<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/NCT01692002</url>
  </required_header>
  <id_info>
    <org_study_id>CRO2020</org_study_id>
    <nct_id>NCT01692002</nct_id>
  </id_info>
  <brief_title>Oral Propionate to Treat and Prevent Diabetes</brief_title>
  <official_title>Development of Orally Administered Sodium Propionate to Treat and Prevent Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Imperial College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Imperial College London</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 aim of these studies is to firstly determine the pharmacokinetic profile of orally&#xD;
      administered enteric coated sodium propionate. Subsequently, the most efficacious dose at&#xD;
      improving glucose tolerance following an oral glucose challenge will be determined. The&#xD;
      investigators will then determine the mechanism of action of propionate, whether it acts by&#xD;
      altering beta cell function directly or by augmenting the incretin effect or both&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The NHS spends £1M per hour, 10% of its yearly budget, treating diabetes. In the UK cases of&#xD;
      diabetes are expected to top 4 million by 2025. There is an urgent need for new therapies.&#xD;
      The short chain fatty acid propionate is a natural substance produced by digestion of&#xD;
      fermentable carbohydrates. Preclinical and early human data demonstrate it improves&#xD;
      pancreatic function and glucose control. The investigators aim to conduct proof of principle&#xD;
      studies to determine if oral delivery of propionate improves glucose control in patients at&#xD;
      risk of developing diabetes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2013</start_date>
  <completion_date type="Actual">August 2019</completion_date>
  <primary_completion_date type="Actual">August 2019</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>Crossover Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Study 1: Peak plasma concentration of propionate</measure>
    <time_frame>at -10, 0, 15, 30, 60, 90, 120, 150, 180, 4h, 6h, 8h</time_frame>
    <description>Dose ranging and pharmacokinetic profile</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Study 2: insulinogenic index</measure>
    <time_frame>0-30mins</time_frame>
    <description>oral glucose tolerance dose finding</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Study 3: Incremental area under the insulin profile</measure>
    <time_frame>0-10mins</time_frame>
    <description>Intravenous glucose tolerance test</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Insulin</measure>
    <time_frame>-10, 0, 15, 30, 60, 90, 120, 150, 180, 4h, 6h, 8h</time_frame>
    <description>Plasma insulin</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">90</enrollment>
  <condition>Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Sodium chloride pill</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Study 1: pharmacokinetics Study2: Oral glucose tolerance test Study 3: intravenous glucose tolerance test</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sodium propionate pill</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Study 1: pharmacokinetics Study2: Oral glucose tolerance test Study 3: intravenous glucose tolerance test</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Sodium propionate</intervention_name>
    <description>Sodium propionate capsule or tablet</description>
    <arm_group_label>Sodium propionate pill</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Sodium Chloride</intervention_name>
    <description>Placebo capsule or tablet</description>
    <arm_group_label>Sodium chloride pill</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Oral glucose tolerance test</intervention_name>
    <arm_group_label>Sodium chloride pill</arm_group_label>
    <arm_group_label>Sodium propionate pill</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Intravenous glucose tolerance test.</intervention_name>
    <arm_group_label>Sodium chloride pill</arm_group_label>
    <arm_group_label>Sodium propionate pill</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Study 1: Healthy men and women aged between 18 and 70 years with BMI between 20-25 kg/m2&#xD;
        and with normal fasting blood glucose (below5.5mmol/l and HbA1C less than 5.7% will be&#xD;
        eligible to volunteer.&#xD;
&#xD;
        Study 2: As for Study 1. Study 3: Cohort 1: Volunteers aged between 30 to 70 with a BMI&#xD;
        between 25-35 kg/m2 who do not have impaired fasting glucose and have HbA1c below 5.7%.&#xD;
&#xD;
        Cohort 2: Volunteers aged between 30 to 70 years with a BMI between 25-35 kg/m2 who have&#xD;
        impaired fasting glucose (between 5.5-7mmol/l) and HbA1C between 5.7% and 6.5%,&#xD;
&#xD;
          -  Exclusion Criteria:• Type 1 or Type 2 Diabetes&#xD;
&#xD;
               -  Gained or lost ≥ 3kg weight in the past three months&#xD;
&#xD;
               -  Taken prescription medicines having an impact on metabolism, appetite regulation,&#xD;
