<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/NCT02244814</url>
  </required_header>
  <id_info>
    <org_study_id>14-1358</org_study_id>
    <nct_id>NCT02244814</nct_id>
  </id_info>
  <brief_title>Trial of Diet in Gestational Diabetes Mellitus: Metabolic Consequences to Mother and Offspring</brief_title>
  <acronym>CHOICE</acronym>
  <official_title>Randomized Trial of Diet in Gestational Diabetes Mellitus: Metabolic Consequences to Mother and Offspring</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Colorado, Denver</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The rapidly rising risk of gestational diabetes pregnant women demands that an effective diet&#xD;
      strategy be developed due to the high risk of fetal overgrowth, which places the newborn at&#xD;
      increased risk for childhood obesity and metabolic syndrome. The aims of this randomized&#xD;
      clinical trial are to compare the effects of an 8-wk isocaloric higher complex&#xD;
      carbohydrate/lower fat diet vs. a conventional lower carbohydrate (higher fat) diet on&#xD;
      glycemic and lipid profiles, maternal insulin resistance, placenta nutrient transporters, the&#xD;
      maternal microbiome, neonatal intrahepatic fat, and neonatal total adiposity (primary&#xD;
      outcome). The investigators will then follow the infants for 1-yr and measure maternal breast&#xD;
      milk and infant microbiome composition to observe if they impact net fat mass gain&#xD;
      differently in infants exposed to one diet vs. the other. Identifying a diet for gestational&#xD;
      diabetes mellitus women that can effectively alter maternal/fetal metabolism is critical to&#xD;
      reducing short- and long-term metabolic risk in this growing cohort of mothers and infants&#xD;
      and has the potential to be applicable to overweight/obese pregnant women.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The rapidly rising incidence of gestational diabetes mellitus in overweight/obese pregnant&#xD;
      women demands that an effective diet strategy be developed due to the high risk of fetal&#xD;
      overgrowth, which places the newborn at increased risk for childhood obesity and metabolic&#xD;
      syndrome. However, the lack of adequate controlled randomized clinical trials for treatment&#xD;
      of gestational diabetes with diet has resulted in consensus panels abandoning any specific&#xD;
      diet recommendation. If effective, diet therapy has the potential to avoid the high costs of&#xD;
      medical treatment and intensified fetal monitoring for this growing population. Although a&#xD;
      low carbohydrate diet has historically been advocated to decrease glucose excursions after&#xD;
      meals, carbohydrate has typically been replaced by higher fat which has been shown in animal&#xD;
      and non-human primate data to promote insulin resistance, glucose intolerance, and liver fat&#xD;
      deposition in the offspring. In fact, recent human data suggest that high maternal&#xD;
      triglycerides and free fatty acids, variables sensitive to dietary manipulation, may be at&#xD;
      least as important as glucose in contributing to excess fetal growth and infant adiposity.&#xD;
      Preliminary data based on an R21, show that compared to a conventional lower-carbohydrate&#xD;
      (higher in fat) diet, providing a higher complex carbohydrate (lower fat) diet effectively&#xD;
      blunts postprandial glucose and improves fasting glucose and insulin after 6-7 weeks, with&#xD;
      less adiposity in the newborn. The investigators global hypothesis is that compared to 8&#xD;
      weeks of a low-carbohydrate/higher fat diet, a higher complex carbohydrate/lower fat diet&#xD;
      will blunt maternal post-prandial free fatty acids and improve insulin resistance. Improved&#xD;
      insulin sensitivity will reduce fetal over-nutrition by decreasing substrate availability and&#xD;
      down-regulating placental nutrient transporters, thereby reducing neonatal adiposity (primary&#xD;
      outcome).This proposal builds on the investigators R21 study, which is the first randomized&#xD;
      clinical trial to provide all meals from the time of gestational diabetes diagnosis&#xD;
      throughout the remainder of pregnancy. The aims of this randomized trial are to compare the&#xD;
      effects of an 8-wk isocaloric higher complex carbohydrate/lower fat diet (60%&#xD;
      carbohydrate/25% fat) vs. a conventional low-carbohydrate (higher fat)(40% carbohydrate/45%&#xD;
      fat) diet on maternal insulin resistance, placental nutrient transporters, and neonatal fat&#xD;
      development. Innovative approaches by the investigators skilled multidisciplinary team&#xD;
      include: maternal insulin resistance systemically (oral glucose tolerance Index) and locally&#xD;
      (adipose tissue lipolysis); intestinal microbiome (transferred to the newborn); and neonatal&#xD;
      intrahepatic fat (magnetic resonance spectroscopy). Persistence of neonatal adiposity is&#xD;
      relevant to understanding obesity risk in these infants. As the investigators pilot data&#xD;
      suggest infant microbiome and breast milk composition impact fat accrual after birth, the&#xD;
      investigators will follow the infants through 1-yr of life accounting for these variables.&#xD;
      Identifying a diet for gestational diabetes that can effectively alter maternal/fetal&#xD;
      metabolism in late pregnancy when fetal growth accelerates is critical to reducing short- and&#xD;
      long-term metabolic risk in this growing cohort of mothers and infants. The study results&#xD;
      could lead to a paradigm shift for diet therapy in gestational diabetes, with potential&#xD;
      widespread application to pregnancies affected by obesity alone.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2015</start_date>
  <completion_date type="Actual">November 2020</completion_date>
  <primary_completion_date type="Actual">November 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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Neonatal adiposity</measure>
    <time_frame>5-7 days after birth</time_frame>
    <description>Air-displacement plethysmography</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maternal Insulin Resistance</measure>
    <time_frame>36 wks gestation</time_frame>
    <description>Between-diet difference in post-prandial free fatty acid area-under-the-curve as a surrogate for insulin resistance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Placental fatty acid transporter protein-2 expression</measure>
    <time_frame>Delivery</time_frame>
    <description>Between diet-difference in protein expression of placental fatty acid transporter protein-2.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Oral glucose tolerance test</measure>
    <time_frame>Baseline, 36 wks</time_frame>
    <description>75g oral glucose tolerance test; calculated Index to assess diet-induced differences in maternal insulin resistance.</description>
  </other_outcome>
  <other_outcome>
    <measure>Adipose Tissue Lipolysis</measure>
    <time_frame>Baseline, 36 wks</time_frame>
    <description>Diet-induced difference in adipose tissue lipolysis.</description>
  </other_outcome>
  <other_outcome>
    <measure>Infant Adiposity</measure>
    <time_frame>Birth-12 mos</time_frame>
    <description>Infant adiposity (air displacement plethysmography, anthropometry) from delivery - 1 year (dual x-ray absorptiometry)</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">105</enrollment>
  <condition>Gestational Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Choosing Healthy Options in Carbohydrate Energy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>60% carbohydrate/25% fat/15% protein diet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low Carbohydrate/Conventional</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>40% carbohydrate/45% fat/15% protein</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Low Carbohydrate/Conventional</intervention_name>
    <description>Lower-carbohydrate/conventional diet (usual care)</description>
    <arm_group_label>Choosing Healthy Options in Carbohydrate Energy</arm_group_label>
    <arm_group_label>Low Carbohydrate/Conventional</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Choosing Healthy Options in Carbohydrate Energy</intervention_name>
    <description>Choosing Healthy Options in Carbohydrate Energy</description>
    <arm_group_label>Choosing Healthy Options in Carbohydrate Energy</arm_group_label>
    <arm_group_label>Low Carbohydrate/Conventional</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pregnant women will be between the ages of 20-36 yrs&#xD;
&#xD;
          -  BMI of 26-39 kg/m2 at the time of diagnosis&#xD;
&#xD;
          -  singleton pregnancy&#xD;
&#xD;
          -  no oral hypoglycemic therapy before entering the study&#xD;
&#xD;
          -  diagnosed with Gestational diabetes according to the criteria established by the&#xD;
             American College of Obstetricians and Gynecologists, specifically, they will have 2&#xD;
             abnormal values on a 100-g 3 hr glucose tolerance test 205, 206: Fasting&gt;95 mg/dL but&#xD;
             &lt;105 mg/dL; 1hr&gt; 180 mg/dL; 2 hr&gt;155 mg/dL; 3 hr&gt;140 mg/dL.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  extreme hypertriglyceridemia&#xD;
&#xD;
          -  overt diabetes&#xD;
&#xD;
          -  suspected preexisting diabetes (A1C≥6.5%, Fasting glucose&gt;125 mg/dL, or random glucose&#xD;
             &gt;200/mg/dL)&#xD;
&#xD;
          -  women highly likely to fail diet by any of the following criteria will be excluded:1)&#xD;
