<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/NCT01707771</url>
  </required_header>
  <id_info>
    <org_study_id>HDL-2008</org_study_id>
    <nct_id>NCT01707771</nct_id>
  </id_info>
  <brief_title>Bariatric Surgery and HDL-cholesterol</brief_title>
  <official_title>Effect of Gastric Bypass Versus Diet on Cardiovascular Risk Factors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Catholic University of the Sacred Heart</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Catholic University of the Sacred Heart</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Objective: to assess the effect of gastric bypass on HDL-cholesterol concentration and its&#xD;
      Apolipoprotein A4 content at 1 year following bariatric surgery in comparison with a&#xD;
      hypocaloric diet. Secondary aim was to measure total cholesterol and triglycerides levels as&#xD;
      well as insulin sensitivity after interventions.&#xD;
&#xD;
      Summary Background Data: Very few prospective uncontrolled studies have investigated the&#xD;
      effects of Roux-en-Y gastric bypass (RYGB) on cardiovascular risk factors. No controlled&#xD;
      studies had as primary goal the changes in HDL-cholesterol after gastric bypass.&#xD;
&#xD;
      Methods: Forty subjects with a BMI&gt;40 or ≥35 kg/m2 in the presence of diabetes were enrolled.&#xD;
&#xD;
      Twenty of them were operated of RYGB while 20 received lifestyle modification suggestions and&#xD;
      medical therapy for obesity complications (diabetes, hypertension and hyperlipidemia).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study design The study was an unblinded, prospective, non randomized clinical trial.&#xD;
      Participants were recruited from referrals for treatment of morbid obesity between September&#xD;
      2008 and July 2009. One year follow-up was completed in September 2011.&#xD;
&#xD;
      The aim of the study related to the changes in HDL-cholesterol at 1 year after the&#xD;
      intervention. Secondary aims were the changes in Apolipoprotein 4 (Apo4) and insulin&#xD;
      sensitivity after the interventions.&#xD;
&#xD;
      Twenty morbidly-obese subjects (11 women and 9 men), whose 14 with normal glucose tolerance&#xD;
      and 6 with type 2 diabetes mellitus (T2DM), have been studied before and 1, 2, 3, 6, 9 and 12&#xD;
      months after bariatric surgery.&#xD;
&#xD;
      Twenty morbidly-obese subjects (12 women and 8 men), 15 with normal glucose tolerance and 5&#xD;
      with T2DM, in the waiting list for bariatric surgery were enrolled in the protocol and&#xD;
      underwent medical therapy for obesity complications (diabetes, hypertension and&#xD;
      hyperlipidemia) and lifestyle modification suggestions.&#xD;
&#xD;
      Participants were eligible for inclusion if they had a BMI of 40 kg/m2 or &gt;35 kg/m2 in&#xD;
      presence of type 2 diabetes, were aged 30 to 60 years, and had not sustained weight loss in&#xD;
      the previous 1 year. Exclusion criteria were a history of major abdominal or bariatric&#xD;
      surgery, disabling cardiac or pulmonary diseases, cancer, long-term treatment with oral&#xD;
      corticosteroids, and mental illness.&#xD;
&#xD;
      Roux-&amp;-Y Gastric Bypass (RYGB) involves the use of a surgical stapler to create a small and&#xD;
      vertically oriented gastric pouch with a volume usually &lt; 30 ml. The upper pouch is&#xD;
      completely divided by the gastric remnant and is anastomosed to the jejunum, 75 cm distally&#xD;
      to the Treitz's ligament , through a narrow gastrojejunal anastomosis in a Roux-en-Y fashion.&#xD;
      Bowel continuity is restored by an entero-entero anastomosis, between the excluded biliary&#xD;
      limb and the alimentary limb, performed at 150 cm from the gastrojejunostomy.&#xD;
&#xD;
      Lifestyle modifications A hypocaloric diet (15 kcal/kgbw containing 55% carbohydrates, 30%&#xD;
      lipids and 15% proteins) was prescribed together with the indications to perform 30 minutes&#xD;
      brisk walk each day. Patients had open access to a diabetologist every 3 months. Medical&#xD;
      therapies, including pharmaceutical agents, were assigned on an individual basis.&#xD;
&#xD;
      Anthropometric measures Body weight was measured to the nearest 0.1 kg with a beam scale and&#xD;
      height to the nearest 0.5 cm using a stadiometer (Holatin, Crosswell, Wales, U.K.).&#xD;
&#xD;
      Blood pressure Blood pressure was measured 3 times with an appropriately sized cuff after the&#xD;
      participant had rested for 5 minutes, and the last 2 measurements were averaged.&#xD;
&#xD;
      Oral glucose tolerance test A standard 75-g oral glucose tolerance test (OGTT) was performed&#xD;
      after an overnight fasting with blood sampling at 0, 30, 60, 90, 120, and 180 min. Samples&#xD;
      were placed in chilled tubes, and plasma was separated within 20 min and stored at -80°C.&#xD;
&#xD;
      Analytical methods Blood was drawn in the morning after an overnight fast. The sera and&#xD;
      plasma were immediately separated by centrifugation at 4°C and stored at -80°C until assay.&#xD;
&#xD;
      Plasma glucose was measured by the glucose-oxidase method (Beckman, Fullerton, CA). Plasma&#xD;
      insulin was assayed by microparticle-enzyme immunoassay (Abbott, Pasadena, CA) with a&#xD;
