Diabetes, Gestational, Gestational Diabetes, Pregnancy in Diabetes
Conditions
Keywords
Gestational diabetes, Diabetes in pregnancy, Insulin resistance, Insulin secretion deficiency
Brief summary
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).
Interventions
DRUGInsulin
Insulin will be used for GDM treatment
DRUGGlyburide
Glyburide will be used for GDM treatment
DRUGMetformin
Metformin will be used for GDM treatment
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Maisa N. Feghali, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Study team members assessing delivery outcomes will be masked to the participant's study assignment
Intervention model description
Pilot randomized controlled study
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Women Who Are Eligible, Screened, Enroll and Remain in the Study | Through study completion, an average of 16 weeks | Proportion of women who are eligible, screened, enrolled and remain in the study |
| Proportion of Participants Who Report Suitability of the Study Procedures | Through study completion, an average of 16 weeks | Suitability of the study procedures and interventions to participants assessed through one-on-one qualitative interview |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maternal Glucose Control | Delivery | \>50% fasting below 95 and 1 hour postprandial \< 140 during the 4 weeks before delivery |
| Proportion of Participants Who Deliver by Primary Cesarean | Delivery | — |
| Proportion of Participants Who Developed Hypertensive Diseases in Pregnancy | Delivery | — |
| Proportion of Participants With Consistent GDM Mechanism Before and and After Treatment Initiation | 2 weeks after treatment initiation | — |
| Neonatal Lean Body Mass | Within 72 hours of delivery | — |
| Cord Blood Glucose | Delivery | — |
| Cord Blood C-peptide | Delivery | — |
| Birthweight | Delivery | — |
| Proportion of Women Who Remain on Same Treatment During Study | Through study completion, an average of 16 weeks | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Usual Care Participants will undergo standard counseling and be prescribed a treatment for their GDM. Treatments include insulin, glyburide, and metformin.
Insulin: Insulin will be used for GDM treatment
Glyburide: Glyburide will be used for GDM treatment
Metformin: Metformin will be used for GDM treatment | 27 |
| Individualized Treatment Participants will undergo standard counseling and be matched to therapy based on their GDM mechanism. Treatments include insulin, glyburide, and metformin.
Insulin: Insulin will be used for GDM treatment
Glyburide: Glyburide will be used for GDM treatment
Metformin: Metformin will be used for GDM treatment | 27 |
| Total | 54 |
Baseline characteristics
| Characteristic | Individualized Treatment | Total | Usual Care |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 54 Participants | 27 Participants |
| Age, Continuous | 30.91 years STANDARD_DEVIATION 6.6 | 30.9 years STANDARD_DEVIATION 6.2 | 30.90 years STANDARD_DEVIATION 5.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 14 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 13 Participants | 27 Participants | 14 Participants |
| Region of Enrollment United States | 27 participants | 54 participants | 27 participants |
| Sex: Female, Male Female | 27 Participants | 54 Participants | 27 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 27 |
| other Total, other adverse events | 0 / 27 | 0 / 27 |
| serious Total, serious adverse events | 0 / 27 | 0 / 27 |
Outcome results
Primary
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
Time frame: Through study completion, an average of 16 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Proportion of Participants Who Report Suitability of the Study Procedures | 24 Participants |
| Individualized Treatment | Proportion of Participants Who Report Suitability of the Study Procedures | 25 Participants |
p-value: 0.8Fisher Exact
Primary
Proportion of Women Who Are Eligible, Screened, Enroll and Remain in the Study
Proportion of women who are eligible, screened, enrolled and remain in the study
Time frame: Through study completion, an average of 16 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Proportion of Women Who Are Eligible, Screened, Enroll and Remain in the Study | 25 Participants |
| Individualized Treatment | Proportion of Women Who Are Eligible, Screened, Enroll and Remain in the Study | 26 Participants |
p-value: 0.9Fisher Exact
Secondary
Birthweight
Time frame: Delivery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Birthweight | 332.5 g | Standard Deviation 376.7 |
| Individualized Treatment | Birthweight | 3445.4 g | Standard Deviation 627.2 |
p-value: 0.7t-test, 2 sided
Secondary
Cord Blood C-peptide
Time frame: Delivery
Population: Samples unavailable for analysis due to freezer storage malfunction
Secondary
Cord Blood Glucose
Time frame: Delivery
Population: Samples unavailable for analysis due to freezer storage malfunction
Secondary
Maternal Glucose Control
\>50% fasting below 95 and 1 hour postprandial \< 140 during the 4 weeks before delivery
Time frame: Delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Maternal Glucose Control | 20 Participants |
| Individualized Treatment | Maternal Glucose Control | 22 Participants |
p-value: 0.8Fisher Exact
Secondary
Neonatal Lean Body Mass
Time frame: Within 72 hours of delivery
Population: Unable to collect neonatal data due to lack of staffing availability
Secondary
Proportion of Participants Who Deliver by Primary Cesarean
Time frame: Delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Proportion of Participants Who Deliver by Primary Cesarean | 9 Participants |
| Individualized Treatment | Proportion of Participants Who Deliver by Primary Cesarean | 11 Participants |
p-value: 0.6Chi-squared
Secondary
Proportion of Participants Who Developed Hypertensive Diseases in Pregnancy
Time frame: Delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Proportion of Participants Who Developed Hypertensive Diseases in Pregnancy | 4 Participants |
| Individualized Treatment | Proportion of Participants Who Developed Hypertensive Diseases in Pregnancy | 3 Participants |
p-value: 0.8Chi-squared
Secondary
Proportion of Participants With Consistent GDM Mechanism Before and and After Treatment Initiation
Time frame: 2 weeks after treatment initiation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Proportion of Participants With Consistent GDM Mechanism Before and and After Treatment Initiation | 22 Participants |
| Individualized Treatment | Proportion of Participants With Consistent GDM Mechanism Before and and After Treatment Initiation | 21 Participants |
p-value: 0.9Fisher Exact
Secondary
Proportion of Women Who Remain on Same Treatment During Study
Time frame: Through study completion, an average of 16 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Proportion of Women Who Remain on Same Treatment During Study | 25 Participants |
| Individualized Treatment | Proportion of Women Who Remain on Same Treatment During Study | 26 Participants |
p-value: 0.9Fisher Exact