Treatment of Mild Gestational Diabetes With Glyburide Versus Placebo

• Sponsor: University of Texas Southwestern Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00744965
• Collaborator: (none)
• Enrollment: 395
• Location: 1
• Arms: 2
• Actual Duration (Months): 87.5
• Patients Per Site Per Month: 4.5

Study Details

Study Description

Brief Summary

This is a randomized prospective trial which addresses the question of whether use of an oral hypoglycemic agent as an adjunct to diet therapy in women with mild gestational diabetes will result in achieving euglycemia in a shorter period of time and, in turn, result in less frequent maternal and neonatal morbidities. This study is designed to test the hypothesis that in women with mild GDM, use of Glyburide in addition to diet and nutritional counseling lowers mean infant birth weight by 200 grams as compared with diet and nutritional counseling alone.

Condition or Disease	Intervention/Treatment	Phase
Mild Gestational Diabetes	Drug: Glyburide; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 395 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized Controlled Clinical Trial of Treatment of Mild Gestational Diabetes With Glyburide Versus Placebo
• Actual Study Start Date: Sep 16, 2008
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Glyburide Women with mild gestational diabetes will be started ADA diet and a low dose of Glyburide and their medication dosage will be titrated as necessary during the pregnancy to achieve glucose control.	Drug: Glyburide; Starting dosage is 2.5 mg once daily. This dose will be titrated as necessary during the pregnancy to achieve glycemic control.
Placebo Comparator: Placebo Women with mild gestational diabetes will be started ADA diet and placebo.	Drug: Placebo; Sham dose adjustments of the placebo will be made.

Outcome Measures

Primary Outcome Measures

1. Mean Fetal Weight at Birth [Immediately after delivery of fetus]

Secondary Outcome Measures

1. Number of Participants With Large for Gestational Age Infants [After delivery]

   Birth weight exceeding the 90th percentile for the gestational age at delivery.

2. Macrosomia [After delivery]

   birth weight 4,000 g or greater

3. Neonatal Intensive Care Unit Admissions [Until hospital discharge]

4. Rate of Cesarean Delivery [After delivery]

5. Diagnosis of Pregnancy-induced Hypertension [until hospital discharge]

6. Shoulder Dystocia [at delivery]

7. Need for Insulin Treatment [after delivery]

8. 3rd or 4th Degree Perineal Laceration [at delivery]

9. Chorioamnionitis [intrapartum]

   Maternal fever >=38.0°C

10. Need for Insulin Therapy [throughout pregnancy and delivery]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 45 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• A glucose value of ≥140 mg/dl on a 50-gram oral glucose loading test by plasma at gestational age between 24 weeks 0 days and 27 weeks 6 days based on clinical information

• An Abnormal 3-hour oral glucose tolerance test with a fasting glucose of ≤105 mg/dl

• Gestational age of less than or equal to 28 weeks and 0 days at the time of consent/randomization

• Singleton gestation

Exclusion Criteria:

• Established pregestational diabetes

• Abnormal gestational diabetes testing (≥140) prior to 24 weeks 0 days of gestation. Women who have a negative glucose loading test (<140mg/dl) before 24 weeks may still be considered for this study if they present again for glucose tolerance testing between 24 and 27 weeks.

• Multiple gestations

• Known major fetal anomaly or fetal demise

• Any renal disease with serum creatinine of >1.0

• Known liver disease such as hepatitis

• Maternal or fetal conditions likely to require imminent or very preterm delivery such as preeclampsia, preterm premature rupture of the membranes, preterm labor, and intrauterine fetal growth restriction

• Known hypersensitivity or allergic reaction to Glyburide

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Parkland Memorial Hospital	Dallas	Texas	United States	75235

Sponsors and Collaborators

• University of Texas Southwestern Medical Center

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kenneth Leveno, Professor, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT00744965
• Other Study ID Numbers: 032011-086; 042008-058; NCT00942552
• First Posted: Sep 1, 2008
• Last Update Posted: Mar 12, 2020
• Last Verified: Mar 1, 2020

• Additional relevant MeSH terms: Diabetes, Gestational; Diabetes Mellitus; Glyburide

Study Results

Participant Flow

Arm/Group Title	Placebo	Glyburide
Arm/Group Description	Women with mild gestational diabetes will be started ADA diet and placebo. Placebo: Sham dose adjustments of the placebo will be made.	Women with mild gestational diabetes will be started ADA diet and a low dose of Glyburide and their medication dosage will be titrated as necessary during the pregnancy to achieve glucose control. Glyburide: Starting dosage is 2.5 mg once daily. This dose will be titrated as necessary during the pregnancy to achieve glycemic control.
Period Title: Overall Study
STARTED	197	198
COMPLETED	186	189
NOT COMPLETED	11	9