      sensitivity of 1 μU/ml and an intra-assay CV of 6.6%.&#xD;
&#xD;
      Total cholesterol and triglycerides were measured enzymatically. HDL-cholesterol was measured&#xD;
      after precipitating apolipoprotein B-containing lipoproteins with dextran sulfate and&#xD;
      magnesium chloride.&#xD;
&#xD;
      HbA1c serum levels were measured by high-performance liquid-chromatography (normal range&#xD;
      3.5-6.5%) Apo A4 was assessed by ELISA (Cusabio Biotech, Wuhan, Hubei, China); the detection&#xD;
      range is from 15.62 μg/l to 1000 μg/l and the minimum detectable concentration is 4 μg/l.&#xD;
&#xD;
      Insulin Sensitivity Models&#xD;
&#xD;
      The OGTT and fasting plasma glucose and insulin were used to compute the insulin sensitivity.&#xD;
      Insulin resistance was assessed using the homeostasis model assessment (HOMA-IR) originally&#xD;
      described by Mathew et al. HOMA-IR was calculated using the following equation:&#xD;
&#xD;
      HOMA-IR(μU/ml∙mg/dl)=fasting insulin(μU/ml)∙(fasting glucose (mg/dl))/405 Peripheral insulin&#xD;
      sensitivity was assessed by the Oral Glucose Insulin Sensitivity (OGIS) model. OGIS is an&#xD;
      index of insulin sensitivity calculated in this case from the 3 hours OGTT and it is an&#xD;
      estimate of the glucose clearance during a hyperinsulinemic euglycemic glucose clamp&#xD;
      expressed in ml/min per square meter of body surface area.&#xD;
&#xD;
      Statistics All of the data are expressed as means ± SD unless otherwise specified. The&#xD;
      Wilcoxon paired-sample test was used for intragroup comparisons. Two-sided P &lt; 0.05 was&#xD;
      considered significant. Nonparametric Spearman correlations were used to assess linear&#xD;
      relationships between single variables.&#xD;
&#xD;
      We calculated that a total of 30 participants would give 80% power to detect a significant (P&#xD;
      &lt; 0.05) difference between the groups. To allow for possible dropouts and add power for&#xD;
      analysis of secondary outcomes, we decided to enroll 40 participants.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2008</start_date>
  <completion_date type="Actual">September 2012</completion_date>
  <primary_completion_date type="Actual">September 2011</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>changes in HDL-cholesterol Baseline to 1 year HDL-cholesterol changes: baseline to 1 year</measure>
    <time_frame>1 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>changes in Apolipoprotein 4 (Apo4) and insulin sensitivity</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Morbid Obesity</condition>
  <arm_group>
    <arm_group_label>Roux-en-Y gastric bypass</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Both sexes, age between 30 and 60 years, BMI =/&gt; 35 kg/m2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>diet and lifestyle modifications</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Both sexes, age between 30 and 60 years, BMI =/&gt; 35 kg/m2</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Roux-en-Y gastric bypass</intervention_name>
    <description>Active Comparator: Roux-en-Y gastric bypass</description>
    <arm_group_label>Roux-en-Y gastric bypass</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>diet and lifestyle modifications</intervention_name>
    <description>Active Comparator: diet and lifestyle modifications</description>
    <arm_group_label>diet and lifestyle modifications</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  BMI =/&gt; 35 kg/m2,&#xD;
&#xD;
          -  age 30-60 years,&#xD;
&#xD;
          -  both sexes&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  history of major abdominal or bariatric surgery,&#xD;
&#xD;
          -  disabling cardiac or pulmonary diseases,&#xD;
&#xD;
          -  cancer,&#xD;
&#xD;
          -  long-term treatment with oral corticosteroids, and&#xD;
&#xD;
          -  mental illness&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Geltrude Mingrone, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Catholic University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Catholic University</name>
      <address>
        <city>Rome</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>October 2012</verification_date>
  <study_first_submitted>October 10, 2012</study_first_submitted>
  <study_first_submitted_qc>October 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 16, 2012</study_first_posted>
  <last_update_submitted>October 15, 2012</last_update_submitted>
  <last_update_submitted_qc>October 15, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 16, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Catholic University of the Sacred Heart</investigator_affiliation>
    <investigator_full_name>Geltrude Mingrone</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obesity, Morbid</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/NCT01707771
org study id: HDL-2008
nct id: NCT01707771
lead sponsor: 
has dmc: No
Objective: to assess the effect of gastric bypass on HDL-cholesterol concentration and its
      Apolipoprotein A4 content at 1 year following bariatric surgery in comparison with a
      hypocaloric diet. Secondary aim was to measure total cholesterol and triglycerides levels as
      well as insulin sensitivity after interventions.

      Summary Background Data: Very few prospective uncontrolled studies have investigated the
      effects of Roux-en-Y gastric bypass (RYGB) on cardiovascular risk factors. No controlled
      studies had as primary goal the changes in HDL-cholesterol after gastric bypass.

      Methods: Forty subjects with a BMI>40 or ≥35 kg/m2 in the presence of diabetes were enrolled.

      Twenty of them were operated of RYGB while 20 received lifestyle modification suggestions and
      medical therapy for obesity complications (diabetes, hypertension and hyperlipidemia).
Study design The study was an unblinded, prospective, non randomized clinical trial.
      Participants were recruited from referrals for treatment of morbid obesity between September
      2008 and July 2009. One year follow-up was completed in September 2011.

      The aim of the study related to the changes in HDL-cholesterol at 1 year after the
      intervention. Secondary aims were the changes in Apolipoprotein 4 (Apo4) and insulin
      sensitivity after the interventions.

      Twenty morbidly-obese subjects (11 women and 9 men), whose 14 with normal glucose tolerance
      and 6 with type 2 diabetes mellitus (T2DM), have been studied before and 1, 2, 3, 6, 9 and 12
      months after bariatric surgery.

      Twenty morbidly-obese subjects (12 women and 8 men), 15 with normal glucose tolerance and 5
      with T2DM, in the waiting list for bariatric surgery were enrolled in the protocol and
      underwent medical therapy for obesity complications (diabetes, hypertension and
      hyperlipidemia) and lifestyle modification suggestions.

      Participants were eligible for inclusion if they had a BMI of 40 kg/m2 or >35 kg/m2 in
      presence of type 2 diabetes, were aged 30 to 60 years, and had not sustained weight loss in
      the previous 1 year. Exclusion criteria were a history of major abdominal or bariatric
      surgery, disabling cardiac or pulmonary diseases, cancer, long-term treatment with oral
      corticosteroids, and mental illness.

      Roux-&-Y Gastric Bypass (RYGB) involves the use of a surgical stapler to create a small and
      vertically oriented gastric pouch with a volume usually < 30 ml. The upper pouch is
      completely divided by the gastric remnant and is anastomosed to the jejunum, 75 cm distally
      to the Treitz's ligament , through a narrow gastrojejunal anastomosis in a Roux-en-Y fashion.
      Bowel continuity is restored by an entero-entero anastomosis, between the excluded biliary
      limb and the alimentary limb, performed at 150 cm from the gastrojejunostomy.

      Lifestyle modifications A hypocaloric diet (15 kcal/kgbw containing 55% carbohydrates, 30%
      lipids and 15% proteins) was prescribed together with the indications to perform 30 minutes
      brisk walk each day. Patients had open access to a diabetologist every 3 months. Medical
      therapies, including pharmaceutical agents, were assigned on an individual basis.

