Clinical trial NCT01329016: Glyburide and Metformin for Gestational Diabetes Mellitus (GDM)
Official title: Glyburide and Metformin for Gestational Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Gestational Diabetes Mellitus
Keywords: Pregnancy
Glyburide
Metformin
Pharmacokinetics
Pharmacodynamics
Lead sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sponsor class: NIH
Collaborators: name: University of Washington
name: University of Pittsburgh
name: University of Texas
name: Indiana University School of Medicine
name: RTI International
First posted: 2011-04-05
Enrollment: 360
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a pharmacokinetic and pharmacodynamic study evaluating glyburide, metformin, and combination treatment for gestational diabetes mellitus.

Detailed description: Gestational diabetes mellitus (GDM) is a common complication of pregnancy. Multiple treatment regimens are currently used for the management of GDM. Following failure of diet therapy, insulin, glyburide and metformin are all used in the treatment of GDM with the oral medications providing comparable outcomes with insulin but easier route of administration and schedule. The proposed work will evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of glyburide and metformin alone and in combination in order to lay the foundation in establishing dosage and response information that could be utilized in designing a phase III randomized trial that will ultimately evaluate GDM treatment optimization.

Eligibility criteria: Inclusion Criteria:

Gestational Diabetes Subject Selection

1. Pregnant women (singleton pregnancy)
2. Gestational diabetes mellitus
3. Able to give written informed consent
4. Drug treatment is required for GDM
5. Gestational age 20-32 weeks

   * Gestational diabetes diagnosis must occur after 20 weeks and prior to 32 weeks gestation
   * Randomization and treatment initiation must occur no later than 32 weeks gestation
6. Willing to avoid ethanol
7. 18-45 years of age

Type 2 Diabetes Mellitus Subject Selection

1. Able to give written informed consent
2. New diagnosis of type 2 diabetes mellitus
3. Plan to receive metformin for treatment of type 2 diabetes mellitus
4. 18-45 years of age
5. Female
6. Negative pregnancy test
7. Hemoglobin A1C \> 7%

Healthy Pregnant Women

1. Able to give written informed consent
2. Pregnant women (singleton)
3. Normal 1-hour glucose tolerance test
4. 20-32 weeks gestation
5. 18-45 years of age

Neonates: All the infants of the pregnant women participating in this study will be included

Exclusion Criteria:

Women with GDM and T2DM

1. Women taking medications expected to interact with glyburide, metformin or alter blood glucose concentrations
2. Serum creatinine \> 1.2 mg/dL
3. Hematocrit \< 28%
4. Allergy to glyburide, metformin or sulfa
5. Significant hepatic disease
6. Congestive heart failure or history of MI
7. Moderate to severe pulmonary disease
8. Adrenal or pituitary insufficiency

Healthy Pregnant Women

1. Receiving any hypoglycemic agents
2. Receiving corticosteroids
3. Known kidney, liver, heart, pulmonary, adrenal or pituitary disease
4. Hematocrit \< 28%

Neonates

1. Infants that are not viable or too ill for blood sample collection will be included for clinical outcomes data collection, but will be excluded from other research activities.
2. Infants \< 1.5 kg will be included for clinical outcomes data collection, but will be excluded from blood sample collection.

Primary outcomes:
measure: Study drug dosage in pregnancy
timeFrame: Completion of data collection (4-5mnths on average in GDM and healthy pregnant women and max of 6 months in newly diagnosed T2DMs)
Secondary outcomes:
measure: Determine GLY and MET PK parameters
timeFrame: Conclusion of data collection (up to 6 months)
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Washington
name: Mary F. Hebert, PharmD, FCCP
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Steve Caritis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas
name: Gary DV Hankins, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University School of Medicine
name: David Flockhart, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: