<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/NCT03244722</url>
  </required_header>
  <id_info>
    <org_study_id>HUM00124673</org_study_id>
    <secondary_id>1R01DK124862</secondary_id>
    <nct_id>NCT03244722</nct_id>
  </id_info>
  <brief_title>Maternal Metabolic and Molecular Changes Induced by Preconception Weight Loss and Their Effects on Birth Outcomes</brief_title>
  <official_title>Maternal Metabolic and Molecular Changes Induced by Preconception Weight Loss and Their Effects on Birth Outcomes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Michigan</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Our hypothesis is that aggressive preconception weight loss in obese women will improve the&#xD;
      metabolic health of the mother and the intrauterine environment. An optimized developmental&#xD;
      environment will normalize fetal growth and improve clinical fetal and infant outcomes, and&#xD;
      theoretically reduce future susceptibility to obesity and cardiometabolic disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Further, our hypothesis is that the metabolic profiles in the mother and infant cord blood&#xD;
      and epigenetic profiles in cord blood leukocytes will be improved in the very-low energy diet&#xD;
      (VLED) group compared to standard practice nutrition counseling and support (SOC) group and&#xD;
      approach the profiles found in normal weight (LEAN) individuals. We will relate these changes&#xD;
      to the changes in the offspring clinical profiles. With these data in hand, we will develop a&#xD;
      model to understand the potential molecular markers associated with offspring size and&#xD;
      adiposity at birth, risk factors for later onset non-communicable diseases. We will use these&#xD;
      insights to define, adopt and implement future interventions that mitigate the downstream&#xD;
      risk of adiposity and cardiometabolic diseases.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 10, 2018</start_date>
  <completion_date type="Anticipated">August 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2025</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Preconception weight loss</measure>
    <time_frame>Baseline to post dietary intervention (16 weeks)</time_frame>
    <description>Primary pre-specified outcome is BMI change (kg/m2) after dietary intervention. Trained staff will measure height and weight to the nearest .1cm and .1kg using a wall-mounted, precision stadiometer and calibrated digital scale. BMI will be calculated (kg/m2).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Metabolome and inflammatory markers</measure>
    <time_frame>Delivery</time_frame>
    <description>Multivariate computational models will assess the association of maternal and neonate metabolite and inflammatory markers to fetal growth and newborn weight (g) and adiposity (g).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Offspring body fat mass</measure>
    <time_frame>Delivery</time_frame>
    <description>Percentage body fat (adiposity) in the offspring of women randomized to Very Low Energy Diet (VLED) compared to those randomized to Standard of Care (SOC). Body composition will be assessed by PeaPod (fat mass in grams).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cord blood related to neonate outcomes</measure>
    <time_frame>Before and after dietary intervention (16 weeks), delivery</time_frame>
    <description>The maternal metabolome (~metabolites) will be related to neonate adiposity, gestational weight gain, pregnancy complications, and intrauterine fetal growth rate.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>DNA methylation</measure>
    <time_frame>Delivery</time_frame>
    <description>Differences in site-specific DNA methylation (~450,000 sites) in offspring cord blood mononuclear cells between the Standard of Care (SOC), Very Low Energy Diet (VLED) and lean groups will be assessed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Participant waist circumference in centimeters</measure>
    <time_frame>Baseline and post dietary intervention (16 weeks), each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks)</time_frame>
    <description>The change in waist circumference (cm) will be assessed using a retractable, soft nylon measuring tape.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fetal growth will be assessed by ultrasound</measure>
    <time_frame>Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks)</time_frame>
    <description>Gestational sac dimensions (mm), fundal height (mm), biparietal diameter (mm), head circumference (mm), and waist circumference (mm) will be assessed through ultrasound to determine fetal growth.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infant length and weight</measure>
    <time_frame>Delivery to 12 month follow-up</time_frame>
    <description>Trained staff will measure infant length and weight to the nearest .1cm and .1kg using an infant length board and digital infant scale at delivery, 2-, 4-, 6-, 9-, and 12-months. Ponderal index will be calculated and used to assess change in growth.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolite levels</measure>
    <time_frame>Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks), delivery</time_frame>
    <description>Relationships between metabolite levels (~2000 metabolites) in maternal blood at each trimester and cord blood mononuclear cell DNA methylation will be compared</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Mode of delivery</measure>
    <time_frame>Delivery</time_frame>
    <description>Categorical as caesarean or vaginal delivery</description>
  </other_outcome>
  <other_outcome>
    <measure>Fetal growth abnormalities</measure>
    <time_frame>Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks)</time_frame>
    <description>Categorical as miscarriage, intrauterine growth restriction (IUGR), fetal demise, fetal anomalies</description>
  </other_outcome>
  <other_outcome>
    <measure>Maternal diagnosis</measure>
    <time_frame>Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks), delivery</time_frame>
    <description>Categorical as maternal cardiac dysfunction, maternal proteinuria, maternal sleep apnea, fatty liver disease, gestational diabetes, preeclampsia, indicated preterm birth date, failed trial of labor, endometritis, venous thrombosis, COVD-19, surgical wound complications, postpartum anemia, postpartum depression, early termination of breastfeeding.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">352</enrollment>
  <condition>Obesity; Familial</condition>
  <condition>Pregnancy Related</condition>
  <arm_group>
    <arm_group_label>Obese - Very low energy diet (VLED)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants will adopt a very-low energy diet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Obese - Standard of care (SOC)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants will receive the standard of care for obese women looking to become pregnant.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lean - Standard of care (SOC)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants will receive the standard of care for lean women looking to become pregnant.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Very-low energy Diet (VLED)</intervention_name>
    <description>Structured, intensive dietary intervention using liquid meal replacements aimed at providing 800 kcal/day with a weight loss goal of 15% from baseline</description>
    <arm_group_label>Obese - Very low energy diet (VLED)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard of care (SOC)</intervention_name>
    <description>Standard consultation with registered dietitian to determine appropriate caloric deficit for a low calorie diet, education and advice to achieve weight loss in obese women. Standard of care for normal weight women</description>
    <arm_group_label>Lean - Standard of care (SOC)</arm_group_label>
    <arm_group_label>Obese - Standard of care (SOC)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  BMI &gt; 30 ≤ 45 for obese participants OR&#xD;
&#xD;
          -  BMI ≤ 25 for healthy body weight participants&#xD;
&#xD;
          -  No known infertility&#xD;
&#xD;
          -  No known risk factors for tubal disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Significant medical co-morbidities (e.g. heart, kidney, liver, autoimmune disease)&#xD;
&#xD;
          -  Significant anemia&#xD;
&#xD;
          -  Cancer other than minor skin cancers&#xD;
&#xD;
          -  Conditions that would complicate pregnancy&#xD;
&#xD;
          -  Recent use of anti-obesity drugs or appetite suppressants&#xD;
&#xD;
          -  Previous bariatric surgery&#xD;
&#xD;
          -  Endometriosis AFS (American Fertility Society classification class III or IV)&#xD;
&#xD;
          -  Progesterone &gt; 10 IU/ml&#xD;
&#xD;
          -  Current pregnancy&#xD;
&#xD;
          -  Use of sperm donor&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Amy Rothberg, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Shannon Considine, MPH, MSW</last_name>
    <phone>734-232-6483</phone>
    <email>sconsidi@umich.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48106</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Shannon Considine, MPH, MSW</last_name>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>August 5, 2017</study_first_submitted>
  <study_first_submitted_qc>August 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 9, 2017</study_first_posted>
  <last_update_submitted>September 1, 2023</last_update_submitted>
  <last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Michigan</investigator_affiliation>
    <investigator_full_name>Amy E Rothberg</investigator_full_name>
    <investigator_title>Project Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Weight Loss</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/NCT03244722
org study id: HUM00124673
secondary id: 1R01DK124862
nct id: NCT03244722
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Our hypothesis is that aggressive preconception weight loss in obese women will improve the
      metabolic health of the mother and the intrauterine environment. An optimized developmental
      environment will normalize fetal growth and improve clinical fetal and infant outcomes, and
      theoretically reduce future susceptibility to obesity and cardiometabolic disease.
Further, our hypothesis is that the metabolic profiles in the mother and infant cord blood
      and epigenetic profiles in cord blood leukocytes will be improved in the very-low energy diet
      (VLED) group compared to standard practice nutrition counseling and support (SOC) group and
      approach the profiles found in normal weight (LEAN) individuals. We will relate these changes
      to the changes in the offspring clinical profiles. With these data in hand, we will develop a
      model to understand the potential molecular markers associated with offspring size and
      adiposity at birth, risk factors for later onset non-communicable diseases. We will use these
      insights to define, adopt and implement future interventions that mitigate the downstream
      risk of adiposity and cardiometabolic diseases.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Preconception weight loss
time frame: Baseline to post dietary intervention (16 weeks)
description: Primary pre-specified outcome is BMI change (kg/m2) after dietary intervention. Trained staff will measure height and weight to the nearest .1cm and .1kg using a wall-mounted, precision stadiometer and calibrated digital scale. BMI will be calculated (kg/m2).
measure: Metabolome and inflammatory markers
time frame: Delivery
description: Multivariate computational models will assess the association of maternal and neonate metabolite and inflammatory markers to fetal growth and newborn weight (g) and adiposity (g).
measure: Offspring body fat mass
time frame: Delivery
description: Percentage body fat (adiposity) in the offspring of women randomized to Very Low Energy Diet (VLED) compared to those randomized to Standard of Care (SOC). Body composition will be assessed by PeaPod (fat mass in grams).
measure: Cord blood related to neonate outcomes
time frame: Before and after dietary intervention (16 weeks), delivery
description: The maternal metabolome (~metabolites) will be related to neonate adiposity, gestational weight gain, pregnancy complications, and intrauterine fetal growth rate.
measure: DNA methylation
time frame: Delivery
description: Differences in site-specific DNA methylation (~450,000 sites) in offspring cord blood mononuclear cells between the Standard of Care (SOC), Very Low Energy Diet (VLED) and lean groups will be assessed.
measure: Participant waist circumference in centimeters
time frame: Baseline and post dietary intervention (16 weeks), each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks)
description: The change in waist circumference (cm) will be assessed using a retractable, soft nylon measuring tape.
measure: Fetal growth will be assessed by ultrasound
time frame: Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks)
description: Gestational sac dimensions (mm), fundal height (mm), biparietal diameter (mm), head circumference (mm), and waist circumference (mm) will be assessed through ultrasound to determine fetal growth.
measure: Infant length and weight
time frame: Delivery to 12 month follow-up
description: Trained staff will measure infant length and weight to the nearest .1cm and .1kg using an infant length board and digital infant scale at delivery, 2-, 4-, 6-, 9-, and 12-months. Ponderal index will be calculated and used to assess change in growth.
measure: Metabolite levels
time frame: Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks), delivery
description: Relationships between metabolite levels (~2000 metabolites) in maternal blood at each trimester and cord blood mononuclear cell DNA methylation will be compared
measure: Mode of delivery
time frame: Delivery
description: Categorical as caesarean or vaginal delivery
measure: Fetal growth abnormalities
time frame: Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks)
description: Categorical as miscarriage, intrauterine growth restriction (IUGR), fetal demise, fetal anomalies
measure: Maternal diagnosis
time frame: Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks), delivery
description: Categorical as maternal cardiac dysfunction, maternal proteinuria, maternal sleep apnea, fatty liver disease, gestational diabetes, preeclampsia, indicated preterm birth date, failed trial of labor, endometritis, venous thrombosis, COVD-19, surgical wound complications, postpartum anemia, postpartum depression, early termination of breastfeeding.
arm group label: Obese - Very low energy diet (VLED)
arm group type: Other
description: Participants will adopt a very-low energy diet
arm group label: Obese - Standard of care (SOC)
arm group type: Other
description: Participants will receive the standard of care for obese women looking to become pregnant.
arm group label: Lean - Standard of care (SOC)
arm group type: Other
description: Participants will receive the standard of care for lean women looking to become pregnant.
intervention type: Dietary Supplement
intervention name: Very-low energy Diet (VLED)
description: Structured, intensive dietary intervention using liquid meal replacements aimed at providing 800 kcal/day with a weight loss goal of 15% from baseline
arm group label: Obese - Very low energy diet (VLED)
intervention type: Other
intervention name: Standard of care (SOC)
description: Standard consultation with registered dietitian to determine appropriate caloric deficit for a low calorie diet, education and advice to achieve weight loss in obese women. Standard of care for normal weight women
arm group label: Lean - Standard of care (SOC)
arm group label: Obese - Standard of care (SOC)
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Amy Rothberg, MD, PhD
role: Principal Investigator
affiliation: University of Michigan
last name: Shannon Considine, MPH, MSW
phone: 734-232-6483
email: sconsidi@umich.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Michigan
investigator full name: Amy E Rothberg
investigator title: Project Investigator
mesh term: Weight Loss
sharing ipd: No