Trial record 17 of 48 for:    diabetes | NICHD [Lead] | NIH

Glyburide and Metformin for Gestational Diabetes Mellitus (GDM)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sponsor:
Collaborators:
University of Washington
University of Pittsburgh
University of Texas
Indiana University School of Medicine
RTI International
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT01329016
First received: March 22, 2011
Last updated: October 8, 2013
Last verified: July 2013
  Purpose

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


Condition Intervention Phase
Gestational Diabetes Mellitus
Drug: Glyburide
Drug: Metformin
Drug: Glyburide-Metformin combination
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Glyburide and Metformin for Gestational Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • Study drug dosage in pregnancy [ 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) ] [ Designated as safety issue: Yes ]
    (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 [ Time Frame: Conclusion of data collection (up to 6 months) ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 360
Study Start Date: July 2011
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: GDM Subjects
Women with GDM requiring treatment
Drug: Glyburide
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.
Drug: Metformin
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.
Drug: Glyburide-Metformin combination
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.
No Intervention: Non-pregnant Type 2 Diabetes Milletus Subjects
Non-pregnant women with Type 2 diabetes mellitus who plan to use metformin treatment
No Intervention: Healthy Pregnant Women
Healthy pregnant women with normal 1-hour glucose tolerance test

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

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01329016

Contacts
Contact: Mary Hebert, PharmD 206-616-5016 mhebert@u.washington.edu
Contact: Linda M Brown, MPH, DrPH 301-816-4626 lindabrown@rti.org

Locations
United States, Indiana
Indiana University School of Medicine Recruiting
Indianapolis, Indiana, United States, 46202
Contact: David Flockhart, MD, PhD    317-630-8795    dflockha@iupui.edu   
Contact: David Haas, MD, MS    317-630-7837    dahaas@iupui.edu   
Principal Investigator: David Flockhart, MD, MS         
United States, Pennsylvania
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Steve Caritis, MD    412-641-4874    scaritis@mail.magee.edu   
Contact: Raman Venkataramanan, PhD    412-648-8547    rv@pitt.edu   
Principal Investigator: Steve Caritis, MD         
United States, Texas
University of Texas Medical Branch Recruiting
Galveston, Texas, United States, 77555
Contact: Gary R. Hankins, MD    409-772-1957    ghankins@utmb.edu   
Contact: Shannon Clark, MD, MMS    409-772-1571    shclark@utmb.edu   
Principal Investigator: Gary R. Hankins, MD         
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98195
Contact: Mary F. Hebert, PharmD, FCCP    206-616-5016    mhebert@u.washington.edu   
Contact: Thomas Easterling, MD    206-543-1521    easter@u.washington.edu   
Principal Investigator: Mary F. Hebert, PharmD, FCCP         
Sponsors and Collaborators
University of Washington
University of Pittsburgh
University of Texas
Indiana University School of Medicine
RTI International
Investigators
Principal Investigator: Mary F. Hebert, PharmD, FCCP University of Washington
Principal Investigator: Steve Caritis, MD University of Pittsburgh
Principal Investigator: Gary DV Hankins, MD University of Texas
Principal Investigator: David Flockhart, MD, PhD Indiana University School of Medicine
  More Information

No publications provided

Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT01329016     History of Changes
Other Study ID Numbers: 820
Study First Received: March 22, 2011
Last Updated: October 8, 2013
Health Authority: United States: Institutional Review Board
United States: Federal Government

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
Pregnancy
Glyburide
Metformin
Pharmacokinetics
Pharmacodynamics

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes, Gestational
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pregnancy Complications
Glyburide
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014