Glycemic Control After Antenatal Corticosteroids in Women With Pregestational and Gestational Diabetes

October 1, 2023 updated by: Ashley N. Battarbee, University of Alabama at Birmingham

Glycemic Control After Antenatal Corticosteroids in Women With Pregestational and Gestational Diabetes (Close the GAP)

There is a fundamental gap in understanding the maternal and neonatal effects of antenatal corticosteroid (ACS) administration in women with threatened preterm birth (PTB) who have diabetes. Since the initial discovery of ACS for neonatal benefit in 1972, more than 40 randomized controlled trials have been performed evaluating its efficacy. However, none of these trials have included women with T2DM, and there is limited data among women with gestational diabetes. While ACS have been shown to reduce neonatal morbidity associated with PTB in non-diabetic women, the side effects of ACS (maternal hyperglycemia and fetal hyperinsulinemia) may mitigate the neonatal benefit of ACS in women with diabetes. Before neonatal benefit of ACS can be evaluated in this population, the first step is to optimize maternal glycemic control after ACS. Previous studies evaluating maternal hyperglycemia after ACS have been limited by small sample size, retrospective study design, or insufficient glucose data. Use of continuous glucose monitoring (CGM) in a randomized clinical trial provides a unique opportunity to overcome these challenges. Our long-term goal is to improve maternal and child health among women with diabetes as an independently funded clinical researcher. The research objectives of this proposal are to test the efficacy of three treatment strategies at achieving maternal glycemic control after ACS and evaluate the association between maternal glycemic control and neonatal outcomes. Our central hypothesis is that treatment with a continuous insulin infusion will improve maternal glycemic control, which is key to improving neonatal outcomes, but at the cost of less patient satisfaction and more health resource utilization. This hypothesis will be tested by pursuing the following specific aims: 1) Test the efficacy of three treatment strategies (addition of sliding scale insulin, up-titration of home insulin, and continuous insulin infusion) at achieving maternal glycemic control after ACS and 2) Quantify the association between maternal glycemic control after ACS and neonatal morbidity. Completion of these aims will determine the optimal strategy to achieve maternal glycemic control after ACS and inform a larger, multicenter trial to improve neonatal outcomes among women with diabetes and threatened PTB.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Eligible, consenting women with medication-treated gestational or pregestational type 2 diabetes receiving ACS at 23 0/7 - 36 5/7 weeks' gestation for threatened PTB will be enrolled and randomized in a 1:1:1 ratio to receive 1) addition of sliding scale insulin to their home insulin regimen, 2) up-titration of their home insulin regimen, or 3) discontinuation of their home insulin regimen and initiation of a continuous insulin infusion. The randomization sequence will be created by the study statistician in a permuted block design, and assignments will be centrally allocated using the Research Electronic Data Capture (REDCap) application. Study investigators will be masked to the randomization sequence and varying block sizes.

Regardless of treatment group, all women will receive Dexcom G6 Professional CGM for 10 days. The device will be applied by research staff or if desired, by the patient herself, under direct supervision by research staff. The CGM sensor will be applied to the patient's abdomen away from skin folds, where there is hair, near the waistband or areas of scarring, tatoos, irritation or open wounds. An additional waterproof adhesive will be applied to help prevent the sensor from being dislodged and finally the transmitter will be attached. The patient will be provided a handout with instructions for care. The Professional CGM device will ensure both patients and providers are masked to CGM data, which will be used for research purposes only as CGM is not readily available to guide insulin titration in most clinical settings. Capillary blood glucose testing, the method routinely used in clinical practice, will be used to guide insulin titration for each treatment group. Women assigned to the sliding scale insulin group will continue their home insulin regimen and receive supplemental insulin as needed for post-prandial hyperglycemia based on capillary blood glucose testing 4 times daily (fasting and 1-hour post-prandial) for 5 days after ACS. Women assigned to the up-titration of home insulin group will have their home insulin dosages increased based on an algorithm with capillary blood glucose testing 4 times daily and additional sliding scale insulin as needed for post-prandial hyperglycemia. For example, if a woman's baseline insulin regimen includes a total of 70 units of daily insulin (NPH 30 units in the morning (qAM), NPH 10 units at bedtime (qPM), and Aspart 10 units with each meal), then on day 2 after ACS she will receive 50% more or 105 units total (NPH 45 units qAM, NPH 15 units qPM, and Aspart 15 units with each meal). Women assigned to the continuous insulin infusion group will have their home insulin discontinued and receive a continuous insulin infusion based on hourly capillary blood glucose testing for 5 days after ACS. Given the high acuity of insulin infusion management these women will be monitored on L&D, but women in the other two treatment groups may be managed on L&D or on the Antepartum unit at the discretion of the primary provider. Regardless of treatment group, all women will be allowed to eat as long as it is deemed safe by the primary provider. If women assigned to receive the sliding scale insulin group or the up-titration of home insulin group are made nil per os (NPO) at any time after enrollment, they will be placed on the continuous insulin infusion per protocol with hourly capillary blood glucose testing. Once a diet is resumed, they will be switched back to the insulin algorithm.

