Clinical trial NCT03244722: Maternal Metabolic and Molecular Changes Induced by Preconception Weight Loss and Their Effects on Birth Outcomes
Official title: Maternal Metabolic and Molecular Changes Induced by Preconception Weight Loss and Their Effects on Birth Outcomes
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Obesity; Familial
Pregnancy Related
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2017-08-09
Enrollment: 352
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility 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

Primary outcomes:
measure: Preconception weight loss
timeFrame: Baseline to post dietary intervention (16 weeks)
measure: Metabolome and inflammatory markers
timeFrame: Delivery
measure: Offspring body fat mass
timeFrame: Delivery
measure: Cord blood related to neonate outcomes
timeFrame: Before and after dietary intervention (16 weeks), delivery
measure: DNA methylation
timeFrame: Delivery
Secondary outcomes:
measure: Participant waist circumference in centimeters
timeFrame: Baseline and post dietary intervention (16 weeks), each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks)
measure: Fetal growth will be assessed by ultrasound
timeFrame: Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks)
measure: Infant length and weight
timeFrame: Delivery to 12 month follow-up
measure: Metabolite levels
timeFrame: Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks), delivery
Other outcomes:
measure: Mode of delivery
timeFrame: Delivery
measure: Fetal growth abnormalities
timeFrame: Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks)
measure: Maternal diagnosis
timeFrame: Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks), delivery
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: Amy Rothberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: