Metabolic Analysis for Treatment Choice in Gestational Diabetes Mellitus

Study Overview
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Brief Summary
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Gestational diabetes (GDM) is a significant clinical and public health burden, affecting over 400,000 pregnant women in the United States each year. Without adequate treatment, women with GDM and their infants are at risk for substantial morbidity. Because of this, experts recommend treatment focused on normalization of hyperglycemia to improve outcomes. However, providers have limited capacity to predict which treatment will achieve glycemic goals. This results in a choice based on provider and patient preference and a trial and error approach, which can create delays in glycemic control within the short (8-10 weeks) window between diagnosis and delivery. Maternal and fetal morbidity may be related to a mismatch between glycemic pathophysiology and the mechanism of action of glucose-lowering agents. In fact, GDM is heterogeneous, with predominant insulin resistance (IR) in 50%, insulin secretion deficit (ISD) in 30%, and a combination of both in 20% of women as underlying mechanisms of hyperglycemia. This variation in GDM pathophysiology and clinical outcomes supports the use of an individualized treatment approach. The overall goal of this project is to investigate an individualized treatment approach for GDM where treatment is based on each woman's GDM mechanism. The study will employ the same treatment in both arms, but choice of treatment will differ based on study arm (matched or unmatched to GDM mechanism).

Official Title
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Metabolic Analysis for Treatment Choice in Gestational Diabetes Mellitus

Conditions
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Gestational Diabetes, Diabetes, Gestational, Pregnancy in Diabetes

Intervention / Treatment
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* Drug: Insulin
* Drug: Glyburide
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women beyond 24 weeks of gestation who are scheduled for a 3-hour oral glucose tolerance test. Exclusion Criteria: Fetal anomaly Pregestational diabetes GDM diagnosis without a 3-hour OGTT Multifetal gestation Treatment with non-inhaled steroids within 7 days Allergy to glyburide, metformin or sulfa History of severe pulmonary (pulmonary requirement for oxygen therapy or daily treatment for restrictive of obstructive pulmonary disease) Hepatic (LFT's greater than two times of upper normal range) Renal (serum creatinine higher than 1.2 mg/dL) disease History of heart failure or myocardial infarction

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Pilot randomized controlled study
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Usual Care<br>Participants will undergo standard counseling and be prescribed a treatment for their GDM. Treatments include insulin, glyburide, and metformin. | Drug: Insulin<br>* Insulin will be used for GDM treatment<br>Drug: Glyburide<br>* Glyburide will be used for GDM treatment<br>Drug: Metformin<br>* Metformin will be used for GDM treatment<br>|
| Active Comparator: Individualized Treatment<br>Participants will undergo standard counseling and be matched to therapy based on their GDM mechanism. Treatments include insulin, glyburide, and metformin. | Drug: Insulin<br>* Insulin will be used for GDM treatment<br>Drug: Glyburide<br>* Glyburide will be used for GDM treatment<br>Drug: Metformin<br>* Metformin will be used for GDM treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of women who are eligible, screened, enroll and remain in the study |  | Through study completion, an average of 16 weeks | 
| Proportion of participants who report suitability of the study procedures | Suitability of the study procedures and interventions to participants assessed through one-on-one qualitative interview | Through study completion, an average of 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with consistent GDM mechanism before and and after treatment initiation |  | 2 weeks after treatment initiation | 
| Proportion of women who remain on same treatment during study |  | Through study completion, an average of 16 weeks | 
| Maternal glucose control |  | Delivery | 
| Proportion of participants who deliver by primary cesarean |  | Delivery | 
| Proportion of participants who developed hypertensive diseases in pregnancy |  | Delivery | 
| Birthweight |  | Delivery | 
| Neonatal lean body mass |  | Within 72 hours of delivery | 
| Cord blood glucose |  | Delivery | 
| Cord blood c-peptide |  | Delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gestational diabetes, Diabetes in pregnancy, Insulin resistance, Insulin secretion deficiency