<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/NCT01675401</url>
  </required_header>
  <id_info>
    <org_study_id>MEC 12-3-040</org_study_id>
    <nct_id>NCT01675401</nct_id>
  </id_info>
  <brief_title>Body Weight and Vascular Function</brief_title>
  <official_title>Vascular Function Markers: Differences Between Lean and Abdominally Overweight / Obese Men and Effects of Weight Loss</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maastricht University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Top Institute Food and Nutrition</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Maastricht University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      An increased body mass impairs vascular function (VF), an important characteristic of&#xD;
      subjects suffering from type 2 diabetes and a risk marker for cardiovascular diseases.&#xD;
      However, a wide variety of in vivo VF markers exists each measuring different aspects of VF.&#xD;
      Each of these markers addresses a different aspect of the vasculature. Studies comparing&#xD;
      under standardized conditions the differences and relationships of the many different VF&#xD;
      measurements in lean and abdominally overweight / obese subjects are missing. Also, there is&#xD;
      a great need to know which of these markers are sensitive to dietary challenges.&#xD;
&#xD;
      Therefore, it is imperative to conduct an extensive study on dietary effects and&#xD;
      interrelationships of a broad spectrum of VF measurements and plasma biomarkers in lean and&#xD;
      overweight / obese subjects. Focus will be on FMD, a well accepted biomarker for&#xD;
      cardiovascular disease. The investigators propose to examine, in a two-way&#xD;
      parallel-randomized human intervention study, the effects of weight-loss in abdominally&#xD;
      overweight / obese men on VF markers and plasma biomarkers related to low-grade inflammation&#xD;
      and vascular activity during the fasting and both the postprandial and hyperinsulinemic&#xD;
      state. Furthermore, differences - and relations between - VF measurements and plasma&#xD;
      biomarkers will be compared cross-sectionally between lean and abdominally overweight / obese&#xD;
      male subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">May 2014</completion_date>
  <primary_completion_date type="Actual">May 2014</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Vascular activity: differences between lean and abdominally overweight / obese men and effects of weight loss</measure>
    <time_frame>Difference after weight-loss due to restriction of energy intake for 8 weeks and change from baseline at 2 hours after meal consumption</time_frame>
    <description>Flow-mediated dilation (FMD) of the brachial artery.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Vascular function markers related to the macrovasculature: differences between lean and abdominally overweight / obese men and effects of weight loss</measure>
    <time_frame>Difference after weight-loss due to restriction of energy intake for 8 weeks and change from baseline during the postprandial (at 2 hours after meal consumption) / hyperinsulinemic state (at 2 hours after initiation of the clamp)</time_frame>
    <description>Carotid-wall intima-media thickness (IMT), carotid compliance and distensibility, pulse wave velocity and analysis (PWV and PWA) and peripheral artery tonometry (PAT).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vascular function markers related to the microvasculature: differences between lean and abdominally overweight / obese men and effects of weight loss</measure>
    <time_frame>Difference after weight-loss due to restriction of energy intake for 8 weeks and change from baseline during the postprandial (at 1 and 3 hours after meal consumption) / hyperinsulinemic state (at 2 hours after initiation of the clamp)</time_frame>
    <description>Capillary video microscopy of the finger skin, skin microvascular vasomotion, glycocalyx thickness, retina photography, skin auto fluorescence and contrast enhanced ultrasound (CEUS) in skeletal muscle.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolic risk markers related to the metabolic syndrome: differences between lean and abdominally overweight / obese men and effects of weight loss</measure>
    <time_frame>Difference after weight-loss due to restriction of energy intake for 8 weeks and change from baseline during the postprandial (during 4 hours after meal consumption) / hyperinsulinemic state (during 3 hours after initiation of the clamp)</time_frame>
    <description>Biomarkers for low-grade inflammation and endothelial activation.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Body fat components and fat content of intra-abdominal organs: differences between lean and abdominally overweight / obese men and effects of weight loss</measure>
    <time_frame>Difference after weight-loss due to restriction of energy intake for 8 weeks</time_frame>
    <description>Dixon MRI measurements in order to quantify abdominal fat compartments (i.e. subcutaneous and visceral fat) and fat content of abdominal organs (i.e. liver).</description>
  </other_outcome>
  <other_outcome>
    <measure>Blood pressure: difference between lean and abdominally overweight / obese men and effects of weight loss</measure>
    <time_frame>Difference after weight-loss due to restriction of energy intake for 8 weeks</time_frame>
    <description>24-hr ambulatory blood pressure</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">75</enrollment>
  <condition>Metabolic Syndrome</condition>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>Weight-loss treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A very-low energy diet (Modifast Intensive) for 4-5 weeks providing 2.1 MJ/day in order to reduce body weight. After 4-5 weeks a mixed solid energy-restricted diet up to 4.2 MJ/day with a recommended composition for the following 1-2 weeks. Then, a diet matching their energy requirements to maintain newly achieved body weights (weight-stable conditions) for at least 2 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No-weight loss treatment</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Maintenance of habitual diet and physical activity for 8 weeks to maintain body weights.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Weight-loss treatment</intervention_name>
    <description>A very-low energy diet (Modifast Intensive) for 4-5 weeks providing 2.1 MJ/day in order to reduce body weight. After 4-5 weeks a mixed solid energy-restricted diet up to 4.2 MJ/day with a recommended composition for the following 1-2 weeks. Then, a diet matching their energy requirements to maintain newly achieved body weights (weight-stable conditions) for at least 2 weeks.</description>
    <arm_group_label>Weight-loss treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>No-weight loss treatment</intervention_name>
    <description>Maintenance of habitual diet and physical activity for 8 weeks to maintain body weights.</description>
    <arm_group_label>No-weight loss treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged between 18 and 65 years&#xD;
&#xD;
          -  Waist circumference below 94 cm (lean subjects) or between 102 - 110 cm (abdominally&#xD;
             overweight / obese subjects)&#xD;
&#xD;
          -  Caucasian&#xD;
&#xD;
          -  Plasma glucose &lt; 7.0 mmol/L&#xD;
&#xD;
          -  Serum total cholesterol &lt; 8.0 mmol/L&#xD;
&#xD;
          -  Serum triacylglycerol &lt; 4.5 mmol/L&#xD;
&#xD;
          -  Plasma HbA1c &lt; 6.5%&#xD;
&#xD;
          -  No current smoker&#xD;
&#xD;
          -  No diabetic patients&#xD;
&#xD;
          -  No familial hypercholesterolemia&#xD;
&#xD;
          -  No abuse of drugs&#xD;
&#xD;
          -  Less than 14 alcoholic consumptions per week&#xD;
&#xD;
          -  Stable body weight (weight gain or loss &lt; 3 kg in the past three months)&#xD;
&#xD;
          -  No use of medication known to affect blood pressure, serum lipid or glucose metabolism&#xD;
&#xD;
          -  No severe medical conditions that might interfere with the study, such as epilepsy,&#xD;
             asthma, chronic obstructive pulmonary disease, inflammatory bowel diseases, auto&#xD;
             inflammatory diseases and rheumatoid arthritis&#xD;
&#xD;
          -  No active cardiovascular disease like congestive heart failure or cardiovascular&#xD;
             event, such as an acute myocardial infarction or cerebrovascular accident&#xD;
&#xD;
          -  No contra-indications for MRI imaging&#xD;
&#xD;
          -  Willingness to give up being a blood donor (or having donated blood) from 8 weeks&#xD;
             before the start of the study, during the study and for 4 weeks after completion of&#xD;
             the study&#xD;
&#xD;
          -  No difficult venipuncture as evidenced during the screening visit&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women&#xD;
&#xD;
          -  Non-caucasian&#xD;
&#xD;
          -  Plasma glucose ≥ 7.0 mmol/L&#xD;
&#xD;
          -  Serum total cholesterol ≥ 8.0 mmol/L&#xD;
&#xD;
          -  Serum triacylglycerol ≥ 4.5 mmol/L&#xD;
&#xD;