Upon completion of the study intervention, all women will complete the Diabetes Treatment Satisfaction Questionnaire (DTSQ) to assess satisfaction with their insulin treatment strategy. The DTSQ is one of the most widely used treatment questionnaires as it is internationally validated and approved by the World Health Organization and International Diabetes Federation and available in over 100 different languages. The questionnaire is composed of 8 questions, each of which are scored on a scale ranging from 0 ("very dissatisfied or inconvenient") to 6 ("very satisfied or convenient"). The first section assesses treatment satisfaction and includes 6 questions that ask about 1) satisfaction with treatment, 2) flexibility, 3) convenience, 4) understanding of diabetes, 5) recommend treatment to others, and 6) willingness to continue. The second section consists of 2 questions that assess the burden of hyper- and hypoglycemia. Overall treatment satisfaction is measured by the sum of the scores on the first 6 questions, and a higher score indicates higher satisfaction (maximum score of 36). The DTSQ is particularly well-suited for use in this study because it is able assess treatment satisfaction regardless of the specific treatment method, and it is easy to answer without placing a large burden on patients.

Other than glycemic management during the 5 days after ACS, antenatal care (fetal testing, maternal laboratory evaluation, timing and mode of delivery) will be at the discretion of the primary obstetric provider. Umbilical cord blood will be collected at delivery and stored at the University of Alabama at Birmingham (UAB) for analysis at the conclusion of the trial. After birth, all neonates born to women with diabetes have a heelstick performed to measure capillary blood glucose as part of standard of care. Additional neonatal care after birth will be at the discretion of the primary neonatal provider.

Comprehensive baseline maternal data and maternal and neonatal outcomes will be abstracted from the UAB electronic medical record and Professional CGM devices. Additionally, measures of health resource utilization will be collected such as duration of time on labor and delivery, number of capillary blood glucose tests, treatments administered such as insulin, intravenous fluids, and dextrose for hypoglycemia.

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35223
        • Recruiting
        • University of Alabama at Birmingham
        • Contact:
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health and Science University
        • Contact:
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Recruiting
        • University of South Carolina Greenville / Prisma Health-Upstate
        • Contact:
    • Texas
      • Houston, Texas, United States, 77024
        • Recruiting
        • University of Texas Health Science Center at Houston
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 50 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Gestational or pregestational type 2 diabetes mellitus treated with daily insulin injection(s) or oral hypoglycemic agents such as metformin
  • Hospitalized for antenatal corticosteroid administration in anticipation of preterm birth
  • Gestational age 23 0/7 weeks - 36 5/7 weeks
  • Maternal age 18-50

Exclusion Criteria:

  • Planned delivery < 72 hours after 1st dose of antenatal corticosteroids
  • More than 16 hours after 1st dose of antenatal corticosteroids
  • Major fetal anomaly
  • Triplet or higher order multiple gestation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sliding Scale Insulin
Addition of supplemental sliding scale insulin to home insulin regimen for maximum of 5 days after antenatal corticosteroids
Drug: Sliding Scale Insulin
After antenatal corticosteroid administration, women will continue to receive long- and short-acting subcutaneous insulin injections as prescribed at home. In addition, they will receive supplemental short-acting insulin using a sliding scale based on postprandial glucose values. Capillary blood glucose values will be measured with fingersticks 4 times daily (fasting and 1-hour postprandial).
Other Names:
  • Aspart
  • Lispro
Device: Dexcom G6 Professional Continuous Glucose Monitor
Masked Dexcom G6 Pro devices will be worn for 10 days.
Other Names:
  • G6 Pro
Experimental: Up-Titration of Home Insulin
Increase in home insulin regimen based on standardized algorithm for maximum of 5 days after antenatal corticosteroids
Device: Dexcom G6 Professional Continuous Glucose Monitor
Masked Dexcom G6 Pro devices will be worn for 10 days.
Other Names:
  • G6 Pro
Drug: Up-Titration of Home Insulin
After antenatal corticosteroid administration, women will receive long- and short-acting subcutaneous insulin injections at increased dosages compared to that prescribed at home. Insulin will be increased by 30% on the day that they receive their 1st dose of antenatal corticosteroids (day 1), 50% on day 2, 50% on day 3, 30% on day 4, and 15% increase on day 5. On day 6 they will return to their home insulin regimen. Capillary blood glucose values will be measured with fingersticks 4 times daily (fasting and 1-hour postprandial).
Other Names:
  • Aspart
  • Lispro
  • Glargine
  • NPH
  • Regular insulin
Experimental: Continuous Insulin Infusion
Discontinuation of home insulin regimen and receipt of continuous insulin infusion for maximum of 5 days after antenatal corticosteroids
Device: Dexcom G6 Professional Continuous Glucose Monitor
Masked Dexcom G6 Pro devices will be worn for 10 days.
Other Names:
  • G6 Pro
Drug: Continuous Insulin Infusion
After antenatal corticosteroid administration, women will discontinue their home insulin regimen and be placed on a continuous insulin infusion with insulin boluses and titration of infusion rate per institutional L&D protocol. Capillary blood glucose values will be measured with fingersticks every hour.
Other Names:
  • Regular insulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time In Range
Time Frame: During study intervention assessed for maximum of 5 days after ACS
Percent time glucose in range (65-140mg/dL) on CGM
During study intervention assessed for maximum of 5 days after ACS

