<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/NCT03032640</url>
  </required_header>
  <id_info>
    <org_study_id>TRIMDFH 982524</org_study_id>
    <nct_id>NCT03032640</nct_id>
  </id_info>
  <brief_title>Interactions of Human Gut Microbiota With Intestinal Sweet Taste Receptors</brief_title>
  <acronym>ISTAR-micro</acronym>
  <official_title>Interactions of Human Gut Microbiota With Intestinal Sweet Taste Receptors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AdventHealth Translational Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AdventHealth Translational Research Institute</source>
  <oversight_info>
    <has_dmc>Yes</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 collect data to examine whether short-term consumption of&#xD;
      non-caloric artificial sweeteners (NCASs), such as saccharin, can lead to changes in blood&#xD;
      sugar levels and in the composition of the bacteria in the large intestine.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 26, 2017</start_date>
  <completion_date type="Actual">October 18, 2022</completion_date>
  <primary_completion_date type="Actual">March 21, 2018</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>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Blood analyzed by way of NOVA StatStrip Meter and Milliplex Map Kit.</measure>
    <time_frame>6 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Short chain fatty acid analyses</measure>
    <time_frame>6 weeks</time_frame>
    <description>Stool sample aliquoted and frozen by way of ribosomal sequencing, which will be used to determine what bacteria is in the fecal sample.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">102</enrollment>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>Group 1- Healthy Lean subjects</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group 1 will receive Sodium Saccharin 200mg capsule, 2x/day, Day 1-14</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2- Healthy Lean subjects</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group 2 will receive Placebo 500mg capsule, 2x/day, Day 1-14</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3- Healthy Lean subjects</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group 3 will receive Sodium Saccharin 200mg + lactisole 335mg capsule, 2x/day, Day 1-14</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4- Healthy Lean subjects</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group 4 will receive Lactisole 335mg capsule, 2x/day, Day 1-14</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Oral Glucose Tolerance Test (OGTT)</intervention_name>
    <description>Once we test the fasting plasma glucose (after an overnight fast), subject will receive a 75g glucose beverage they will have to drink within 5 minutes. Then after drinking the beverage, 8 blood samples will be collected through the IV catheter, over the next 3 hours.</description>
    <arm_group_label>Group 1- Healthy Lean subjects</arm_group_label>
    <arm_group_label>Group 2- Healthy Lean subjects</arm_group_label>
    <arm_group_label>Group 3- Healthy Lean subjects</arm_group_label>
    <arm_group_label>Group 4- Healthy Lean subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Assessment of dietary compliance</intervention_name>
    <description>Assessment of consumption of non-caloric artificial sweeteners</description>
    <arm_group_label>Group 1- Healthy Lean subjects</arm_group_label>
    <arm_group_label>Group 2- Healthy Lean subjects</arm_group_label>
    <arm_group_label>Group 3- Healthy Lean subjects</arm_group_label>
    <arm_group_label>Group 4- Healthy Lean subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Stool sampling</intervention_name>
    <description>Subjects will provide a stool sample.</description>
    <arm_group_label>Group 1- Healthy Lean subjects</arm_group_label>
    <arm_group_label>Group 2- Healthy Lean subjects</arm_group_label>
    <arm_group_label>Group 3- Healthy Lean subjects</arm_group_label>
    <arm_group_label>Group 4- Healthy Lean subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Sodium Saccharin</intervention_name>
    <description>Subjects in group 1 and group 3 will be provided with sodium saccharin.</description>
    <arm_group_label>Group 1- Healthy Lean subjects</arm_group_label>
    <arm_group_label>Group 3- Healthy Lean subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Subjects in group 2 will be provided with placebo.</description>
    <arm_group_label>Group 2- Healthy Lean subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Lactisole</intervention_name>
    <description>Subjects in group 3 and group 4 will be provided with lactisole.</description>
    <arm_group_label>Group 3- Healthy Lean subjects</arm_group_label>
    <arm_group_label>Group 4- Healthy Lean subjects</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Able to provide written informed consent&#xD;
&#xD;
          2. Age 18-45 years&#xD;
&#xD;
          3. Weight stable (± 3 kg) during the 6 months prior to enrollment&#xD;
&#xD;
          4. BMI ≤ 25 kg/m2&#xD;
&#xD;
          5. Consumption of less than a can of diet beverage or a spoonful of NCASs weekly (or each&#xD;
             equivalent from foods) during the past month&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known coronary artery disease, angina or congestive heart failure&#xD;
&#xD;
          2. Type 1 or Type 2 Diabetes (A1c ≥6.5%)&#xD;
&#xD;
          3. Bleeding disorders&#xD;
&#xD;
          4. Hemoglobin level &lt; 12.5 g/dL for women; hemoglobin level &lt; 13.0 g/dL for men&#xD;
&#xD;
          5. Acute or chronic infections&#xD;
&#xD;
          6. Hepatitis and/or cirrhosis&#xD;
&#xD;
          7. Severe asthma or chronic obstructive pulmonary disease&#xD;
&#xD;
          8. Renal insufficiency or nephritis (creatinine &gt; 1.6 mg/dl)&#xD;
&#xD;
          9. Prior bariatric surgery&#xD;
&#xD;
         10. Inflammatory bowel disease or malabsorption&#xD;
&#xD;
         11. Cancer within the last 3 years (except non-melanoma skin cancer or treated cervical&#xD;
             carcinoma in situ)&#xD;
&#xD;
         12. Psychiatric disorders or eating disorders&#xD;
&#xD;
         13. Cushing's disease or syndrome&#xD;
&#xD;
         14. Untreated or inadequately controlled hypo- or hyperthyroidism (abnormal TSH)&#xD;
&#xD;
         15. Active rheumatoid arthritis or other inflammatory rheumatic disorder&#xD;
&#xD;
         16. Pregnant or nursing women&#xD;
&#xD;
         17. Smoking (smoking within the past 3 months)&#xD;
&#xD;
         18. Less than 4 bowel movements per week&#xD;
&#xD;
         19. Known hypersensitivity to saccharin, lactisole or any of its excipients.&#xD;
&#xD;
             Excluded medications include but are not limited to:&#xD;
&#xD;
         20. Anti-diabetic agents&#xD;
&#xD;
         21. Oral, injected or chronic topical steroids (inhaled steroids for mild asthma are&#xD;
             acceptable)&#xD;
&#xD;
         22. Antibiotic use (within the past 3 months)&#xD;
&#xD;
         23. Other drugs known to affect immune or metabolic function&#xD;
&#xD;
         24. Orlistat, phentermine, topiramate or other weight loss or anorectic agents (tricyclic&#xD;
             antidepressants, atypical antipsychotics or other psychiatric drugs with effects on&#xD;
             body weight)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Richard Pratley, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Translational Research Institute for Metabolism and Diabetes</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Translational Research Institute for Metabolism and Diabetes</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.tri-md.org</url>
    <description>Website for Translational Research Institute for Metabolism and Diabetes</description>
  </link>
  <reference>
    <citation>Swithers SE. Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends Endocrinol Metab. 2013 Sep;24(9):431-41. doi: 10.1016/j.tem.2013.05.005. Epub 2013 Jul 10.</citation>
    <PMID>23850261</PMID>
  </reference>
  <reference>
    <citation>Tilg H, Kaser A. Gut microbiome, obesity, and metabolic dysfunction. J Clin Invest. 2011 Jun;121(6):2126-32. doi: 10.1172/JCI58109. Epub 2011 Jun 1.</citation>
    <PMID>21633181</PMID>
  </reference>
  <reference>
    <citation>Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, Israeli D, Zmora N, Gilad S, Weinberger A, Kuperman Y, Harmelin A, Kolodkin-Gal I, Shapiro H, Halpern Z, Segal E, Elinav E. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014 Oct 9;514(7521):181-6. doi: 10.1038/nature13793. Epub 2014 Sep 17.</citation>
    <PMID>25231862</PMID>
  </reference>
  <reference>
    <citation>Saccharin and its salts. IARC Monogr Eval Carcinog Risks Hum. 1999;73:517-624. No abstract available.</citation>
    <PMID>10804968</PMID>
  </reference>
  <reference>
    <citation>Pantarotto C, Salmona M, Garattini S. Plasma kinetics and urinary elimination of saccharin in man. Toxicol Lett. 1981 Dec;9(4):367-71. doi: 10.1016/0378-4274(81)90012-6.</citation>
    <PMID>7330898</PMID>
  </reference>
  <reference>