Baseline Characteristics

Arm/Group Title	Glyburide	Placebo	Total
Arm/Group Description	Women with mild gestational diabetes will be started ADA diet and a low dose of Glyburide and their medication dosage will be titrated as necessary during the pregnancy to achieve glucose control. Glyburide: Starting dosage is 2.5 mg once daily. This dose will be titrated as necessary during the pregnancy to achieve glycemic control.	Women with mild gestational diabetes will be started ADA diet and placebo. Placebo: Sham dose adjustments of the placebo will be made.	Total of all reporting groups
Overall Participants	189	186	375
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	189 100%	186 100%	375 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.3 (6)	31.2 (6)	31.2 (6)
Sex: Female, Male (Count of Participants)
Female	189 100%	186 100%	375 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	189 100%	186 100%	375 100%

Outcome Measures

1. Primary Outcome

Title	Mean Fetal Weight at Birth
Time Frame	Immediately after delivery of fetus

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Glyburide
Arm/Group Description	Women with mild gestational diabetes will be started ADA diet and placebo. Placebo: Sham dose adjustments of the placebo will be made.	Women with mild gestational diabetes will be started ADA diet and a low dose of Glyburide and their medication dosage will be titrated as necessary during the pregnancy to achieve glucose control. Glyburide: Starting dosage is 2.5 mg once daily. This dose will be titrated as necessary during the pregnancy to achieve glycemic control.
Measure Participants	186	189
Mean (Standard Deviation) [grams]	3355 (521)	3322 (481)

2. Secondary Outcome

Title	Number of Participants With Large for Gestational Age Infants
Description	Birth weight exceeding the 90th percentile for the gestational age at delivery.
Time Frame	After delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Glyburide
Arm/Group Description	Women with mild gestational diabetes will be started ADA diet and placebo. Placebo: Sham dose adjustments of the placebo will be made.	Women with mild gestational diabetes will be started ADA diet and a low dose of Glyburide and their medication dosage will be titrated as necessary during the pregnancy to achieve glucose control. Glyburide: Starting dosage is 2.5 mg once daily. This dose will be titrated as necessary during the pregnancy to achieve glycemic control.
Measure Participants	186	189
Count of Participants [Participants]	22 11.6%	20 10.8%

3. Secondary Outcome

Title	Macrosomia
Description	birth weight 4,000 g or greater
Time Frame	After delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Glyburide
Arm/Group Description	Women with mild gestational diabetes will be started ADA diet and placebo. Placebo: Sham dose adjustments of the placebo will be made.	Women with mild gestational diabetes will be started ADA diet and a low dose of Glyburide and their medication dosage will be titrated as necessary during the pregnancy to achieve glucose control. Glyburide: Starting dosage is 2.5 mg once daily. This dose will be titrated as necessary during the pregnancy to achieve glycemic control.
Measure Participants	186	189
Count of Participants [Participants]	18 9.5%	13 7%

4. Secondary Outcome

Title	Neonatal Intensive Care Unit Admissions
Time Frame	Until hospital discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Glyburide
Arm/Group Description	Women with mild gestational diabetes will be started ADA diet and placebo. Placebo: Sham dose adjustments of the placebo will be made.	Women with mild gestational diabetes will be started ADA diet and a low dose of Glyburide and their medication dosage will be titrated as necessary during the pregnancy to achieve glucose control. Glyburide: Starting dosage is 2.5 mg once daily. This dose will be titrated as necessary during the pregnancy to achieve glycemic control.
Measure Participants	186	189
Count of Participants [Participants]	11 5.8%	13 7%

5. Secondary Outcome

Title	Rate of Cesarean Delivery
Time Frame	After delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Glyburide
Arm/Group Description	Women with mild gestational diabetes will be started ADA diet and placebo. Placebo: Sham dose adjustments of the placebo will be made.	Women with mild gestational diabetes will be started ADA diet and a low dose of Glyburide and their medication dosage will be titrated as necessary during the pregnancy to achieve glucose control. Glyburide: Starting dosage is 2.5 mg once daily. This dose will be titrated as necessary during the pregnancy to achieve glycemic control.
Measure Participants	186	189
Count of Participants [Participants]	67 35.4%	70 37.6%

6. Secondary Outcome

Title	Diagnosis of Pregnancy-induced Hypertension
Time Frame	until hospital discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Glyburide
Arm/Group Description	Women with mild gestational diabetes will be started ADA diet and placebo. Placebo: Sham dose adjustments of the placebo will be made.	Women with mild gestational diabetes will be started ADA diet and a low dose of Glyburide and their medication dosage will be titrated as necessary during the pregnancy to achieve glucose control. Glyburide: Starting dosage is 2.5 mg once daily. This dose will be titrated as necessary during the pregnancy to achieve glycemic control.
Measure Participants	186	189
Count of Participants [Participants]	12 6.3%	15 8.1%

