Sitagliptin + Metformin Compared to Metformin Monotherapy and Placebo in Women With a Recent GDM

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by BC Women's Hospital & Health Centre
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Karen Elkind-Hirsch, BC Women's Hospital & Health Centre
ClinicalTrials.gov Identifier:
NCT01856907
First received: May 14, 2013
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

Gestational diabetes mellitus (GDM) is defined as "any degree of glucose intolerance with onset or first recognition during pregnancy." GDM is one of the most frequent metabolic disorders occurring during pregnancy. Approximately 7% of all pregnancies in the United States are complicated by gestational diabetes resulting in more than 200,000 cases annually. There is epidemiologic evidence associating GDM with insulin resistance, glucose intolerance, and type 2 diabetes (DM2). Among all the risk factors of diabetes mellitus, the experience of gestational diabetes is the strongest one. Systematic reviews of older studies conclude that 35-60% women with gestational diabetes will develop type 2 diabetes at rates much greater than control groups who did not have glucose intolerance during pregnancy. Studies are needed for optimal postpartum and long-term health of women who have had GDM. Recent evidence suggests that incretin-based therapies may be useful for the treatment of DM2 because continuous administration of glucagon-like peptide 1 (GLP-1) produces substantial improvements in glucose control and ß-cell function in subjects with DM2. Inhibition of dipeptidyl peptidase-4 (DPP-4) increases the concentration of GLP-1 and may potentially delay disease progression in GDM considering the ß-cell function improvement in DM2 and ß-cell mass shown to increase in animal models. This study will examine if combination sitagliptin (a DPP-4 inhibitor)-plus metformin is more effective than metformin alone or placebo in improving metabolic parameters, specifically the impact on β-cell function, in prior GDM women with glucose abnormalities.


Condition Intervention Phase
Disorder of Glucose Regulation
Drug: Sitagliptin-Metformin
Drug: Metformin
Drug: Placebo pill
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Pilot Study Evaluating Combination Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Plus Metformin Compared to Metformin Monotherapy and Placebo on Metabolic Abnormalities in Women With a Recent History of GDM

Resource links provided by NLM:


Further study details as provided by BC Women's Hospital & Health Centre:

Primary Outcome Measures:
  • ß-cell compensatory function [ Time Frame: Change from baseline to 16 weeks ] [ Designated as safety issue: No ]
    • Improving ß-cell compensatory function by enhancing insulin release after an oral glucose load (following the OGTT) and thus improve or delay a decline in glucose tolerance estimated by the disposition index defined as the product of insulin action (Matsuda index) and insulin secretion (insulinogenic index) derived from the OGTT (SIOGTT x Δinsulin30-0 min to glucose30-0 min).

  • Surrogate measures of insulin sensitivity and secretion [ Time Frame: Change from baseline to 16 weeks ] [ Designated as safety issue: No ]
    •Improving markers of insulin sensitivity and secretion after an oral glucose load as measured by the Matsuda index and early insulin response adjusted for insulin sensitivity (insulinogenic index/homeostasis model assessment of insulin resistance [HOMA-IR])

  • Fasting and 2 hour glucose levels after glucose load [ Time Frame: Change from baseline to 16 weeks ] [ Designated as safety issue: No ]
    Correcting glucose control as evaluated by fasting and 2 hour glucose levels after an OGTT


Secondary Outcome Measures:
  • Cardiometabolic risk factors [ Time Frame: Change from baseline to 16 weeks ] [ Designated as safety issue: No ]
    We will further examine whether the addition of sitagliptin to metformin therapy is more beneficial than metformin alone or placebo in altering the development or progression of select cardiometabolic risk factors as measured by changes in lipids and blood pressure


Other Outcome Measures:
  • Liver enzymes [ Time Frame: Change from baseline to 16 weeks ] [ Designated as safety issue: Yes ]
    The safety criteria will include incidence and intensity of adverse events, withdrawals because of adverse events, physical exams, vital signs and laboratory parameters (liver enzymes)


Estimated Enrollment: 36
Study Start Date: September 2013
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitagliptin-Metformin
50 mg/1000 mg BID
Drug: Sitagliptin-Metformin
Experimental -DPP-4 inhibitor- oral medication
Other Name: Janumet
Placebo Comparator: Placebo pill
1 pill/BID for 16 weeks
Drug: Placebo pill
Will evaluate effect of lifestyle and diet only
Other Name: placebo control
Active Comparator: Metformin
1000 mg BID
Drug: Metformin
Biguanide- insulin sensitizer
Other Name: Glucophage

Detailed Description:

Gestational diabetes mellitus (GDM) is defined as "any degree of glucose intolerance with onset or first recognition during pregnancy." GDM is one of the most frequent metabolic disorders occurring during pregnancy. Approximately 7% of all pregnancies in the United States are complicated by gestational diabetes resulting in more than 200,000 cases annually. There is epidemiologic evidence associating GDM with insulin resistance, glucose intolerance, and type 2 diabetes (DM2). Among all the risk factors of diabetes mellitus, the experience of gestational diabetes is the strongest one.

Gestational diabetes is often the culmination of years of unrecognized and unmodified diabetes risk factors that lead to overt and occult clinical manifestations during pregnancy. Systematic reviews of older studies conclude that 35-60% women with gestational diabetes will develop type 2 diabetes at rates much greater than control groups who did not have glucose intolerance during pregnancy. The higher rates were in studies of particular ethnic groups in the U.S. Presently, in the literature, there are described new, more efficient methods of diabetes prevention in groups with a high risk of this disorder, which involve both, lifestyle modification and pharmacological therapies. Lifestyle intervention was found to reduce the incidence of type 2 diabetes by 58% and metformin by 31% as compared with placebo. Studies are needed for optimal postpartum and long-term health of women who have had GDM. Considerable recent evidence suggests that incretin-based therapies may be useful for the treatment of DM2 because continuous administration of glucagon-like peptide 1 (GLP-1) produces substantial improvements in glucose control and ß-cell function in subjects with type 2 diabetes. Inhibition of dipeptidyl peptidase-4 (DPP-4) increases the concentration of GLP-1 and may potentially delay disease progression in GDM considering the ß-cell function improvement in DM2 and ß-cell mass shown to increase in animal models. This study will examine if combination sitagliptin-plus metformin is more effective than metformin alone or placebo in improving metabolic parameters, specifically the impact on β-cell function, in at-risk women with a recent history of GDM.

  Eligibility

Ages Eligible for Study:   18 Years to 42 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Females 18 years to 42 years of age who experienced gestational diabetes mellitus (GDM) during recent (within 12 months) pregnancy with prediabetic hyperglycemia determined by an oral glucose tolerance test (OGTT) with 75 g glucose postpartum. Study subjects will be inclusive of prior GDM women with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both (IFG/IGT) postpartum.
  • Written consent for participation in the study

Exclusion Criteria:

  • Cholestasis during the past pregnancy
  • Any hepatic diseases in the past (viral hepatitis, toxic hepatic damage, jaundice of unknown etiology)
  • Serum aspartate transaminase (AST) and/or alanine aminotransferase (ALT) level exceeding more than twice normal lab values
  • Presence of hypersensitivity to sitagliptin or other DPP-4 inhibitor
  • Current use of metformin, thiazolidinediones, GLP-1 receptor agonists, DPP-4 inhibitors, or weight loss medications (prescription or over the counter [OTC])
  • Prior use of medication to treat diabetes except gestational diabetes
  • Use of drugs known to exacerbate glucose tolerance
  • History of diabetes or prior use of medications to treat diabetes except GDM
  • Creatinine clearance less than 60 ml/min
  • Pregnancy planned during the coming two years
  • Currently lactating
  • Patient not willing to use adequate contraception during study period (unless sterilized)
  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: NCT01856907

Contacts
Contact: Karen Elkind-Hirsch, Ph.D. 225-231-5278 karen.elkind-hirsch@womans.org
Contact: Martha Paterson, M.D. 225-924-8947 martha.paterson@womans.org

Locations
United States, Louisiana
Woman's Hospital Recruiting
Baton Rouge, Louisiana, United States, 70817
Principal Investigator: Karen Elkind-Hirsch, PhD         
Sub-Investigator: Martha Paterson, MD         
Sponsors and Collaborators
BC Women's Hospital & Health Centre
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Karen Elkind-Hirsch, Ph.D. Woman's Hospital, Louisiana
Principal Investigator: Martha Paterson, M.D. Woman's Hospital, Louisiana
  More Information

No publications provided

Responsible Party: Karen Elkind-Hirsch, Director of Research, BC Women's Hospital & Health Centre
ClinicalTrials.gov Identifier: NCT01856907     History of Changes
Other Study ID Numbers: RP13-009
Study First Received: May 14, 2013
Last Updated: July 14, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by BC Women's Hospital & Health Centre:
prediabetes
impaired fasting/impaired glucose tolerance
post gestational diabetes
diabetes prevention

Additional relevant MeSH terms:
Sitagliptin
Metformin
Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 02, 2014