      Anthropometric measures Body weight was measured to the nearest 0.1 kg with a beam scale and
      height to the nearest 0.5 cm using a stadiometer (Holatin, Crosswell, Wales, U.K.).

      Blood pressure Blood pressure was measured 3 times with an appropriately sized cuff after the
      participant had rested for 5 minutes, and the last 2 measurements were averaged.

      Oral glucose tolerance test A standard 75-g oral glucose tolerance test (OGTT) was performed
      after an overnight fasting with blood sampling at 0, 30, 60, 90, 120, and 180 min. Samples
      were placed in chilled tubes, and plasma was separated within 20 min and stored at -80°C.

      Analytical methods Blood was drawn in the morning after an overnight fast. The sera and
      plasma were immediately separated by centrifugation at 4°C and stored at -80°C until assay.

      Plasma glucose was measured by the glucose-oxidase method (Beckman, Fullerton, CA). Plasma
      insulin was assayed by microparticle-enzyme immunoassay (Abbott, Pasadena, CA) with a
      sensitivity of 1 μU/ml and an intra-assay CV of 6.6%.

      Total cholesterol and triglycerides were measured enzymatically. HDL-cholesterol was measured
      after precipitating apolipoprotein B-containing lipoproteins with dextran sulfate and
      magnesium chloride.

      HbA1c serum levels were measured by high-performance liquid-chromatography (normal range
      3.5-6.5%) Apo A4 was assessed by ELISA (Cusabio Biotech, Wuhan, Hubei, China); the detection
      range is from 15.62 μg/l to 1000 μg/l and the minimum detectable concentration is 4 μg/l.

      Insulin Sensitivity Models

      The OGTT and fasting plasma glucose and insulin were used to compute the insulin sensitivity.
      Insulin resistance was assessed using the homeostasis model assessment (HOMA-IR) originally
      described by Mathew et al. HOMA-IR was calculated using the following equation:

      HOMA-IR(μU/ml∙mg/dl)=fasting insulin(μU/ml)∙(fasting glucose (mg/dl))/405 Peripheral insulin
      sensitivity was assessed by the Oral Glucose Insulin Sensitivity (OGIS) model. OGIS is an
      index of insulin sensitivity calculated in this case from the 3 hours OGTT and it is an
      estimate of the glucose clearance during a hyperinsulinemic euglycemic glucose clamp
      expressed in ml/min per square meter of body surface area.

      Statistics All of the data are expressed as means ± SD unless otherwise specified. The
      Wilcoxon paired-sample test was used for intragroup comparisons. Two-sided P < 0.05 was
      considered significant. Nonparametric Spearman correlations were used to assess linear
      relationships between single variables.

      We calculated that a total of 30 participants would give 80% power to detect a significant (P
      < 0.05) difference between the groups. To allow for possible dropouts and add power for
      analysis of secondary outcomes, we decided to enroll 40 participants.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: changes in HDL-cholesterol Baseline to 1 year HDL-cholesterol changes: baseline to 1 year
time frame: 1 year
measure: changes in Apolipoprotein 4 (Apo4) and insulin sensitivity
time frame: 1 year
arm group label: Roux-en-Y gastric bypass
arm group type: Active Comparator
description: Both sexes, age between 30 and 60 years, BMI =/> 35 kg/m2
arm group label: diet and lifestyle modifications
arm group type: Active Comparator
description: Both sexes, age between 30 and 60 years, BMI =/> 35 kg/m2
intervention type: Procedure
intervention name: Roux-en-Y gastric bypass
description: Active Comparator: Roux-en-Y gastric bypass
arm group label: Roux-en-Y gastric bypass
intervention type: Behavioral
intervention name: diet and lifestyle modifications
description: Active Comparator: diet and lifestyle modifications
arm group label: diet and lifestyle modifications
criteria: 
gender: All
minimum age: 30 Years
maximum age: 60 Years
healthy volunteers: No
last name: Geltrude Mingrone, MD
role: Principal Investigator
affiliation: Catholic University
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: Catholic University of the Sacred Heart
investigator full name: Geltrude Mingrone
investigator title: Professor
mesh term: Obesity, Morbid