    <citation>Sweatman TW, Renwick AG. The tissue distribution and pharmacokinetics of saccharin in the rat. Toxicol Appl Pharmacol. 1980 Aug;55(1):18-31. doi: 10.1016/0041-008x(80)90215-x. No abstract available.</citation>
    <PMID>7191585</PMID>
  </reference>
  <reference>
    <citation>Renwick AG. The metabolism of intense sweeteners. Xenobiotica. 1986 Oct-Nov;16(10-11):1057-71. doi: 10.3109/00498258609038983.</citation>
    <PMID>3541395</PMID>
  </reference>
  <reference>
    <citation>Arnold DL, Krewski D, Munro IC. Saccharin: a toxicological and historical perspective. Toxicology. 1983 Jul-Aug;27(3-4):179-256. doi: 10.1016/0300-483x(83)90021-5.</citation>
    <PMID>6353664</PMID>
  </reference>
  <reference>
    <citation>Sweatman TW, Renwick AG, Burgess CD. The pharmacokinetics of saccharin in man. Xenobiotica. 1981 Aug;11(8):531-40. doi: 10.3109/00498258109045864.</citation>
    <PMID>7303723</PMID>
  </reference>
  <reference>
    <citation>Renwick AG. The disposition of saccharin in animals and man--a review. Food Chem Toxicol. 1985 Apr-May;23(4-5):429-35. doi: 10.1016/0278-6915(85)90136-x.</citation>
    <PMID>3891556</PMID>
  </reference>
  <reference>
    <citation>Evaluation of certain food additives and contaminants. Forty-first report of the Joint FAO/WHO Expert Committee on Food Additives. World Health Organ Tech Rep Ser. 1993;837:1-53. No abstract available.</citation>
    <PMID>8266711</PMID>
  </reference>
  <reference>
    <citation>Food and Agriculture Organization World Health Organization. Evaluation of certain food additives. Fifty-ninth report of the Joint FAO/WHO Expert Committee on Food Additives. World Health Organ Tech Rep Ser. 2002;913:i-viii, 1-153, back cover.</citation>
    <PMID>12677645</PMID>
  </reference>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>November 11, 2016</study_first_submitted>
  <study_first_submitted_qc>January 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>February 1, 2023</last_update_submitted>
  <last_update_submitted_qc>February 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Glucose</keyword>
  <keyword>Sweet taste receptors</keyword>
  <keyword>Artificial sweeteners</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03032640
org study id: TRIMDFH 982524
nct id: NCT03032640
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to collect data to examine whether short-term consumption of
      non-caloric artificial sweeteners (NCASs), such as saccharin, can lead to changes in blood
      sugar levels and in the composition of the bacteria in the large intestine.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Blood analyzed by way of NOVA StatStrip Meter and Milliplex Map Kit.
time frame: 6 weeks
measure: Short chain fatty acid analyses
time frame: 6 weeks
description: Stool sample aliquoted and frozen by way of ribosomal sequencing, which will be used to determine what bacteria is in the fecal sample.
arm group label: Group 1- Healthy Lean subjects
arm group type: Active Comparator
description: Group 1 will receive Sodium Saccharin 200mg capsule, 2x/day, Day 1-14
arm group label: Group 2- Healthy Lean subjects
arm group type: Active Comparator
description: Group 2 will receive Placebo 500mg capsule, 2x/day, Day 1-14
arm group label: Group 3- Healthy Lean subjects
arm group type: Active Comparator
description: Group 3 will receive Sodium Saccharin 200mg + lactisole 335mg capsule, 2x/day, Day 1-14
arm group label: Group 4- Healthy Lean subjects
arm group type: Active Comparator
description: Group 4 will receive Lactisole 335mg capsule, 2x/day, Day 1-14
intervention type: Other
intervention name: Oral Glucose Tolerance Test (OGTT)
description: Once we test the fasting plasma glucose (after an overnight fast), subject will receive a 75g glucose beverage they will have to drink within 5 minutes. Then after drinking the beverage, 8 blood samples will be collected through the IV catheter, over the next 3 hours.
arm group label: Group 1- Healthy Lean subjects
arm group label: Group 2- Healthy Lean subjects
arm group label: Group 3- Healthy Lean subjects
arm group label: Group 4- Healthy Lean subjects
intervention type: Other
intervention name: Assessment of dietary compliance
description: Assessment of consumption of non-caloric artificial sweeteners
arm group label: Group 1- Healthy Lean subjects
arm group label: Group 2- Healthy Lean subjects
arm group label: Group 3- Healthy Lean subjects
arm group label: Group 4- Healthy Lean subjects
intervention type: Other
intervention name: Stool sampling
description: Subjects will provide a stool sample.