          -  Plasma HbA1c ≥ 6.5%&#xD;
&#xD;
          -  Current smoker, or smoking cessation &lt; 12 months&#xD;
&#xD;
          -  Diabetic patients&#xD;
&#xD;
          -  Familial hypercholesterolemia&#xD;
&#xD;
          -  Abuse of drugs&#xD;
&#xD;
          -  More than 14 alcoholic consumptions per week&#xD;
&#xD;
          -  Unstable body weight (weight gain or loss &gt; 3 kg in the past three months)&#xD;
&#xD;
          -  Use of use of medication known to affect blood pressure, serum lipid or glucose&#xD;
             metabolism&#xD;
&#xD;
          -  Severe medical conditions that might interfere with the study, such as epilepsy,&#xD;
             asthma, chronic obstructive pulmonary disease, inflammatory bowel diseases, auto&#xD;
             inflammatory diseases and rheumatoid arthritis&#xD;
&#xD;
          -  Active cardiovascular disease like congestive heart failure or cardiovascular event,&#xD;
             such as an acute myocardial infarction or cerebrovascular accident&#xD;
&#xD;
          -  Contra-indications for MRI imaging&#xD;
&#xD;
          -  Use of an investigational product within the previous 1-month&#xD;
&#xD;
          -  Not willing to give up being a blood donor (or having donated blood) from 8 weeks&#xD;
             before the start of the study, during the study or for 4 weeks after completion of the&#xD;
             study&#xD;
&#xD;
          -  Not or difficult to venipuncture as evidenced during the screening visit&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ronald P Mensink, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Maastricht University Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Casper G Schalkwijk, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Maastricht University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Maastricht University Medical Center</name>
      <address>
        <city>Maastricht</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>October 2016</verification_date>
  <study_first_submitted>August 21, 2012</study_first_submitted>
  <study_first_submitted_qc>August 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 30, 2012</study_first_posted>
  <last_update_submitted>October 31, 2016</last_update_submitted>
  <last_update_submitted_qc>October 31, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 1, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Body Weight</keyword>
  <keyword>Obesity</keyword>
  <keyword>Weight Loss</keyword>
  <keyword>Vascular Function Markers</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metabolic Syndrome</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/NCT01675401
org study id: MEC 12-3-040
nct id: NCT01675401
lead sponsor: 
collaborator: 
has dmc: No
An increased body mass impairs vascular function (VF), an important characteristic of
      subjects suffering from type 2 diabetes and a risk marker for cardiovascular diseases.
      However, a wide variety of in vivo VF markers exists each measuring different aspects of VF.
      Each of these markers addresses a different aspect of the vasculature. Studies comparing
      under standardized conditions the differences and relationships of the many different VF
      measurements in lean and abdominally overweight / obese subjects are missing. Also, there is
      a great need to know which of these markers are sensitive to dietary challenges.

      Therefore, it is imperative to conduct an extensive study on dietary effects and
      interrelationships of a broad spectrum of VF measurements and plasma biomarkers in lean and
      overweight / obese subjects. Focus will be on FMD, a well accepted biomarker for
      cardiovascular disease. The investigators propose to examine, in a two-way
      parallel-randomized human intervention study, the effects of weight-loss in abdominally
      overweight / obese men on VF markers and plasma biomarkers related to low-grade inflammation
      and vascular activity during the fasting and both the postprandial and hyperinsulinemic
      state. Furthermore, differences - and relations between - VF measurements and plasma
      biomarkers will be compared cross-sectionally between lean and abdominally overweight / obese
      male subjects.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Single (Outcomes Assessor)
measure: Vascular activity: differences between lean and abdominally overweight / obese men and effects of weight loss
time frame: Difference after weight-loss due to restriction of energy intake for 8 weeks and change from baseline at 2 hours after meal consumption
description: Flow-mediated dilation (FMD) of the brachial artery.
measure: Vascular function markers related to the macrovasculature: differences between lean and abdominally overweight / obese men and effects of weight loss
time frame: Difference after weight-loss due to restriction of energy intake for 8 weeks and change from baseline during the postprandial (at 2 hours after meal consumption) / hyperinsulinemic state (at 2 hours after initiation of the clamp)
description: Carotid-wall intima-media thickness (IMT), carotid compliance and distensibility, pulse wave velocity and analysis (PWV and PWA) and peripheral artery tonometry (PAT).
measure: Vascular function markers related to the microvasculature: differences between lean and abdominally overweight / obese men and effects of weight loss
time frame: Difference after weight-loss due to restriction of energy intake for 8 weeks and change from baseline during the postprandial (at 1 and 3 hours after meal consumption) / hyperinsulinemic state (at 2 hours after initiation of the clamp)
description: Capillary video microscopy of the finger skin, skin microvascular vasomotion, glycocalyx thickness, retina photography, skin auto fluorescence and contrast enhanced ultrasound (CEUS) in skeletal muscle.
measure: Metabolic risk markers related to the metabolic syndrome: differences between lean and abdominally overweight / obese men and effects of weight loss
time frame: Difference after weight-loss due to restriction of energy intake for 8 weeks and change from baseline during the postprandial (during 4 hours after meal consumption) / hyperinsulinemic state (during 3 hours after initiation of the clamp)
description: Biomarkers for low-grade inflammation and endothelial activation.
measure: Body fat components and fat content of intra-abdominal organs: differences between lean and abdominally overweight / obese men and effects of weight loss
time frame: Difference after weight-loss due to restriction of energy intake for 8 weeks
description: Dixon MRI measurements in order to quantify abdominal fat compartments (i.e. subcutaneous and visceral fat) and fat content of abdominal organs (i.e. liver).
measure: Blood pressure: difference between lean and abdominally overweight / obese men and effects of weight loss
time frame: Difference after weight-loss due to restriction of energy intake for 8 weeks
description: 24-hr ambulatory blood pressure
arm group label: Weight-loss treatment
arm group type: Experimental
description: A very-low energy diet (Modifast Intensive) for 4-5 weeks providing 2.1 MJ/day in order to reduce body weight. After 4-5 weeks a mixed solid energy-restricted diet up to 4.2 MJ/day with a recommended composition for the following 1-2 weeks. Then, a diet matching their energy requirements to maintain newly achieved body weights (weight-stable conditions) for at least 2 weeks.
arm group label: No-weight loss treatment
arm group type: Other
description: Maintenance of habitual diet and physical activity for 8 weeks to maintain body weights.
intervention type: Other
intervention name: Weight-loss treatment
description: A very-low energy diet (Modifast Intensive) for 4-5 weeks providing 2.1 MJ/day in order to reduce body weight. After 4-5 weeks a mixed solid energy-restricted diet up to 4.2 MJ/day with a recommended composition for the following 1-2 weeks. Then, a diet matching their energy requirements to maintain newly achieved body weights (weight-stable conditions) for at least 2 weeks.
arm group label: Weight-loss treatment
intervention type: Other
intervention name: No-weight loss treatment
description: Maintenance of habitual diet and physical activity for 8 weeks to maintain body weights.
arm group label: No-weight loss treatment
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ronald P Mensink, PhD
role: Principal Investigator
affiliation: Maastricht University Medical Center
last name: Casper G Schalkwijk, PhD
role: Principal Investigator
affiliation: Maastricht University Medical Center
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Metabolic Syndrome