weeks</time_frame>
    <description>Difference in plasma amino acid levels between baseline and following 4-weeks of supplementation</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Type II Diabetes</condition>
  <arm_group>
    <arm_group_label>Potato Starch (Bob's Red Mill)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Daily dietary supplementation with Potato Starch (48g total/day) suspended in water. 24g will be consumed 2 times per day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Resource ThickenUp Pregelatinized Starch</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Daily dietary supplementation with Pregelatinized Starch (48g total/day) suspended in water. 24g will be consumed 2 times per day.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Potato Starch (Bob's Red Mill)</intervention_name>
    <description>Subjects will be assigned to Potato Starch (active) following assessment of their gut microbiome.</description>
    <arm_group_label>Potato Starch (Bob's Red Mill)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Pregelatinized Starch (Resource ThickenUp)</intervention_name>
    <description>Subjects will be assigned to Pregelatinized Starch (placebo) following assessment of their gut microbiome.</description>
    <arm_group_label>Resource ThickenUp Pregelatinized Starch</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female&#xD;
&#xD;
          2. Age 18 - 65 years old&#xD;
&#xD;
          3. Non-Obese (BMI ≤ 30 kg/m2 and &gt;17 kg/m2 )&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Urine toxicology positive,&#xD;
&#xD;
          2. Pregnant (female)&#xD;
&#xD;
          3. Alcohol intake 48 hours prior to studies,&#xD;
&#xD;
          4. Evidence of inherited disorders of lipid metabolism,&#xD;
&#xD;
          5. History of Cancer within the last 5 years,&#xD;
&#xD;
          6. Human immunodeficiency virus (HIV) antibody positive,&#xD;
&#xD;
          7. Patients with solid organ transplants,&#xD;
&#xD;
          8. Unstable angina or NY heart association class II failure or above,&#xD;
&#xD;
          9. Gastrointestinal disease specifically GI motility disorders,&#xD;
&#xD;
         10. Unstable neuropsychiatric disease including major depression/anxiety, eating disorder&#xD;
             such as bulimia or anorexia,&#xD;
&#xD;
         11. End stage renal or hepatic disease,&#xD;
&#xD;
         12. Autoimmune disorders (e.g. SLE),&#xD;
&#xD;
         13. Prior bariatric surgery,&#xD;
&#xD;
         14. A history or current alcohol/substance abuse or nicotine containing products or&#xD;
             illicit drugs of abuse during the preceding 6 months,&#xD;
&#xD;
         15. Treatment within one month with sedative hypnotic medications (benzodiazepines,&#xD;
             barbiturates), or over the counter sleeping aids&#xD;
&#xD;
         16. Women: any selective estrogen receptor modulator or aromatase inhibitor Men:&#xD;
&#xD;
             androgen ablation/deprivation hormonal therapies&#xD;
&#xD;
         17. Any medical condition, which in the opinion of the investigator would make the patient&#xD;
             unsuitable for recruitment, or could interfere with the patient participating in or&#xD;
             completing the protocol&#xD;
&#xD;
         18. Any previous adverse events or allergic reactions to acetaminophen&#xD;
&#xD;
         19. Unwilling or unable to consent for the study.&#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>
  <overall_contact>
    <last_name>Paul R Burghardt, PhD</last_name>
    <phone>3135770107</phone>
    <email>paul.burghardt@wayne.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Katlin Chappelle, BS</last_name>
    <phone>3135772716</phone>
    <email>fx3603@wayne.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Wayne State University</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Paul Burghardt</last_name>
      <phone>313-577-0107</phone>
      <email>paul.burghardt@wayne.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>November 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 28, 2016</study_first_posted>
  <last_update_submitted>May 1, 2017</last_update_submitted>
  <last_update_submitted_qc>May 1, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 4, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Wayne State University</investigator_affiliation>
    <investigator_full_name>Paul Burghardt</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus, Type 2</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/NCT02974699
org study id: 110116M1F
nct id: NCT02974699
lead sponsor: 
There is currently a critical gap in knowledge of how intestinal bacterial communities alter