arm group label: Group 1- Healthy Lean subjects
arm group label: Group 2- Healthy Lean subjects
arm group label: Group 3- Healthy Lean subjects
arm group label: Group 4- Healthy Lean subjects
intervention type: Other
intervention name: Sodium Saccharin
description: Subjects in group 1 and group 3 will be provided with sodium saccharin.
arm group label: Group 1- Healthy Lean subjects
arm group label: Group 3- Healthy Lean subjects
intervention type: Other
intervention name: Placebo
description: Subjects in group 2 will be provided with placebo.
arm group label: Group 2- Healthy Lean subjects
intervention type: Other
intervention name: Lactisole
description: Subjects in group 3 and group 4 will be provided with lactisole.
arm group label: Group 3- Healthy Lean subjects
arm group label: Group 4- Healthy Lean subjects
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Richard Pratley, MD
role: Principal Investigator
affiliation: Translational Research Institute for Metabolism and Diabetes
facility: 
country: United States
url: http://www.tri-md.org
description: Website for Translational Research Institute for Metabolism and Diabetes
citation: Swithers SE. Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends Endocrinol Metab. 2013 Sep;24(9):431-41. doi: 10.1016/j.tem.2013.05.005. Epub 2013 Jul 10.
PMID: 23850261
citation: Tilg H, Kaser A. Gut microbiome, obesity, and metabolic dysfunction. J Clin Invest. 2011 Jun;121(6):2126-32. doi: 10.1172/JCI58109. Epub 2011 Jun 1.
PMID: 21633181
citation: Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, Israeli D, Zmora N, Gilad S, Weinberger A, Kuperman Y, Harmelin A, Kolodkin-Gal I, Shapiro H, Halpern Z, Segal E, Elinav E. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014 Oct 9;514(7521):181-6. doi: 10.1038/nature13793. Epub 2014 Sep 17.
PMID: 25231862
citation: Saccharin and its salts. IARC Monogr Eval Carcinog Risks Hum. 1999;73:517-624. No abstract available.
PMID: 10804968
citation: Pantarotto C, Salmona M, Garattini S. Plasma kinetics and urinary elimination of saccharin in man. Toxicol Lett. 1981 Dec;9(4):367-71. doi: 10.1016/0378-4274(81)90012-6.
PMID: 7330898
citation: Sweatman TW, Renwick AG. The tissue distribution and pharmacokinetics of saccharin in the rat. Toxicol Appl Pharmacol. 1980 Aug;55(1):18-31. doi: 10.1016/0041-008x(80)90215-x. No abstract available.
PMID: 7191585
citation: Renwick AG. The metabolism of intense sweeteners. Xenobiotica. 1986 Oct-Nov;16(10-11):1057-71. doi: 10.3109/00498258609038983.
PMID: 3541395
citation: Arnold DL, Krewski D, Munro IC. Saccharin: a toxicological and historical perspective. Toxicology. 1983 Jul-Aug;27(3-4):179-256. doi: 10.1016/0300-483x(83)90021-5.
PMID: 6353664
citation: Sweatman TW, Renwick AG, Burgess CD. The pharmacokinetics of saccharin in man. Xenobiotica. 1981 Aug;11(8):531-40. doi: 10.3109/00498258109045864.
PMID: 7303723
citation: Renwick AG. The disposition of saccharin in animals and man--a review. Food Chem Toxicol. 1985 Apr-May;23(4-5):429-35. doi: 10.1016/0278-6915(85)90136-x.
PMID: 3891556
citation: Evaluation of certain food additives and contaminants. Forty-first report of the Joint FAO/WHO Expert Committee on Food Additives. World Health Organ Tech Rep Ser. 1993;837:1-53. No abstract available.
PMID: 8266711
citation: Food and Agriculture Organization World Health Organization. Evaluation of certain food additives. Fifty-ninth report of the Joint FAO/WHO Expert Committee on Food Additives. World Health Organ Tech Rep Ser. 2002;913:i-viii, 1-153, back cover.
PMID: 12677645
responsible party type: Sponsor
sharing ipd: No