Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04948112 |
| Other study ID # |
RP-21-012 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
October 1, 2021 |
| Est. completion date |
June 30, 2024 |
Study information
| Verified date |
December 2023 |
| Source |
Woman's |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The detection of and control of gestational diabetes carries benefits for both mother and
baby related to immediate pregnancy outcomes. The glycemic disorders in diabetes are not
solely limited to fasting and postprandial hyperglycemia, but can be extended to the glycemic
variability that includes both upward (postprandial glucose increments) and downward
(interprandial glucose decrements) changes. Glycemic variability, as a component of the
glycemic disorders, has more deleterious effects than sustained chronic hyperglycemia in the
development of diabetic complications. Glycemic variability is associated with increased
risks of adverse pregnancy outcomes in GDM. Hyperglycemic excursion has been shown to be the
strongest predictor of macrosomia, the most common complication of pregnancy with diabetes.
When compared with routine standard antenatal care, continuous glucose monitoring system
(CGMS) guided treatments should significantly improve glycemic control, lower infant birth
weight, and reduce risk of macrosomia in gestational women with diabetes. We will investigate
the following questions (1) Whether CGMS can detect greater glycemic variability in women
with an early GDM diagnosis; (2) Whether CGMS can subsequently moderate treatment strategies
of GDM especially patient behavior and glucose levels; (3) Whether CGMS can eventually
improve maternal (i.e., reduce gestational weight gain and lower glycemic levels during
pregnancy) and fetal outcomes (reduce LGA babies and C-section rate) compared with
traditional self-monitored blood glucose (SMBG) use.
Description:
Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with
onset during pregnancy. It is associated with increased feto-maternal morbidity as well as
with long-term complications in the mother and offspring . GDM is associated with significant
complications during pregnancy, including an increased need for Cesarean sections; higher
risks of ketonemia, preeclampsia, and urinary tract infection in both mothers and infants;
increased perinatal morbidity (e.g., macrosomia, neonatal hypoglycemia, and neonatal
jaundice); and possibly mortality. The risk of complications in women with GDM increases
proportionally with the worsening of glycemic tolerance. Comprehensive glucose monitoring and
therapy are indispensable to prevent these complications because even small increases in
maternal glucose are related to poorer clinical outcomes. Treatment of GDM during pregnancy,
centers on dietary modulation, promotion of healthy physical activity and pharmacologic
management, primarily with insulin as well as oral hypoglycemic agents (OHA), if glycemic
control cannot be achieved with lifestyle measures alone. The details of the therapeutic
approach, in particular regarding various dietary approaches and the potential use of OHAs
such as metformin and glyburide (glibenclamide) differ widely between and within countries.
Two landmark prospective randomized controlled trials have confirmed that detection of and
control of GDM carries benefits for both mother and baby in terms of immediate pregnancy
outcomes. Women in the intervention arm of the Australian (Crowther) study showed lower rates
of fetal macrosomia, reduced frequency of large-for-gestational age (LGA) babies and reduced
preeclampsia. In the US (Landon) study, women who received treatment for GDM demonstrated
lower gestational weight gain (GWG) and lower rates of pre-eclampsia. Reduced frequency of
LGA and macrosomia were noted in infants of treated mothers.
Glucose monitoring targets in pregnancy need to be tight, with low thresholds for commencing
pharmacotherapy or increasing the insulin dosage. The Hyperglycemia and Adverse Pregnancy
Outcomes (HAPO) study showed that a fasting glucose of 5.1 mmol/L in the oral glucose
tolerance test at 24-28 weeks of gestation was already associated with a 75% increased risk
of adverse outcomes . Self monitoring of blood glucose (SMBG) is a frequently used method to
monitor blood glucose during pregnancy. However, this method is not sufficient to detect all
glycemic fluctuations. Since the initiation of insulin/metformin/glyburide therapy and the
related dosage adjustments depend solely on the SMBG results, inaccurate results may lead to
a greater chance of hypo- or hyperglycemia and may even fail to detect hypoglycemic episodes.