             Fasting glucose &gt;105 mg/dL, due to the higher likelihood of failing diet and requiring&#xD;
             medical treatment 139; 2) Fasting triglyceride &gt; 400 mg/dL.&#xD;
&#xD;
          -  non-English speaking&#xD;
&#xD;
          -  Smokers (leading cause of low birth weight)&#xD;
&#xD;
          -  Risk factors for placental insufficiency (hypertension, renal disease, thrombophilias,&#xD;
             rheumatologic disease, preeclampsia, steroid use, history of pancreatitis, infectious&#xD;
             disease, or intrauterine growth restriction)&#xD;
&#xD;
          -  History of pancreatitis&#xD;
&#xD;
          -  History of pre-term labor&#xD;
&#xD;
          -  Taking beta blockers/glucocorticoids&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>36 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Teri L Hernandez, PhD, RN</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Colorado/Anschutz Medical Campus</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Hernandez TL, Van Pelt RE, Anderson MA, Daniels LJ, West NA, Donahoo WT, Friedman JE, Barbour LA. A higher-complex carbohydrate diet in gestational diabetes mellitus achieves glucose targets and lowers postprandial lipids: a randomized crossover study. Diabetes Care. 2014;37(5):1254-62. doi: 10.2337/dc13-2411. Epub 2014 Mar 4.</citation>
    <PMID>24595632</PMID>
  </reference>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>September 15, 2014</study_first_submitted>
  <study_first_submitted_qc>September 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 19, 2014</study_first_posted>
  <last_update_submitted>December 17, 2020</last_update_submitted>
  <last_update_submitted_qc>December 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>glucose</keyword>
  <keyword>insulin resistance</keyword>
  <keyword>dietary carbohydrate</keyword>
  <keyword>dietary fat</keyword>
  <keyword>adiposity</keyword>
  <keyword>Air displacement plethysmography</keyword>
  <keyword>Dual X-ray Absorptiometry</keyword>
  <keyword>continuous glucose monitoring</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes, Gestational</mesh_term>
    <mesh_term>Diabetes Mellitus</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02244814
org study id: 14-1358
nct id: NCT02244814
lead sponsor: 
collaborator: 
has dmc: No
The rapidly rising risk of gestational diabetes pregnant women demands that an effective diet
      strategy be developed due to the high risk of fetal overgrowth, which places the newborn at
      increased risk for childhood obesity and metabolic syndrome. The aims of this randomized
      clinical trial are to compare the effects of an 8-wk isocaloric higher complex
      carbohydrate/lower fat diet vs. a conventional lower carbohydrate (higher fat) diet on
      glycemic and lipid profiles, maternal insulin resistance, placenta nutrient transporters, the
      maternal microbiome, neonatal intrahepatic fat, and neonatal total adiposity (primary
      outcome). The investigators will then follow the infants for 1-yr and measure maternal breast
      milk and infant microbiome composition to observe if they impact net fat mass gain
      differently in infants exposed to one diet vs. the other. Identifying a diet for gestational
      diabetes mellitus women that can effectively alter maternal/fetal metabolism is critical to
      reducing short- and long-term metabolic risk in this growing cohort of mothers and infants
      and has the potential to be applicable to overweight/obese pregnant women.
The rapidly rising incidence of gestational diabetes mellitus in overweight/obese pregnant
      women demands that an effective diet strategy be developed due to the high risk of fetal
      overgrowth, which places the newborn at increased risk for childhood obesity and metabolic
      syndrome. However, the lack of adequate controlled randomized clinical trials for treatment
      of gestational diabetes with diet has resulted in consensus panels abandoning any specific
      diet recommendation. If effective, diet therapy has the potential to avoid the high costs of
      medical treatment and intensified fetal monitoring for this growing population. Although a
      low carbohydrate diet has historically been advocated to decrease glucose excursions after
      meals, carbohydrate has typically been replaced by higher fat which has been shown in animal
      and non-human primate data to promote insulin resistance, glucose intolerance, and liver fat
      deposition in the offspring. In fact, recent human data suggest that high maternal
      triglycerides and free fatty acids, variables sensitive to dietary manipulation, may be at
      least as important as glucose in contributing to excess fetal growth and infant adiposity.
