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Glyburide and Metformin for Gestational Diabetes Mellitus (GDM) (GDM)

Primary Purpose

Gestational Diabetes Mellitus

Status
Unknown status
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Glyburide
Metformin
Glyburide-Metformin combination
Sponsored by
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gestational Diabetes Mellitus focused on measuring Pregnancy, Glyburide, Metformin, Pharmacokinetics, Pharmacodynamics

Eligibility Criteria

18 Years - 45 Years (Adult)FemaleAccepts Healthy Volunteers

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.

Sites / Locations

  • Indiana University School of Medicine
  • University of Pittsburgh
  • University of Texas Medical Branch
  • University of Washington

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

No Intervention

No Intervention

Arm Label

GDM Subjects

Non-pregnant Type 2 Diabetes Milletus Subjects

Healthy Pregnant Women

Arm Description

Women with GDM requiring treatment

Non-pregnant women with Type 2 diabetes mellitus who plan to use metformin treatment

Healthy pregnant women with normal 1-hour glucose tolerance test

Outcomes

Primary Outcome Measures

Study drug dosage in pregnancy
(1) Determination of metformin dosage in pregnancy needed to produce comparable concentrations to the approved dosage range in non-pregnant women. (2)To compare metformin apparent oral clearance in pregnant and non-pregnant women. (3)To evaluate the effect of GLY monotherapy, MET monotherapy, and GLY-MET combination on insulin sensitivity, beta-cell responsivity index and disposition index (response vectors) describing the mechanism and magnitude of effect.

Secondary Outcome Measures

Determine GLY and MET PK parameters
Determining GLY & MET PK parameters, including AUC, max concentration, time to max & min concentrations, oral clearance, half-life, oral volume of distribution, umbilical cord plasma concentrations; correlation between CYP2C9, CYP3A5, BCRP, OATP2B1 genotypes & GLY PK/PD; GLY & MET PD parameters, including derived parameters from PK/PD modeling for pregnant & nonpregnant subjects; duration of initiation of treatment to glycemic control; effects of GDM & glycemic control on maternal & umbilical cord EPC cells & sFLT concentrations; GLY & MET half-life in neonates; efficacy & safety data.

Full Information

First Posted
March 22, 2011
Last Updated
February 9, 2015
Sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators
University of Washington, University of Pittsburgh, University of Texas, Indiana University School of Medicine, RTI International
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1. Study Identification

Unique Protocol Identification Number
NCT01329016
Brief Title
Glyburide and Metformin for Gestational Diabetes Mellitus (GDM)
Acronym
GDM
Official Title
Glyburide and Metformin for Gestational Diabetes Mellitus
Study Type
Interventional

2. Study Status

Record Verification Date
February 2015
Overall Recruitment Status
Unknown status
Study Start Date
July 2011 (undefined)
Primary Completion Date
May 2015 (Anticipated)
Study Completion Date
June 2015 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators
University of Washington, University of Pittsburgh, University of Texas, Indiana University School of Medicine, RTI International

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gestational Diabetes Mellitus
Keywords
Pregnancy, Glyburide, Metformin, Pharmacokinetics, Pharmacodynamics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
360 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
GDM Subjects
Arm Type
Active Comparator
Arm Description
Women with GDM requiring treatment
Arm Title
Non-pregnant Type 2 Diabetes Milletus Subjects
Arm Type
No Intervention
Arm Description
Non-pregnant women with Type 2 diabetes mellitus who plan to use metformin treatment
Arm Title
Healthy Pregnant Women
Arm Type
No Intervention
Arm Description
Healthy pregnant women with normal 1-hour glucose tolerance test
Intervention Type
Drug
Intervention Name(s)
Glyburide
Intervention Description
Women with GDM who require treatment will be given glyburide 2.5 mg. Medication will be given at least twice daily and equal doses will be given for each dosing time for the 3 days prior to the pharmacokinetic study day.
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
Women with GDM requiring treatment will be given metformin 500 mg. Medication will be administered at least twice daily and equal doses will be given for each dosing time for the 3 days prior to the pharmacokinetic study day.
Intervention Type
Drug
Intervention Name(s)
Glyburide-Metformin combination
Intervention Description
Women with GDM requiring treatment will be given glyburide 2.5 mg with metformin 500 mg. Medications will be administered at least twice daily and equal doses will be given for each dosing time 3 days prior to the pharmacokinetic study day.
Primary Outcome Measure Information:
Title
Study drug dosage in pregnancy
Description
(1) Determination of metformin dosage in pregnancy needed to produce comparable concentrations to the approved dosage range in non-pregnant women. (2)To compare metformin apparent oral clearance in pregnant and non-pregnant women. (3)To evaluate the effect of GLY monotherapy, MET monotherapy, and GLY-MET combination on insulin sensitivity, beta-cell responsivity index and disposition index (response vectors) describing the mechanism and magnitude of effect.
Time Frame
Completion of data collection (4-5mnths on average in GDM and healthy pregnant women and max of 6 months in newly diagnosed T2DMs)
Secondary Outcome Measure Information:
Title
Determine GLY and MET PK parameters
Description
Determining GLY & MET PK parameters, including AUC, max concentration, time to max & min concentrations, oral clearance, half-life, oral volume of distribution, umbilical cord plasma concentrations; correlation between CYP2C9, CYP3A5, BCRP, OATP2B1 genotypes & GLY PK/PD; GLY & MET PD parameters, including derived parameters from PK/PD modeling for pregnant & nonpregnant subjects; duration of initiation of treatment to glycemic control; effects of GDM & glycemic control on maternal & umbilical cord EPC cells & sFLT concentrations; GLY & MET half-life in neonates; efficacy & safety data.
Time Frame
Conclusion of data collection (up to 6 months)

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Gestational Diabetes Subject Selection Pregnant women (singleton pregnancy) Gestational diabetes mellitus Able to give written informed consent Drug treatment is required for GDM 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 Willing to avoid ethanol 18-45 years of age Type 2 Diabetes Mellitus Subject Selection Able to give written informed consent New diagnosis of type 2 diabetes mellitus Plan to receive metformin for treatment of type 2 diabetes mellitus 18-45 years of age Female Negative pregnancy test Hemoglobin A1C > 7% Healthy Pregnant Women Able to give written informed consent Pregnant women (singleton) Normal 1-hour glucose tolerance test 20-32 weeks gestation 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 Women taking medications expected to interact with glyburide, metformin or alter blood glucose concentrations Serum creatinine > 1.2 mg/dL Hematocrit < 28% Allergy to glyburide, metformin or sulfa Significant hepatic disease Congestive heart failure or history of MI Moderate to severe pulmonary disease Adrenal or pituitary insufficiency Healthy Pregnant Women Receiving any hypoglycemic agents Receiving corticosteroids Known kidney, liver, heart, pulmonary, adrenal or pituitary disease Hematocrit < 28% Neonates 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. Infants < 1.5 kg will be included for clinical outcomes data collection, but will be excluded from blood sample collection.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mary F. Hebert, PharmD, FCCP
Organizational Affiliation
University of Washington
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Steve Caritis, MD
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Gary DV Hankins, MD
Organizational Affiliation
University of Texas
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David Flockhart, MD, PhD
Organizational Affiliation
Indiana University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Indiana University School of Medicine
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
University of Texas Medical Branch
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States

12. IPD Sharing Statement

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Glyburide and Metformin for Gestational Diabetes Mellitus (GDM)

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