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Empagliflozin and the Preservation of Beta-cell Function in Women With Recent Gestational Diabetes (EMPA post-GDM)

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ClinicalTrials.gov Identifier: NCT03215069
Recruitment Status : Not yet recruiting
First Posted : July 12, 2017
Last Update Posted : July 12, 2017
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
Mount Sinai Hospital, Canada

Brief Summary:
Double-blind, parallel arm, randomized controlled trial, in which non-lactating women with recent GDM who are between 6 to 36 months postpartum to be randomized to either empagliflozin 10 mg daily or matching placebo. The duration of treatment will be 48-weeks. Beta-cell function will be assessed by Insulin Secretion-Sensitivity Index-2 (ISSI-2), measured on oral glucose tolerance test (OGTT) at baseline, 24-weeks, 48-weeks, and after a 4-week washout.

Condition or disease Intervention/treatment Phase
Gestational Diabetes Drug: Empagliflozin 10 MG Drug: Placebo oral capsule Phase 3

Detailed Description:
Gestational diabetes mellitus (GDM), defined as glucose intolerance of varying severity with first onset and recognition in pregnancy, identifies a population of women who are at high risk for the future development of type 2 diabetes (T2DM). This risk of T2DM is mediated by the progressive deterioration of insulin secretion by the pancreatic beta-cells in the years after delivery, a pathologic process that current anti-diabetic therapies have not been shown to modify. Importantly, since very mild glycemia has deleterious but reversible effects on insulin secretion ("glucotoxicity"), the beta-cell dysfunction of women with recent GDM should have a prominent reversible component that potentially could be mitigated through the elimination of glucotoxicity. In this context, the sodium glucose co-transporter-2 (SGLT-2) inhibitor empagliflozin is a novel anti-diabetic therapy that specifically alleviates glucotoxicity and thus may be able to preserve beta-cell function. Coupled with its capacity to induce weight loss with low risk of hypoglycemia, empagliflozin could be an ideal therapy for diabetes prevention in women with recent GDM. Specifically, by eliminating glucotoxicity, SGLT-2 inhibition could enable the preservation of beta-cell function and thereby prevent the development of incident T2DM in this high-risk population. Thus, a double-blind, parallel arm, randomized controlled trial, in which non-lactating women with recent GDM who are between 6 to 36 months postpartum to be randomized to either empagliflozin 10 mg daily or matching placebo is proposed. The duration of treatment will be 48-weeks. Beta-cell function will be assessed by Insulin Secretion-Sensitivity Index-2 (ISSI-2), measured on oral glucose tolerance test (OGTT) at baseline, 24-weeks, 48-weeks, and after a 4-week washout.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Empagliflozin and the Preservation of Beta-cell Function in Women With Recent Gestational Diabetes
Estimated Study Start Date : September 1, 2017
Estimated Primary Completion Date : September 1, 2021
Estimated Study Completion Date : September 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Empagliflozin
Empagliflozin 10 mg PO daily
Drug: Empagliflozin 10 MG
Empagliflozin 10 mg PO daily

Placebo Comparator: Placebo
Matched placebo PO daily
Drug: Placebo oral capsule
Placebo PO daily




Primary Outcome Measures :
  1. Baseline-adjusted ISSI-2 at 48-weeks [ Time Frame: 48-weeks ]
    The primary outcome will be measured by ISSI-2. ISSI-2 is a validated OGTT-derived measure of beta-cell function analogous to the disposition index obtained from the intravenous glucose tolerance test. ISSI-2 is defined as the product of (i) insulin secretion measured by the ratio of the area-under-the-insulin-curve (AUCins) to the area-under-the-glucose curve (AUCgluc) and (ii) insulin sensitivity measured by the Matsuda index.


Secondary Outcome Measures :
  1. Glucose tolerance status at 48-weeks [ Time Frame: 48-weeks ]
    Prevalence of dysglycemia on the OGTT at this visit.


Other Outcome Measures:
  1. Baseline-adjusted ΔISR0-120/Δgluc0-120 × Matsuda index at 48 weeks [ Time Frame: 48-weeks ]
    and insulinogenic index/HOMA-IR.

  2. Baseline-adjusted insulinogenic index/HOMA-IR at 48-weeks [ Time Frame: 48-weeks ]
    Beta-cell function assessed by ΔISR0-120/Δgluc0-120 × Matsuda index at 48-weeks

  3. Body mass index at 48-weeks [ Time Frame: 48-weeks ]
  4. Insulin sensitivity at 48 weeks. [ Time Frame: 48-weeks ]
    Insulin sensitivity will be measured by Matsuda index on OGTT

  5. Central abdominal fat mass at 48 weeks [ Time Frame: 48-weeks ]
    Central abdominal fat mass will be measured by DXA assessment at L2-L4

  6. Quality of life at 48 weeks [ Time Frame: 48-weeks ]
    Quality of life will be assessed annually by the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36).



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Ages Eligible for Study:   20 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Women with history of gestational diabetes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women with recent gestational diabetes who are between 6-36 months postpartum inclusive and no longer breastfeeding
  • Age 20 - 50 years inclusive
  • Negative pregnancy test at recruitment

Exclusion Criteria:

  • Current breastfeeding
  • Current diabetes or treatment with any anti-diabetic medication
  • Involvement in any other clinical study requiring drug therapy
  • Hypersensitivity to empagliflozin or the formulations of this product
  • Any history of diabetic ketoacidosis
  • History of recurrent urinary infection (i.e. more than 2 episodes over the past year).
  • Renal dysfunction as evidenced by estimated glomerular filtration rate < 45 ml/min by Modification of Diet in Renal Disease (MDRD) formula
  • Hepatic disease considered to be clinically significant (includes jaundice, chronic hepatitis, or previous liver transplant) or transaminases >2.5X the upper limit of normal
  • Malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy within the previous 5 years (with the exception of basal cell skin cancer)
  • Pregnancy or unwillingness to use reliable contraception. Women should not be planning pregnancy for the duration of the study or the first 3 months after the study. Reliable contraception includes the following: birth control pill, intra-uterine device, abstinence, tubal ligation, partner vasectomy, or condoms with spermicide.
  • Any other factor likely to limit adherence to the study, in the opinion of the investigators

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03215069


Contacts
Contact: Caroline Kramer, MD PhD 4165864800 ext 7628 Caroline.Kramer@sinaihealthsystem.ca

Sponsors and Collaborators
Mount Sinai Hospital, Canada
Boehringer Ingelheim

Responsible Party: Mount Sinai Hospital, Canada
ClinicalTrials.gov Identifier: NCT03215069     History of Changes
Other Study ID Numbers: 16-0226-A
First Posted: July 12, 2017    Key Record Dates
Last Update Posted: July 12, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

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