<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/NCT01725412</url>
  </required_header>
  <id_info>
    <org_study_id>Bio REB #12-59</org_study_id>
    <nct_id>NCT01725412</nct_id>
  </id_info>
  <brief_title>Prevention of Renal Complications of Diabetes With Thiamine</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Saskatchewan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Saskatchewan</source>
  <brief_summary>
    <textblock>
      Thiamine is a key component in the creation of physiologic anti-inflammatory mediators. Serum&#xD;
      thiamine stores have been found to be deficient in diabetic patients. Thiamine deficiency may&#xD;
      be a key pathological mechanism of inflammation that results in diabetic kidney and retinal&#xD;
      injury. The investigators hypothesize that the repletion of a patient's thiamine by oral&#xD;
      supplementation may result in reduced inflammation, and therefore reduced kidney injury.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Thiamine (vitamin B1) is a water-soluble vitamin. It is absorbed from the gastrointestinal&#xD;
      tract and taken up into tissues by transport proteins and converted to thiamine pyrophosphate&#xD;
      (TPP) by thiamine pyrophosphokinase (TPPK). TPP is a co-factor of pyruvate dehydrogenase&#xD;
      (PDH), α-ketoglutarate dehydrogenase and transketolase (TKT)-enzymes involved in the&#xD;
      metabolism of glucose.&#xD;
&#xD;
      Various transport proteins are involved in the transport of thiamine monophosphate (TMP) and&#xD;
      TPP across membranes. These include thiamine transported isoform-1 (THTR1) and thiamine&#xD;
      transporter isoform-2 (THTR2), reduced folate carrier-1 (RFC-1), which transports TMP and TPP&#xD;
      across cell plasma membranes and the mitochondrial TPP transporter (mTHTR). Thiamine and&#xD;
      TMP/TPP transporters may have abnormal expression in diabetes. Increased THTR1 levels are&#xD;
      found in red blood cells (RBCs) and mononuclear leucocytes of patients with diabetes compared&#xD;
      to those of healthy subjects. RBC precursors and leucocytes appeared to up-regulate THTR1&#xD;
      expression in response to decreased thiamine availability. In the presence of hyperglycemia,&#xD;
      renal tubular epithelial cells, by contrast, have decreased expression. In both experimental&#xD;
      models of diabetes and in human diabetics increased clearance of thiamine has been&#xD;
      demonstrated. This precedes the development of microalbuminuria. Patients with&#xD;
      microalbuminuria and early decline in glomerular filtration rate had higher fractional&#xD;
      excretion of thiamine compared to patients with stable renal function.&#xD;
&#xD;
      Thiamine supplementation in STZ- diabetic mice prevented the development of microalbuminuria,&#xD;
      decreasing urinary albumin excretion (UAE) by approximately 80%. In addition thiamine&#xD;
      supplementation prevented diuresis and glycosuria. Human studies are limited but in one&#xD;
      placebo controlled study the thiamine group showed a significant decrease in microalbuminuria&#xD;
      in diabetic patients on thiamine.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>November 2012</start_date>
  <primary_completion_date type="Anticipated">June 2013</primary_completion_date>
  <phase>Phase 4</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Microabluminuria</measure>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serum Thiamine Level</measure>
  </secondary_outcome>
  <other_outcome>
    <measure>Urinary Thiamine Level</measure>
  </other_outcome>
  <other_outcome>
    <measure>Inflammatory Markers</measure>
    <description>E-selectin, Intercellular Adhesion Molecule 1, von Willebrand Factor, malondialdehyde, glutathione, homocysteine, isoprotein F21, advanced glycation endproducts, receptor for advanced glycation endproducts</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Diabetic Nephropathy</condition>
  <arm_group>
    <arm_group_label>Thiamine Supplementation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Thiamine 300mg PO once daily</intervention_name>
    <arm_group_label>Thiamine Supplementation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  with a diagnosis of Type II diabetes which has been present for at least 5 years,&#xD;
&#xD;
          -  persistent microalbuminuria (30-299 mg/24 h),&#xD;
&#xD;
          -  HbA1c ≤ 8%, and&#xD;
&#xD;
          -  BMI 19-40 kg/m2.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  significant comorbidities,&#xD;
&#xD;
          -  &quot;deficient renal function&quot; known allergy or intolerance to thiamine,&#xD;
&#xD;
          -  use of thiamine supplements,&#xD;
&#xD;
          -  participation in an interventional study within 30 days,&#xD;
&#xD;
          -  recipients of renal and/or pancreatic transplant and&#xD;
&#xD;
          -  women who were pregnant or breast feeding.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dr. Gudrun Caspar-Bell, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Saskatchewan</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Gudrun Caspar-Bell, MD</last_name>
    <phone>306 966-2044</phone>
    <email>Gudrun.casparbell@saskatoonhealthregion.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Benjamin M Sehmer, MB</last_name>
    <phone>306 261 3932</phone>
    <email>benjamin.sehmer@usask.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Royal University Hospital</name>
      <address>
        <city>Saskatoon</city>
        <state>Saskatchewan</state>
        <zip>S7K 0M7</zip>
        <country>Canada</country>
      </address>
    </facility>
    <contact>
      <last_name>Gudrun Caspar-Bell</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>November 2012</verification_date>
  <study_first_submitted>November 8, 2012</study_first_submitted>
  <study_first_submitted_qc>November 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 12, 2012</study_first_posted>
  <last_update_submitted>November 9, 2012</last_update_submitted>
  <last_update_submitted_qc>November 9, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 12, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Saskatchewan</investigator_affiliation>
    <investigator_full_name>Gudrun Caspar-Bell</investigator_full_name>
    <investigator_title>Endocrinologist</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetic Nephropathies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thiamine</mesh_term>
  </intervention_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/NCT01725412
org study id: Bio REB #12-59
nct id: NCT01725412
lead sponsor: 
Thiamine is a key component in the creation of physiologic anti-inflammatory mediators. Serum
      thiamine stores have been found to be deficient in diabetic patients. Thiamine deficiency may
      be a key pathological mechanism of inflammation that results in diabetic kidney and retinal
      injury. The investigators hypothesize that the repletion of a patient's thiamine by oral
      supplementation may result in reduced inflammation, and therefore reduced kidney injury.
Thiamine (vitamin B1) is a water-soluble vitamin. It is absorbed from the gastrointestinal
      tract and taken up into tissues by transport proteins and converted to thiamine pyrophosphate
      (TPP) by thiamine pyrophosphokinase (TPPK). TPP is a co-factor of pyruvate dehydrogenase
      (PDH), α-ketoglutarate dehydrogenase and transketolase (TKT)-enzymes involved in the
      metabolism of glucose.

      Various transport proteins are involved in the transport of thiamine monophosphate (TMP) and
      TPP across membranes. These include thiamine transported isoform-1 (THTR1) and thiamine
      transporter isoform-2 (THTR2), reduced folate carrier-1 (RFC-1), which transports TMP and TPP
      across cell plasma membranes and the mitochondrial TPP transporter (mTHTR). Thiamine and
      TMP/TPP transporters may have abnormal expression in diabetes. Increased THTR1 levels are
      found in red blood cells (RBCs) and mononuclear leucocytes of patients with diabetes compared
      to those of healthy subjects. RBC precursors and leucocytes appeared to up-regulate THTR1
      expression in response to decreased thiamine availability. In the presence of hyperglycemia,
      renal tubular epithelial cells, by contrast, have decreased expression. In both experimental
      models of diabetes and in human diabetics increased clearance of thiamine has been
      demonstrated. This precedes the development of microalbuminuria. Patients with
      microalbuminuria and early decline in glomerular filtration rate had higher fractional
      excretion of thiamine compared to patients with stable renal function.

      Thiamine supplementation in STZ- diabetic mice prevented the development of microalbuminuria,
      decreasing urinary albumin excretion (UAE) by approximately 80%. In addition thiamine
      supplementation prevented diuresis and glycosuria. Human studies are limited but in one
      placebo controlled study the thiamine group showed a significant decrease in microalbuminuria
      in diabetic patients on thiamine.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Microabluminuria
measure: Serum Thiamine Level
measure: Urinary Thiamine Level
measure: Inflammatory Markers
description: E-selectin, Intercellular Adhesion Molecule 1, von Willebrand Factor, malondialdehyde, glutathione, homocysteine, isoprotein F21, advanced glycation endproducts, receptor for advanced glycation endproducts
arm group label: Thiamine Supplementation
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Dietary Supplement
intervention name: Thiamine 300mg PO once daily
arm group label: Thiamine Supplementation
intervention type: Dietary Supplement
intervention name: placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 30 Years
maximum age: 50 Years
healthy volunteers: No
last name: Dr. Gudrun Caspar-Bell, MD
role: Principal Investigator
affiliation: University of Saskatchewan
last name: Gudrun Caspar-Bell, MD
phone: 306 966-2044
email: Gudrun.casparbell@saskatoonhealthregion.ca
last name: Benjamin M Sehmer, MB
phone: 306 261 3932
email: benjamin.sehmer@usask.ca
facility: 
contact: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: University of Saskatchewan
investigator full name: Gudrun Caspar-Bell
investigator title: Endocrinologist
mesh term: Diabetic Nephropathies
mesh term: Thiamine