Glycemic Control After Antenatal Corticosteroids in Women With Pregestational Diabetes

Sponsor
University of Alabama at Birmingham (Other)
Overall Status
Recruiting
CT.gov ID
NCT04542148
Collaborator
(none)
120
Enrollment
1
Location
3
Arms
43
Anticipated Duration (Months)
2.8
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 type 2 diabetes mellitus (T2DM). 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. 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 T2DM. 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 T2DM 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 T2DM and threatened PTB.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: Sliding Scale Insulin
  • Drug: Up-Titration of Home Insulin
  • Drug: Continuous Insulin Infusion
  • Device: Dexcom G6 Professional Continuous Glucose Monitor
Phase 2

Detailed Description

Eligible, consenting women with insulin-treated T2DM receiving ACS at 24 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 or hospital discharge. 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 T2DM 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 Design

Study Type:
Interventional
Anticipated Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Glycemic Control After Antenatal Corticosteroids in Women With Pregestational Diabetes (Close the GAP)
Anticipated Study Start Date :
Nov 30, 2021
Anticipated Primary Completion Date :
Dec 31, 2024
Anticipated Study Completion Date :
Jun 30, 2025

Arms and Interventions

ArmIntervention/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 or until hospital discharge.
    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

    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:
  • Glargine
  • NPH
  • Aspart
  • Lispro
  • Regular insulin
  • Device: Dexcom G6 Professional Continuous Glucose Monitor
    Masked Dexcom G6 Pro devices will be worn for 10 days or until hospital discharge.
    Other Names:
  • G6 Pro
  • Experimental: Continuous Insulin Infusion

    Discontinuation of home insulin regimen and receipt of continuous insulin infusion for maximum of 5 days after antenatal corticosteroids

    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
  • Device: Dexcom G6 Professional Continuous Glucose Monitor
    Masked Dexcom G6 Pro devices will be worn for 10 days or until hospital discharge.
    Other Names:
  • G6 Pro
  • Outcome Measures

    Primary Outcome Measures

    1. Time In Range [During study intervention assessed for maximum of 5 days after ACS]

      Percent time glucose in range (65-140mg/dL) on CGM

    Secondary Outcome Measures

    1. Time Above Range [During study intervention assessed for maximum of 5 days after ACS]

      Percent time glucose above range (>140mg/dL) on CGM

    2. Time Below Range [During study intervention assessed for maximum of 5 days after ACS]

      Percent time glucose below range (<65mg/dL) on CGM

    3. Additional insulin requirement [During study intervention assessed for maximum of 5 days after ACS]

      Percent increase in daily insulin requirements compared to home regimen

    4. Glucose variability [During study intervention assessed for maximum of 5 days after ACS]

      Coefficient of variation (glucose standard deviation / mean glucose) on CGM

    5. Patient satisfaction [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

    6. Neonatal composite respiratory morbidity [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

    7. Initial neonatal glucose [Birth to 2 hours of life]

      Initial capillary neonatal glucose in mg/dL measured by heelstick

    8. Umbilical cord blood C-peptide [Delivery]

      C-peptide concentration (mcg/L) in the umbilical cord blood as measure of fetal insulin status

    9. Umbilical cord blood insulin [Delivery]

      Insulin concentration (mcg/L) in the umbilical cord blood as measure of fetal insulin status

    10. Umbilical cord blood cortisol [Delivery]

      Cortisol concentration (mcg/L) in the umbilical cord blood as measure of fetal HPA axis

    11. Umbilical cord blood surfactant protein A (SP-A) [Delivery]

      Fetal surfactant protein A

    12. Umbilical cord blood surfactant protein B (SP-B) [Delivery]

      Fetal surfactant protein B

    13. Umbilical cord blood surfactant protein C (SP-C) [Delivery]

      Fetal surfactant protein C

    14. Umbilical cord blood surfactant protein D (SP-D) [Delivery]

      Fetal surfactant protein D

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 50 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Type 2 pregestational diabetes mellitus treated with multiple daily insulin injections

    • Hospitalized for antenatal corticosteroid administration in anticipation of preterm birth

    • Gestational age 24 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 6 hours after 1st dose of antenatal corticosteroids

    • Major fetal anomaly

    • Multiple gestation

    • Planned NPO status

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1University of Alabama at BirminghamBirminghamAlabamaUnited States35223

    Sponsors and Collaborators

    • University of Alabama at Birmingham

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Ashley N. Battarbee, Assistant Professor, University of Alabama at Birmingham
    ClinicalTrials.gov Identifier:
    NCT04542148
    Other Study ID Numbers:
    • 300005848
    First Posted:
    Sep 9, 2020
    Last Update Posted:
    Nov 17, 2021
    Last Verified:
    Nov 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Nov 17, 2021