Clinical trial NCT01926457: Treating Prediabetes in the First Trimester
Official title: Treating Prediabetes in the First Trimester: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prediabetes
Gestational Diabetes
Keywords: First trimester treatment of prediabetes
First trimester treatment of gestational diabetes
Umbilical cord C-Peptide
Neonatal fat mass
Gestational weight gain
Infant obesity
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: American College of Obstetricians and Gynecologists
name: Society for Maternal-Fetal Medicine
First posted: 2013-08-21
Enrollment: 202
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators plan to study a sample of women with prediabetes (diagnosed by Hemoglobin A1c (HbA1c) 5.7-6.4% or fasting plasma glucose (FPG) 92-125 mg/dL) in the first trimester of pregnancy, and patients will be randomized to first trimester or third trimester treatment; the first trimester group will receive intervention immediately upon diagnosis of prediabetes whereas the third trimester group will receive only routine prenatal care until 28 weeks at which time they will receive intervention.

Intervention is defined as:

* diabetes education
* blood glucose monitoring
* medications as needed
* growth ultrasounds
* antenatal testing

The primary outcome is umbilical cord C-Peptide \>90th percentile. Secondary outcomes include neonatal fat mass at delivery, infant weight-for-length at 12 months of age, maternal gestational weight gain, and biomarkers (chemicals) measured in the placenta and the baby's umbilical cord blood.

The investigators hypothesize that women who undergo the above intervention in the first trimester will deliver significantly fewer neonates with umbilical cord C-Peptide \>90th percentile, and that the neonates will have lower fat mass, and weight-for-length at 12 months. The investigators further hypothesize that a greater proportion of patients undergoing first trimester intervention will have appropriate maternal gestational weight gain as defined by the Institute of Medicine, and a greater proportion will return to prepregnancy weight within 12 months.

Detailed description: The primary aim of the proposed research is to demonstrate that promoting a normoglycemic intrauterine milieu in women with prediabetes diagnosed in the first trimester of pregnancy with a Hemoglobin A1c (HbA1c) 5.7-6.4% or fasting plasma glucose (FPG) 92-125 mg/dL will decrease the accumulation of fetal white adipose tissue and development of infant/child obesity during the first year of life. This project is built upon the hypothesis that pregnant subjects with prediabetes randomized in the first trimester of pregnancy to strict glycemic control and pharmacotherapy as needed will have less fetal adiposity and adverse neonatal outcomes than those who receive the diagnosis of prediabetes but do not initiate care until the third trimester.

In the proposed study, 240 women meeting the above criteria for prediabetes at ≤ 15w0d gestation will be randomized to either first trimester or third trimester treatment. Each group will have diabetes education, initiate blood glucose monitoring, begin pharmacotherapy as needed (per established protocol), undergo growth ultrasounds, and antenatal testing. The first trimester arm will receive the above interventions immediately upon diagnosis of prediabetes whereas the third trimester arm will receive only routine prenatal care until 28 weeks at which time they will begin education and treatment. Both groups will be treated identically from 28 weeks until delivery.

In the 2013 the National Institutes of Health (NIH) Gestational Diabetes (GDM) Consensus Conference, the panel was concerned about adopting criteria that would increase prevalence of GDM (i.e. first trimester treatment) without first demonstrating improved outcomes. The results of this proposed trial, will allow us to fill key research gaps; this is the first prospective trial to evaluate the International Associations of Diabetes in Pregnancy Study Groups (IADPSG) recommendations for screening and diagnosing prediabetes in the first trimester.

Findings from this research will quantify the maternal and neonatal benefits and harms of treating women with prediabetes from early pregnancy. Additionally, the cohort of neonates that will result from this study can be followed into childhood to evaluate whether first trimester treatment has benefits beyond those anticipated at birth and may decrease the long-term incidence of obesity and diabetes.

Eligibility criteria: Inclusion Criteria:

* Pregnant women age 18 and above
* Any ethnic background
* English- or Spanish-speaking
* Planned prenatal care/delivery at The University of California, San Diego's Hillcrest Hospital
* Singleton pregnancy
* Prediabetes diagnosed prior to 15w0d with HbA1c 5.7-6.4% or FPG 92-125 mg/dL

Exclusion Criteria:

* Known Type 2 Diabetes (T2DM)
* T2DM diagnosed with first trimester screening
* Patients with known maternal/fetal indications for delivery \<36w0d
* Patients presenting for care after 15w0d

Primary outcomes:
measure: Umbilical Cord C-Peptide >90th percentile
timeFrame: 1 day (Collected at the time of delivery)
Secondary outcomes:
measure: Neonatal fat mass
timeFrame: Within 48 hours of delivery
measure: Adherence to the Institute of Medicine (IOM) guidelines for gestational weight gain
timeFrame: Weight gain will be measured from immediately preconception until delivery
measure: Return to prepregnancy weight
timeFrame: After 1 year post delivery
Other outcomes:
measure: birthweight
timeFrame: At delivery
measure: birthweight percentile
timeFrame: At delivery
measure: Infant gender
timeFrame: At delivery
measure: Ponderal index
timeFrame: At delivery
measure: Neonatal Intensive Care Unit (NICU) Admission
timeFrame: Within 10 days after birth
measure: Infant weight-for-length
timeFrame: 6 months and 12 months after delivery
measure: Need for pharmacotherapy to control hyperglycemia
timeFrame: From 5 weeks gestation until time of delivery
measure: Birth trauma
timeFrame: At delivery
measure: Mode of delivery
timeFrame: At delivery
measure: Indication for delivery
timeFrame: At delivery
measure: Total gestational weight gain
timeFrame: From immediately preconception until delivery
measure: Postpartum weight retention
timeFrame: Within 1 year of delivery
measure: Diagnosis of Preeclampsia
timeFrame: From 20 weeks gestation until 6 weeks postpartum
Locations:
city: San Diego
country: United States
facility: UC San Diego Health System
state: California
Study officials:
affiliation: UC San Diego Health System
name: Hilary A Roeder, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UC San Diego Health System
name: Gladys A Ramos, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UC San Diego Health System
name: Thomas R Moore, MD
role: PRINCIPAL_INVESTIGATOR
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