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Maternal Metabolic and Molecular Changes Induced by Preconception Weight Loss and Their Effects on Birth Outcomes

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ClinicalTrials.gov Identifier: NCT03244722
Recruitment Status : Recruiting
First Posted : August 9, 2017
Last Update Posted : December 28, 2021
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Amy E Rothberg, University of Michigan

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Obesity; Familial Pregnancy Related Dietary Supplement: Very-low energy Diet (VLED) Other: Standard of care (SOC) Not Applicable

Detailed Description:
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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 352 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Maternal Metabolic and Molecular Changes Induced by Preconception Weight Loss and Their Effects on Birth Outcomes
Actual Study Start Date : April 10, 2018
Estimated Primary Completion Date : August 31, 2025
Estimated Study Completion Date : August 31, 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Obese - Very low energy diet (VLED)
Participants will adopt a very-low energy diet
Dietary Supplement: Very-low energy Diet (VLED)
Structured, intensive dietary intervention using liquid meal replacements aimed at providing 800 kcal/day with a weight loss goal of 15% from baseline

Obese - Standard of care (SOC)
Participants will receive the standard of care for obese women looking to become pregnant.
Other: Standard of care (SOC)
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

Lean - Standard of care (SOC)
Participants will receive the standard of care for lean women looking to become pregnant.
Other: Standard of care (SOC)
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




Primary Outcome Measures :
  1. Preconception weight loss [ Time Frame: Baseline to post dietary intervention (16 weeks) ]
    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).

  2. Metabolome and inflammatory markers [ Time Frame: Delivery ]
    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).

  3. Offspring body fat mass [ Time Frame: Delivery ]
    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).

  4. Cord blood related to neonate outcomes [ Time Frame: Before and after dietary intervention (16 weeks), delivery ]
    The maternal metabolome (~metabolites) will be related to neonate adiposity, gestational weight gain, pregnancy complications, and intrauterine fetal growth rate.

  5. DNA methylation [ Time Frame: Delivery ]
    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.


Secondary Outcome Measures :
  1. 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) ]
    The change in waist circumference (cm) will be assessed using a retractable, soft nylon measuring tape.

  2. 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) ]
    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.

  3. Infant length and weight [ Time Frame: Delivery to 12 month follow-up ]
    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.

  4. Metabolite levels [ Time Frame: Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks), delivery ]
    Relationships between metabolite levels (~2000 metabolites) in maternal blood at each trimester and cord blood mononuclear cell DNA methylation will be compared


Other Outcome Measures:
  1. Mode of delivery [ Time Frame: Delivery ]
    Categorical as caesarean or vaginal delivery

  2. Fetal growth abnormalities [ Time Frame: Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks) ]
    Categorical as miscarriage, intrauterine growth restriction (IUGR), fetal demise, fetal anomalies

  3. Maternal diagnosis [ Time Frame: Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks), delivery ]
    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.



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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • BMI > 30 ≤ 45 for obese participants OR
  • BMI ≤ 25 for healthy body weight participants
  • No known infertility
  • No known risk factors for tubal disease

Exclusion Criteria:

  • Significant medical co-morbidities (e.g. heart, kidney, liver, autoimmune disease)
  • Significant anemia
  • Cancer other than minor skin cancers
  • Conditions that would complicate pregnancy
  • Recent use of anti-obesity drugs or appetite suppressants
  • Previous bariatric surgery
  • Endometriosis AFS (American Fertility Society classification class III or IV)
  • Progesterone > 10 IU/ml
  • Current pregnancy
  • Use of sperm donor

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03244722


Contacts
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Contact: Shannon Considine, MPH, MSW 734-232-6483 sconsidi@umich.edu

Locations
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United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48106
Contact: Shannon Considine, MPH, MSW         
Sponsors and Collaborators
University of Michigan
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Amy Rothberg, MD, PhD University of Michigan
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Responsible Party: Amy E Rothberg, Project Investigator, University of Michigan
ClinicalTrials.gov Identifier: NCT03244722    
Other Study ID Numbers: HUM00124673
1R01DK124862 ( U.S. NIH Grant/Contract )
First Posted: August 9, 2017    Key Record Dates
Last Update Posted: December 28, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Weight Loss
Body Weight Changes
Body Weight