      metabolic substrates available to the host thereby influencing central and enteric nervous
      system (CNS/ENS) neurotransmitter levels involved in regulating carbohydrate consumption in
      humans. Understanding these relationships is essential for developing strategies to improve
      blood glucose control and to reduce the risk of transitioning from prediabetes to type-2
      diabetes (T2D). The investigators' long-term goal is to determine the biological
      underpinnings of behaviors that impact food intake and blood glucose control that contribute
      to the development of T2D. The objective of this proposal, which is an essential next step in
      attaining the investigators' long-term goals, is to determine how bacterial populations in
      the digestive system impact circulating tryptophan (TRP) and large neutral amino acid (LNAA)
      levels that regulate production of monoamine 5-hydroxytryptamine (5-HT, serotonin) in the ENS
      and in gastrointestinal system and the brain. The central hypothesis is that a reduced ratio
      of TRP producing (TRPp) to TRP consuming (TRPc) bacteria (decreased TRPp:TRPc ratio) in the
      gut will decrease TRP availability following a carbohydrate meal lowering the plasma TRP:LNAA
      ratio and resulting in less TRP for ENS/CNS production of 5HT. Further, dietary interventions
      that promote TRPp bacterial abundance within the gut will increase TRP availability to the
      host. The investigators will test the central hypothesis and, thereby, accomplish the overall
      objective for this project by pursuing the following specific aims: 1) Assess impact of
      divergent microbiota on plasma TRP:LNAA ratio in response to acute carbohydrate consumption,
      and 2) Assess the impact of dietary supplementation with resistant starch (RS) on gut
      microbiota and circulating TRP:LNAA ratio. During Aim 1, stool samples will be collected from
      healthy participants. Participants will be stratified based on gut TRPp:TRPc ratio and the
      response to an acute meal will be assessed by determining plasma TRP:LNAA ratios. During Aim
      2 the capacity for 4-weeks of pre-biotic RS (Potato Starch) supplementation to increase the
      TRPp:TRPc bacterial ratio in the gut will be determined from stool samples. Additionally,
      plasma TRP:LNAA ratio following acute carbohydrate consumption before and after
      supplementation will be determined. The scientific contribution will be to determine the
      impact of RS on TRPp and TRPc bacteria abundance in the gut, and how bacterial populations
      impact circulating TRP:LNAA levels, that can impact ENS and CNS 5HT production in humans.
      This contribution will be significant because it will have direct translational implications
      for human diseases with altered 5HT signaling.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Single (Participant)
measure: Plasma Amino Acid Levels
time frame: Baseline
measure: Plasma Amino Acid Levels
time frame: Following 4 weeks of supplementation
measure: Change in Plasma Amino Acid Levels
time frame: Baseline vs. 4-weeks
description: Difference in plasma amino acid levels between baseline and following 4-weeks of supplementation
arm group label: Potato Starch (Bob's Red Mill)
arm group type: Experimental
description: Daily dietary supplementation with Potato Starch (48g total/day) suspended in water. 24g will be consumed 2 times per day.
arm group label: Resource ThickenUp Pregelatinized Starch
arm group type: Placebo Comparator
description: Daily dietary supplementation with Pregelatinized Starch (48g total/day) suspended in water. 24g will be consumed 2 times per day.
intervention type: Dietary Supplement
intervention name: Potato Starch (Bob's Red Mill)
description: Subjects will be assigned to Potato Starch (active) following assessment of their gut microbiome.
arm group label: Potato Starch (Bob's Red Mill)
intervention type: Dietary Supplement
intervention name: Pregelatinized Starch (Resource ThickenUp)
description: Subjects will be assigned to Pregelatinized Starch (placebo) following assessment of their gut microbiome.
arm group label: Resource ThickenUp Pregelatinized Starch
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Paul R Burghardt, PhD
phone: 3135770107
email: paul.burghardt@wayne.edu
last name: Katlin Chappelle, BS
phone: 3135772716
email: fx3603@wayne.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Wayne State University
investigator full name: Paul Burghardt
investigator title: Assistant Professor
mesh term: Diabetes Mellitus, Type 2