7. Secondary Outcome

Title	Shoulder Dystocia
Time Frame	at delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Glyburide
Arm/Group Description	Women with mild gestational diabetes will be started ADA diet and placebo. Placebo: Sham dose adjustments of the placebo will be made.	Women with mild gestational diabetes will be started ADA diet and a low dose of Glyburide and their medication dosage will be titrated as necessary during the pregnancy to achieve glucose control. Glyburide: Starting dosage is 2.5 mg once daily. This dose will be titrated as necessary during the pregnancy to achieve glycemic control.
Measure Participants	186	189
Count of Participants [Participants]	1 0.5%	0 0%

8. Secondary Outcome

Title	Need for Insulin Treatment
Time Frame	after delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Glyburide
Arm/Group Description	Women with mild gestational diabetes will be started ADA diet and placebo. Placebo: Sham dose adjustments of the placebo will be made.	Women with mild gestational diabetes will be started ADA diet and a low dose of Glyburide and their medication dosage will be titrated as necessary during the pregnancy to achieve glucose control. Glyburide: Starting dosage is 2.5 mg once daily. This dose will be titrated as necessary during the pregnancy to achieve glycemic control.
Measure Participants	186	189
Count of Participants [Participants]	4 2.1%	4 2.2%

9. Secondary Outcome

Title	3rd or 4th Degree Perineal Laceration
Time Frame	at delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Glyburide
Arm/Group Description	Women with mild gestational diabetes will be started ADA diet and placebo. Placebo: Sham dose adjustments of the placebo will be made.	Women with mild gestational diabetes will be started ADA diet and a low dose of Glyburide and their medication dosage will be titrated as necessary during the pregnancy to achieve glucose control. Glyburide: Starting dosage is 2.5 mg once daily. This dose will be titrated as necessary during the pregnancy to achieve glycemic control.
Measure Participants	186	189
Count of Participants [Participants]	5 2.6%	1 0.5%

10. Secondary Outcome

Title	Chorioamnionitis
Description	Maternal fever >=38.0°C
Time Frame	intrapartum

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Glyburide
Arm/Group Description	Women with mild gestational diabetes will be started ADA diet and placebo. Placebo: Sham dose adjustments of the placebo will be made.	Women with mild gestational diabetes will be started ADA diet and a low dose of Glyburide and their medication dosage will be titrated as necessary during the pregnancy to achieve glucose control. Glyburide: Starting dosage is 2.5 mg once daily. This dose will be titrated as necessary during the pregnancy to achieve glycemic control.
Measure Participants	186	189
Count of Participants [Participants]	12 6.3%	15 8.1%

11. Secondary Outcome

Title	Need for Insulin Therapy
Time Frame	throughout pregnancy and delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Glyburide
Arm/Group Description	Women with mild gestational diabetes will be started ADA diet and placebo. Placebo: Sham dose adjustments of the placebo will be made.	Women with mild gestational diabetes will be started ADA diet and a low dose of Glyburide and their medication dosage will be titrated as necessary during the pregnancy to achieve glucose control. Glyburide: Starting dosage is 2.5 mg once daily. This dose will be titrated as necessary during the pregnancy to achieve glycemic control.
Measure Participants	186	189
Count of Participants [Participants]	4 2.1%	4 2.2%

Adverse Events

Time Frame	approximately 3-4 months (throughout the duration of study participation)
Arm/Group Title	Placebo		Glyburide
Arm/Group Description	Women with mild gestational diabetes will be started ADA diet and placebo. Placebo: Sham dose adjustments of the placebo will be made.		Women with mild gestational diabetes will be started ADA diet and a low dose of Glyburide and their medication dosage will be titrated as necessary during the pregnancy to achieve glucose control. Glyburide: Starting dosage is 2.5 mg once daily. This dose will be titrated as necessary during the pregnancy to achieve glycemic control.
All Cause Mortality
	Placebo		Glyburide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/186 (0%)		0/189 (0%)
Serious Adverse Events
	Placebo		Glyburide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/186 (0%)		1/189 (0.5%)
Endocrine disorders
facial swelling	0/186 (0%)	0	1/189 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Glyburide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/186 (0%)		0/189 (0%)

Limitations/Caveats

Sample size of 395 limits our ability to analyze the effect of Glyburide on uncommon pregnancy outcomes. The study was underpowered for outcomes other than birth weight difference.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.