                  glucose homeostasis and hormonal regulation&#xD;
&#xD;
               -  Taken any dietary supplements in the last 6 months&#xD;
&#xD;
               -  Any chronic illness&#xD;
&#xD;
               -  Cardiovascular disease&#xD;
&#xD;
               -  Excess alcohol intake&#xD;
&#xD;
               -  Current smokers&#xD;
&#xD;
               -  Any gastrointestinal disorder e.g. Crohn's disease, coeliac disease or irritable&#xD;
                  bowel syndrome&#xD;
&#xD;
               -  A history of drug or alcohol abuse in the last 2 years&#xD;
&#xD;
               -  Pregnancy (all women of child bearing age will undergo a pregnancy test).&#xD;
&#xD;
               -  Pancreatitis&#xD;
&#xD;
               -  Use of medications likely to interfere with glucose metabolism, appetite&#xD;
                  regulation, hormonal balance.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gavin A Bewick, PhD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Imperial College London</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hammersmith Hospital</name>
      <address>
        <city>London</city>
        <state>UK</state>
        <zip>W12 0NN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imperial College London</name>
      <address>
        <city>London</city>
        <zip>W12 0NN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St John McMichael Centre - Imperial College London</name>
      <address>
        <city>London</city>
        <zip>W12 0NN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>September 11, 2012</study_first_submitted>
  <study_first_submitted_qc>September 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2012</study_first_posted>
  <last_update_submitted>October 14, 2019</last_update_submitted>
  <last_update_submitted_qc>October 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diabetes Mellitus</keyword>
  <keyword>Propionate</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>November 15, 2022</submitted>
  </pending_results>
  <!-- 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/NCT01692002
org study id: CRO2020
nct id: NCT01692002
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The aim of these studies is to firstly determine the pharmacokinetic profile of orally
      administered enteric coated sodium propionate. Subsequently, the most efficacious dose at
      improving glucose tolerance following an oral glucose challenge will be determined. The
      investigators will then determine the mechanism of action of propionate, whether it acts by
      altering beta cell function directly or by augmenting the incretin effect or both
The NHS spends £1M per hour, 10% of its yearly budget, treating diabetes. In the UK cases of
      diabetes are expected to top 4 million by 2025. There is an urgent need for new therapies.
      The short chain fatty acid propionate is a natural substance produced by digestion of
      fermentable carbohydrates. Preclinical and early human data demonstrate it improves
      pancreatic function and glucose control. The investigators aim to conduct proof of principle
      studies to determine if oral delivery of propionate improves glucose control in patients at
      risk of developing diabetes.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Study 1: Peak plasma concentration of propionate
time frame: at -10, 0, 15, 30, 60, 90, 120, 150, 180, 4h, 6h, 8h
description: Dose ranging and pharmacokinetic profile
measure: Study 2: insulinogenic index
time frame: 0-30mins
description: oral glucose tolerance dose finding
measure: Study 3: Incremental area under the insulin profile
time frame: 0-10mins
description: Intravenous glucose tolerance test
measure: Insulin
time frame: -10, 0, 15, 30, 60, 90, 120, 150, 180, 4h, 6h, 8h
description: Plasma insulin
arm group label: Sodium chloride pill
arm group type: Placebo Comparator
description: Study 1: pharmacokinetics Study2: Oral glucose tolerance test Study 3: intravenous glucose tolerance test
arm group label: Sodium propionate pill
arm group type: Experimental
description: Study 1: pharmacokinetics Study2: Oral glucose tolerance test Study 3: intravenous glucose tolerance test
intervention type: Dietary Supplement
intervention name: Sodium propionate
description: Sodium propionate capsule or tablet
arm group label: Sodium propionate pill
intervention type: Dietary Supplement
intervention name: Sodium Chloride
description: Placebo capsule or tablet
arm group label: Sodium chloride pill
intervention type: Procedure
intervention name: Oral glucose tolerance test
arm group label: Sodium chloride pill
arm group label: Sodium propionate pill
intervention type: Procedure
intervention name: Intravenous glucose tolerance test.
arm group label: Sodium chloride pill
arm group label: Sodium propionate pill
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Gavin A Bewick, PhD.
role: Principal Investigator
affiliation: Imperial College London
facility: 
facility: 
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Diabetes Mellitus
sharing ipd: No
submitted: November 15, 2022