Therefore, accurate SMBG results are crucial for management of hyperglycemia during
pregnancy. The capabilities of continuous glucose monitoring systems (CGMS) during pregnancy
have advanced with the technical aspects of glucose meters, and therefore considering these
aspects is important during pregnancy. Continuous glucose monitoring (CGM) provides unique
insights into daily glycemic control and permits a better understanding of how glucose
variability may influence acute and long-term complications of diabetes. Real-time CGM by
providing glucose measurements as often as every 5 minutes, low and high glucose alerts, and
glucose trend information, has the potential to better inform diabetes management decisions
compared with episodic self-monitoring with a SMBG. CGM offers a potential source of data
required to improve the detection and management of glucose levels in diabetic pregnancy. CGM
provides far more frequent glucose measurements than SMBG and far more information on
short-to-medium-term trends in glucose levels than either SMBG or even HbA1c. The slow
kinetics of glycosylated hemoglobin accumulation and physiological changes in erythrocyte
formation during pregnancy mean that A1C is only a limited predictor of acute blood glucose
changes providing an explanation for the poor pregnancy outcomes, even in women with
apparently "good" glycemic control . Recent attention has therefore focused on evaluating the
role of CGMS in pregnancy with studies providing normative data in diabetic and nondiabetic
pregnancies. CGMS is also capable of recording glucose levels throughout both day and night
without disrupting the normal activities of daily living (particularly periods of activity,
rest, and sleep). A real time-CGMS provides the patient with continuous information about the
alterations in the blood glucose levels throughout the day, which is immediately revealed to
the patient, and helps the patient to understand how food, exercise, and insulin affect blood
glucose. This visibility may empower the patient to modify his/her lifestyle and engage in
therapeutic management. CGMS data allows us to better understand where, when, and how we
might better invest our efforts to optimize glucose control in diabetic pregnancy to reduce
LGA and improve pregnancy outcomes.
CGMS use has been successful, safe, and accurate in detecting glucose levels in pregnancies
with diabetes. RT-CGMS studies in non-pregnant type 1 and type 2 diabetes patients reported
its efficacy in improving glycemic control. The effectiveness of CGMS in improving pregnancy
outcomes complicated by GDM is still understudied. In a study by Wei and colleagues, a total
of 106 women with GDM in gestational weeks 24-28 were randomly allocated to the antenatal
care plus CGMS group or the self-monitoring blood glucose (SMBG) group. The CGMS group was
subdivided into early and late subgroups. There were no significant differences in prenatal
or obstetric outcomes, e.g., caesarean delivery rate, Apgar score at 5 min, macrosomia or
neonatal hypoglycemia, between the CGMS and SMBG groups. The CGMS group had lower glycated
hemoglobin (HbA1C) levels than the SMBG group; however, the difference was not statistically
significant. The proportion of GDM women with excessive gestational weight gain was lower in
the CGMS group than in the SMBG group (33.3% vs. 56.4%, P = 0.039), and women who initiated
CGMS earlier gained less weight (P = 0.017). The mode of blood glucose monitoring (adjusted
OR 2.40; 95% CI 1.030-5.588; P = 0.042) and pre-pregnancy BMI (adjusted OR 0.578; 95% CI
0.419-0.798; P = 0.001) were independent factors for weight gain. The investigators concluded
that early CGMS for GDM mothers reduced gestational weight gain. Voormolen et al. randomized
109 women with GDM to CGMS vs. standard treatment (SMBG 4-8 times daily and HbA1c levels
every 4 weeks). Compared with SMBG users, CGMS users had a significantly lower incidence of
pre-eclampsia [Relative Risk (RR) 0.3; 95%Cl: 0.12-0.8]. In another study, Yu et al.
recruited 340 women with GDM and assigned 190 to routine care (SMBG 7 times daily) and the
other 150 to 72 h CGMS. Compared with SMBG, CGMS users tended to have lower incidence of
pre-eclampsia [5out of 150 (3.3%) vs. 19 out of 190 (10%), P = 0.019], primary cesarean
section [51 out of 150 (34.0%) vs. 88 out of 190 (46.3%), P =0.028], and premature delivery
[7 out of 150 (4.7%) vs. 22 out of 190 (11.6%), P = 0.024]. In addition, intermittent use of
retrospective CGM in pregnant women with pre-gestational diabetes or GDM was associated with
improvement in blood glucose and pregnancy outcomes.
This is a randomized controlled trial (RCT) which will assess CGMS vs. SMBG by allowing all
participants to use both methods but the SMBG group will be blinded to CGMS. A total of 121
women with gestational diabetes mellitus (GDM) diagnosed in gestational weeks 8-25 (6+0 to
25+6weeks) (by 8 weeks we can detect heartbeat and consider it a viable pregnancy) will be
recruited. We will investigate the following questions (1) Whether CGMS can detect greater
glycemic variability in women with an early GDM diagnosis; (2) Whether CGMS can subsequently
moderate treatment strategies of GDM especially patient behavior and glucose levels; (3)
Whether CGMS can eventually improve maternal (i.e., reduce gestational weight gain and lower
glycemic levels during pregnancy) and fetal outcomes (reduce LGA babies and C-section rate)
compared with traditional SMBG use.