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time Above Range
Time Frame: During study intervention assessed for maximum of 5 days after ACS
Percent time glucose above range (>140mg/dL) on CGM
During study intervention assessed for maximum of 5 days after ACS
Time Below Range
Time Frame: During study intervention assessed for maximum of 5 days after ACS
Percent time glucose below range (<65mg/dL) on CGM
During study intervention assessed for maximum of 5 days after ACS
Additional insulin requirement
Time Frame: During study intervention assessed for maximum of 5 days after ACS
Percent increase in daily insulin requirements compared to home regimen
During study intervention assessed for maximum of 5 days after ACS
Glucose variability
Time Frame: During study intervention assessed for maximum of 5 days after ACS
Coefficient of variation (glucose standard deviation / mean glucose) on CGM
During study intervention assessed for maximum of 5 days after ACS
Patient satisfaction
Time Frame: Upon completion of study intervention, on average 5 days after enrollment
Score on modified Diabetes Treatment Satisfaction Questionnaire (questions 1, 4, 5, 6, 7, 8) with score range from 0-36 with 0 being not satisfied and 36 being very satisfied
Upon completion of study intervention, on average 5 days after enrollment
Neonatal composite respiratory morbidity
Time Frame: Birth to hospital discharge, assessed up to 28 days
Composite including need for continuous positive airway pressure or high-flow nasal cannula of >=0.30 for >=12 continuous hours, respiratory distress syndrome, or mechanical ventilation
Birth to hospital discharge, assessed up to 28 days
Initial neonatal glucose
Time Frame: Birth to 2 hours of life
Initial capillary neonatal glucose in mg/dL measured by heelstick
Birth to 2 hours of life
Umbilical cord blood C-peptide
Time Frame: Delivery
C-peptide concentration (mcg/L) in the umbilical cord blood as measure of fetal insulin status
Delivery
Umbilical cord blood insulin
Time Frame: Delivery
Insulin concentration (mcg/L) in the umbilical cord blood as measure of fetal insulin status
Delivery
Umbilical cord blood cortisol
Time Frame: Delivery
Cortisol concentration (mcg/L) in the umbilical cord blood as measure of fetal HPA axis
Delivery
Umbilical cord blood surfactant protein A (SP-A)
Time Frame: Delivery
Fetal surfactant protein A
Delivery
Umbilical cord blood surfactant protein B (SP-B)
Time Frame: Delivery
Fetal surfactant protein B
Delivery
Umbilical cord blood surfactant protein C (SP-C)
Time Frame: Delivery
Fetal surfactant protein C
Delivery
Umbilical cord blood surfactant protein D (SP-D)
Time Frame: Delivery
Fetal surfactant protein D
Delivery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Alabama at Birmingham

Investigators

  • Principal Investigator: Ashley N Battarbee, MD, University of Alabama at Birmingham

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 10, 2022

Primary Completion (Estimated)

October 31, 2025

Study Completion (Estimated)

November 30, 2025

Study Registration Dates

First Submitted

August 18, 2020

First Submitted That Met QC Criteria

September 1, 2020

First Posted (Actual)

September 9, 2020

Study Record Updates

Last Update Posted (Actual)

October 4, 2023

Last Update Submitted That Met QC Criteria

October 1, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 300005848

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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