<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/NCT01677611</url>
  </required_header>
  <id_info>
    <org_study_id>NIG 35</org_study_id>
    <nct_id>NCT01677611</nct_id>
  </id_info>
  <brief_title>Effects of Resveratrol in Patients With Type 2 Diabetes</brief_title>
  <acronym>RED</acronym>
  <official_title>Effects of Resveratrol in Patients With Type 2 Diabetes: The RED Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Khoo Teck Puat Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Medical Research Council (NMRC), Singapore</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Khoo Teck Puat Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Animal studies indicate that resveratrol, a phytoalexin enriched in the skin of red grapes&#xD;
      and a constituent of red wine, is associated with longevity likely through the increased&#xD;
      production of a protein, SIRT1.&#xD;
&#xD;
      The trial is a proof-of-concept study primarily designed to examine for the first time in&#xD;
      humans, the effect of 12 weeks of oral resveratrol on skeletal muscle SIRT1 expression in 10&#xD;
      patients with T2DM in a randomized, placebo-controlled, double-blind fashion. Secondary&#xD;
      outcomes include measures of AMPK, p-AMPK and GLUT4 expression levels, energy expenditure,&#xD;
      physical activity levels, distribution of abdominal adipose tissue and skeletal muscle fiber&#xD;
      type composition, body weight, HbA1c, plasma lipid subfraction, adiponectin levels and&#xD;
      insulin sensitivity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Eligible criteria include Chinese males, aged between 40 and 69 years old, with T2DM with a&#xD;
      HbA1c of 7.1 to 12% and who have been on a stable oral hypoglycemic regimen for the past 3&#xD;
      months. Subjects who were insulin-dependent, with renal or liver impairment or who were&#xD;
      terminally ill were excluded.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2008</start_date>
  <completion_date type="Actual">March 2012</completion_date>
  <primary_completion_date type="Actual">September 2010</primary_completion_date>
  <phase>Phase 1</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Skeletal muscle sirtuin 1 (SIRT1) expression</measure>
    <time_frame>3 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Skeletal muscle 5'-AMP-activated protein kinase (AMPK) expression</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Skeletal muscle phosphorylated-AMPK-Thr172 (p-AMPK) expression</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Skeletal muscle glucose transporter type 4 (GLUT 4) expression</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glycated hemoglobin (HbA1c)</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body weight</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin sensitivity</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lipid profile</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Energy expenditure</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical activity level</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Abdominal adipose tissue distribution</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Skeletal muscle fibre type composition</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal function</measure>
    <time_frame>3 months</time_frame>
    <description>Serum creatinine</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Liver function</measure>
    <time_frame>3 months</time_frame>
    <description>Transaminases</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Type 2 Diabetes</condition>
  <arm_group>
    <arm_group_label>Resveratrol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Trans-resveratrol extract from Polygonum Cuspidatum (Mega Resveratrol, Danbury, USA) was used in the trial.Following the run-in period, subjects who were tolerant of the placebo would proceed to the treatment period. Subjects were given a starting dose of 500 mg daily of either resveratrol.The dose was increased by 500 mg per day every 3 days to a maximum dose of 3 g per day in three divided doses if there was no hypoglycemia. Subjects were instructed to abstain from foods with high resveratrol content during the entire duration of the trial.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>All subjects underwent a 2-week run-in period during which placebo was administered. The placebo was manufactured so that it was not distinguishable by color, form, or taste from the active drug. Following the run-in period, subjects who were tolerant of the placebo would proceed to the treatment period. Subjects were given a starting dose of 500 mg daily of matching placebo and instructed to abstain from foods with high resveratrol content during the entire duration of the trial. The dose was increased by 500 mg per day every 3 days to a maximum dose of 3 g per day in three divided doses if there was no hypoglycemia.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trans-resveratrol extract from Polygonum Cuspidatum</intervention_name>
    <description>Starting dose of 500 mg daily of either resveratrol to be administered on Day 1 and increased by 500 mg per day every 3 days to a maximum dose of 3 g per day in three divided doses if there was no hypoglycemia.</description>
    <arm_group_label>Resveratrol</arm_group_label>
    <other_name>Mega Resveratrol, Danbury, USA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Ability to give informed consent&#xD;
&#xD;
          2. Chinese Male&#xD;
&#xD;
          3. Age 40 to 69 yrs old&#xD;
&#xD;
          4. For subjects with type 2 diabetes mellitus&#xD;
&#xD;
               -  Diagnosis of type 2 diabetes mellitus based on MOH criteria and,&#xD;
&#xD;
               -  HbA1c &gt;6.5 during screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Willing to abstain from ingesting large quantities of resveratrol-containing foods (eg. red&#xD;
        wine, nuts) Cancer diagnosis that is currently under treatment, is clinically detectable,&#xD;
        or that has been treated within the past 5 years Terminal disease or on palliative care&#xD;
        Current excessive alcohol intake (&gt;21 units per week for men; 14 units per week for women)&#xD;
        On maximal doses of 3 or &gt; oral hypoglycaemic agents On insulin therapy or known type 1&#xD;
        diabetes mellitus Past history of documented or suspected hypoglycemia within last 3 months&#xD;
        Past history of recurrent hypoglycemia Past history of serious hypoglycemia as defined by&#xD;
        documented hypoglycemia requiring hospital admission Past history of hyperglycemic&#xD;
        emergencies within last 6 months Past or current history of hemorrhagic strokes On&#xD;
        anti-platelet agents, non-steroidal anti-inflammatory drugs (NSAIDs), anti-coagulation&#xD;
        therapy or omega-3 fatty acids History of unexplained bleeding disorders History of any&#xD;
        grape allergy History of allergy to local anaesthetic History of surgery with surgery with&#xD;
        clips, staples or stents Presence of cardiac pacemaker or metallic foreign body in any part&#xD;
        of the body On alternative or traditional medications Treated with another investigational&#xD;
        drug within last 6 months Poorly controlled hypertension (SBP &gt;/= 160 or DBP &gt;/= 100)&#xD;
        within last one month ALT and/or AST &gt; 1.5 times above upper limit of normal within last 6&#xD;
        months GFR &lt; 50 ml/min/1.73m2 (MDRD equation) within last 6 months&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>69 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kian Peng Goh, FRCP</last_name>
    <role>Principal Investigator</role>
    <affiliation>Alexandra Health, Khoo Teck Puat Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Alexandra Health, Khoo Teck Puat Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>768828</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <reference>
    <citation>Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006 Nov 16;444(7117):337-42. doi: 10.1038/nature05354. Epub 2006 Nov 1.</citation>
    <PMID>17086191</PMID>
  </reference>
  <reference>
    <citation>Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006 Dec 15;127(6):1109-22. doi: 10.1016/j.cell.2006.11.013. Epub 2006 Nov 16.</citation>
    <PMID>17112576</PMID>
  </reference>
  <reference>
    <citation>Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006 Jun;5(6):493-506. doi: 10.1038/nrd2060. Epub 2006 May 26.</citation>
    <PMID>16732220</PMID>
  </reference>
  <reference>
    <citation>Fujii N, Jessen N, Goodyear LJ. AMP-activated protein kinase and the regulation of glucose transport. Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E867-77. doi: 10.1152/ajpendo.00207.2006. Epub 2006 Jul 5.</citation>
    <PMID>16822958</PMID>
  </reference>
  <verification_date>August 2012</verification_date>
  <study_first_submitted>August 30, 2012</study_first_submitted>
  <study_first_submitted_qc>August 31, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2012</study_first_posted>
  <last_update_submitted>August 31, 2012</last_update_submitted>
  <last_update_submitted_qc>August 31, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 3, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Khoo Teck Puat Hospital</investigator_affiliation>
    <investigator_full_name>Kian Peng Goh</investigator_full_name>
    <investigator_title>Consultant</investigator_title>
  </responsible_party>
  <keyword>Resveratrol</keyword>
  <keyword>SIRT1</keyword>
  <keyword>AMPK</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Resveratrol</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/NCT01677611
org study id: NIG 35
nct id: NCT01677611
lead sponsor: 
collaborator: 
has dmc: Yes
Animal studies indicate that resveratrol, a phytoalexin enriched in the skin of red grapes
      and a constituent of red wine, is associated with longevity likely through the increased
      production of a protein, SIRT1.

      The trial is a proof-of-concept study primarily designed to examine for the first time in
      humans, the effect of 12 weeks of oral resveratrol on skeletal muscle SIRT1 expression in 10
      patients with T2DM in a randomized, placebo-controlled, double-blind fashion. Secondary
      outcomes include measures of AMPK, p-AMPK and GLUT4 expression levels, energy expenditure,
      physical activity levels, distribution of abdominal adipose tissue and skeletal muscle fiber
      type composition, body weight, HbA1c, plasma lipid subfraction, adiponectin levels and
      insulin sensitivity.
Eligible criteria include Chinese males, aged between 40 and 69 years old, with T2DM with a
      HbA1c of 7.1 to 12% and who have been on a stable oral hypoglycemic regimen for the past 3
      months. Subjects who were insulin-dependent, with renal or liver impairment or who were
      terminally ill were excluded.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Skeletal muscle sirtuin 1 (SIRT1) expression
time frame: 3 months
measure: Skeletal muscle 5'-AMP-activated protein kinase (AMPK) expression
time frame: 3 months
measure: Skeletal muscle phosphorylated-AMPK-Thr172 (p-AMPK) expression
time frame: 3 months
measure: Skeletal muscle glucose transporter type 4 (GLUT 4) expression
time frame: 3 months
measure: Glycated hemoglobin (HbA1c)
time frame: 3 months
measure: Body weight
time frame: 3 months
measure: Insulin sensitivity
time frame: 3 months
measure: Lipid profile
time frame: 3 months
measure: Energy expenditure
time frame: 3 months
measure: Physical activity level
time frame: 3 months
measure: Abdominal adipose tissue distribution
time frame: 3 months
measure: Skeletal muscle fibre type composition
time frame: 3 months
measure: Renal function
time frame: 3 months
description: Serum creatinine
measure: Liver function
time frame: 3 months
description: Transaminases
arm group label: Resveratrol
arm group type: Experimental
description: Trans-resveratrol extract from Polygonum Cuspidatum (Mega Resveratrol, Danbury, USA) was used in the trial.Following the run-in period, subjects who were tolerant of the placebo would proceed to the treatment period. Subjects were given a starting dose of 500 mg daily of either resveratrol.The dose was increased by 500 mg per day every 3 days to a maximum dose of 3 g per day in three divided doses if there was no hypoglycemia. Subjects were instructed to abstain from foods with high resveratrol content during the entire duration of the trial.
arm group label: Placebo
arm group type: Placebo Comparator
description: All subjects underwent a 2-week run-in period during which placebo was administered. The placebo was manufactured so that it was not distinguishable by color, form, or taste from the active drug. Following the run-in period, subjects who were tolerant of the placebo would proceed to the treatment period. Subjects were given a starting dose of 500 mg daily of matching placebo and instructed to abstain from foods with high resveratrol content during the entire duration of the trial. The dose was increased by 500 mg per day every 3 days to a maximum dose of 3 g per day in three divided doses if there was no hypoglycemia.
intervention type: Drug
intervention name: Trans-resveratrol extract from Polygonum Cuspidatum
description: Starting dose of 500 mg daily of either resveratrol to be administered on Day 1 and increased by 500 mg per day every 3 days to a maximum dose of 3 g per day in three divided doses if there was no hypoglycemia.
arm group label: Resveratrol
other name: Mega Resveratrol, Danbury, USA
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: Male
minimum age: 40 Years
maximum age: 69 Years
healthy volunteers: No
last name: Kian Peng Goh, FRCP
role: Principal Investigator
affiliation: Alexandra Health, Khoo Teck Puat Hospital
facility: 
country: Singapore
citation: Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006 Nov 16;444(7117):337-42. doi: 10.1038/nature05354. Epub 2006 Nov 1.
PMID: 17086191
citation: Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006 Dec 15;127(6):1109-22. doi: 10.1016/j.cell.2006.11.013. Epub 2006 Nov 16.
PMID: 17112576
citation: Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006 Jun;5(6):493-506. doi: 10.1038/nrd2060. Epub 2006 May 26.
PMID: 16732220
citation: Fujii N, Jessen N, Goodyear LJ. AMP-activated protein kinase and the regulation of glucose transport. Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E867-77. doi: 10.1152/ajpendo.00207.2006. Epub 2006 Jul 5.
PMID: 16822958
responsible party type: Principal Investigator
investigator affiliation: Khoo Teck Puat Hospital
investigator full name: Kian Peng Goh
investigator title: Consultant
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Resveratrol