      Preliminary data based on an R21, show that compared to a conventional lower-carbohydrate
      (higher in fat) diet, providing a higher complex carbohydrate (lower fat) diet effectively
      blunts postprandial glucose and improves fasting glucose and insulin after 6-7 weeks, with
      less adiposity in the newborn. The investigators global hypothesis is that compared to 8
      weeks of a low-carbohydrate/higher fat diet, a higher complex carbohydrate/lower fat diet
      will blunt maternal post-prandial free fatty acids and improve insulin resistance. Improved
      insulin sensitivity will reduce fetal over-nutrition by decreasing substrate availability and
      down-regulating placental nutrient transporters, thereby reducing neonatal adiposity (primary
      outcome).This proposal builds on the investigators R21 study, which is the first randomized
      clinical trial to provide all meals from the time of gestational diabetes diagnosis
      throughout the remainder of pregnancy. The aims of this randomized trial are to compare the
      effects of an 8-wk isocaloric higher complex carbohydrate/lower fat diet (60%
      carbohydrate/25% fat) vs. a conventional low-carbohydrate (higher fat)(40% carbohydrate/45%
      fat) diet on maternal insulin resistance, placental nutrient transporters, and neonatal fat
      development. Innovative approaches by the investigators skilled multidisciplinary team
      include: maternal insulin resistance systemically (oral glucose tolerance Index) and locally
      (adipose tissue lipolysis); intestinal microbiome (transferred to the newborn); and neonatal
      intrahepatic fat (magnetic resonance spectroscopy). Persistence of neonatal adiposity is
      relevant to understanding obesity risk in these infants. As the investigators pilot data
      suggest infant microbiome and breast milk composition impact fat accrual after birth, the
      investigators will follow the infants through 1-yr of life accounting for these variables.
      Identifying a diet for gestational diabetes that can effectively alter maternal/fetal
      metabolism in late pregnancy when fetal growth accelerates is critical to reducing short- and
      long-term metabolic risk in this growing cohort of mothers and infants. The study results
      could lead to a paradigm shift for diet therapy in gestational diabetes, with potential
      widespread application to pregnancies affected by obesity alone.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Neonatal adiposity
time frame: 5-7 days after birth
description: Air-displacement plethysmography
measure: Maternal Insulin Resistance
time frame: 36 wks gestation
description: Between-diet difference in post-prandial free fatty acid area-under-the-curve as a surrogate for insulin resistance
measure: Placental fatty acid transporter protein-2 expression
time frame: Delivery
description: Between diet-difference in protein expression of placental fatty acid transporter protein-2.
measure: Oral glucose tolerance test
time frame: Baseline, 36 wks
description: 75g oral glucose tolerance test; calculated Index to assess diet-induced differences in maternal insulin resistance.
measure: Adipose Tissue Lipolysis
time frame: Baseline, 36 wks
description: Diet-induced difference in adipose tissue lipolysis.
measure: Infant Adiposity
time frame: Birth-12 mos
description: Infant adiposity (air displacement plethysmography, anthropometry) from delivery - 1 year (dual x-ray absorptiometry)
arm group label: Choosing Healthy Options in Carbohydrate Energy
arm group type: Experimental
description: 60% carbohydrate/25% fat/15% protein diet
arm group label: Low Carbohydrate/Conventional
arm group type: Active Comparator
description: 40% carbohydrate/45% fat/15% protein
intervention type: Behavioral
intervention name: Low Carbohydrate/Conventional
description: Lower-carbohydrate/conventional diet (usual care)
arm group label: Choosing Healthy Options in Carbohydrate Energy
arm group label: Low Carbohydrate/Conventional
intervention type: Behavioral
intervention name: Choosing Healthy Options in Carbohydrate Energy
description: Choosing Healthy Options in Carbohydrate Energy
arm group label: Choosing Healthy Options in Carbohydrate Energy
arm group label: Low Carbohydrate/Conventional
criteria: 
gender: All
minimum age: N/A
maximum age: 36 Years
healthy volunteers: No
last name: Teri L Hernandez, PhD, RN
role: Principal Investigator
affiliation: University of Colorado, Denver
facility: 
country: United States
citation: Hernandez TL, Van Pelt RE, Anderson MA, Daniels LJ, West NA, Donahoo WT, Friedman JE, Barbour LA. A higher-complex carbohydrate diet in gestational diabetes mellitus achieves glucose targets and lowers postprandial lipids: a randomized crossover study. Diabetes Care. 2014;37(5):1254-62. doi: 10.2337/dc13-2411. Epub 2014 Mar 4.
PMID: 24595632
responsible party type: Sponsor
mesh term: Diabetes, Gestational
mesh term: Diabetes Mellitus
sharing ipd: No