- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02338193
Dapagliflozin and Metformin,Alone and in Combination, in Overweight/Obese Prior GDM Women (DAPA-GDM)
A Randomized Study Evaluating Dapagliflozin and Metformin, Alone and in Combination, in Overweight Women With a Recent History of Gestational Diabetes Mellitus: Effects on Anthropometric Measurements and Cardiometabolic Abnormalities
Study Overview
Status
Intervention / Treatment
Detailed Description
Following written consent, all study patients will undergo the following clinical, metabolic and laboratory evaluations before and during treatment. To ensure that patients remain unidentified, all study subjects will be assigned an individual study identifier which includes the study acronym, patient initials, and unique number. All blood samples will be obtained and results identified and reported using this unique study identifier. A full physical examination will be performed and vital signs (blood pressure, respiration and temperature) determined. Trained personnel using standardized protocols at the baseline and follow-up examination will obtain anthropometric measurements and blood specimens. Absolute body weight, height, waist and hip circumference, body fat distribution (waist/hip {WHR}) and waist/height ratio ({WHtR}) and blood pressure (BP) will be determined. Body weight will be measured to the nearest 0.1 kg using a calibrated digital scale with participants in light clothing and no shoes. Height will be measured to the nearest centimeter. The total body adiposity (total fatness), defined as the accumulation of body fat without regard to regional distribution, will be expressed as BMI and calculated as weight (kg)/ height (m) 2. The circumference measurements will be taken in the upright position using a 15-mm width flexible metric tape held close to the body but not tight enough to indent the skin. Waist circumference (WC) will be measured at the narrowest level midway between the lowest ribs and the iliac crest and hip circumference measured at the widest level over the buttocks while the subjects are standing and breathing normally. The WHR and WHtR will be calculated for measure of body fat distribution.
All patients will randomly be assigned to one of 3 medication treatment groups-- dapagliflozin-metformin (DAP-MET; 5 mg DAP/ MET 1000 mg BID), metformin XR (MET 1000 mg BID) or dapagliflozin (DAP 10 mg QD); all subjects will be allocated to one of these 3 groups based on computer-generated random numbers using a block randomization method. Oral glucose tolerance tests (OGTTs) with glucose (G) and insulin (I) measured at 0, 30, 60, and 120 after glucose load to assess diabetes, fasting (FBG) and mean blood glucose (MBG) concentrations, insulin resistance and pancreatic ß-cell function will be performed prior to randomization and at 20-24 weeks after full doses of study medications are reached. Mean blood glucose (MBG) concentrations will be calculated by summing glucose values obtained at 0,30,60 and 120 minutes during the OGTT and dividing by 4. At the initial lab evaluation, creatinine and calculated eGFR, TSH, and ß-hCG will be determined for study inclusion. Baseline blood samples will also be analyzed for lipid profiles and liver enzymes.
All patients will receive the same counseling concerning the benefits of lifestyle modification through diet and exercise. The patients will be also encouraged to increase daily exercise (such as walking, using stairs), although this will not be formally assessed. The participants will receive further encouragement to adhere to the regime during follow-up phone calls. Side effects of the treatment and reason for any withdrawals from the study will be recorded.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Louisiana
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Baton Rouge, Louisiana, United States, 70815
- Woman's Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
• Overweight/obese (BMI >25) females 18 years to 45 years of age, who experienced gestational diabetes (GDM) during recent (within 12 months) pregnancy
- postpartum metabolic abnormalities determined by a 75 g oral glucose tolerance test (Inclusive of prior GDM women with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both (IFG/IGT) postpartum)
- Completed lactation
- Using adequate contraception during study period unless sterilized
- 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), gallstones, abnormal liver function tests or renal impairment (elevated serum creatinine levels or abnormal creatinine clearance
- Presence of significant systemic disease, heart problems including congestive heart failure, history of pancreatitis, or diabetes mellitus (Type 1 or 2)
- Renal impairment (e.g., serum creatinine levels ≥1.4 mg/dL for women, or eGFR <60)
- Significantly elevated triglyceride levels (fasting triglyceride > 400 mg %)
- Untreated or poorly controlled hypertension (sitting blood pressure >160/95mm Hg)
- Prior history of a malignant disease requiring chemotherapy
- Known hypersensitivity or contraindications to use of insulin sensitizers such as metformin or thiazolidinediones
- History of hypersensitivity reaction to dapagliflozin or other SGLT2 inhibitors (e.g. anaphylaxis, angioedema, exfoliative skin conditions)
- Current use of metformin, thiazolidinediones, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT2 inhibitors or weight loss medications (prescription or OTC)
- Uncontrolled thyroid disease (documented normal TSH) or hyperprolactinemia
- Liver enzymes (serum alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST] ) levels exceeding more than twice normal lab values
- Use of drugs known to exacerbate glucose tolerance
- History of diabetes or prior use of medications to treat diabetes except GDM
- Currently lactating
- Eating disorders (anorexia, bulimia) or gastrointestinal disorders
- Suspected pregnancy (documented negative serum pregnancy test within 72 hours before first dose of study drug), desiring pregnancy in next 6 months, breastfeeding, or known pregnancy in last 2 months
- Active or prior history of substance abuse (smoke or tobacco use within past 3 years) or significant intake of alcohol or history of alcoholism
- Patient not willing to use adequate contraception during study period and up to 4 weeks after last dose of study drug (unless sterilized).
- Debilitating psychiatric disorder such as psychosis or neurological condition that might confound outcome variables
- Inability or refusal to comply with protocol
- Not currently participating or having participated in an experimental drug study in previous three months
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: DAPA/MET Extended Release (XR)
Dapagliflozin plus metformin XR- 5 mg/1000 mg with meal for 4 weeks DAPA/MET XR- 5mg/1000 mg BID final dose for 20 weeks
|
final dose- 5 mg dapagliflozin/1000 mg glucophage XR BID for 20-24 weeks
Other Names:
|
Active Comparator: Dapaglifloxin
Dapagliflozin- 10 mg once daily before first meal for 24 weeks
|
10 mg dapagliflozin QD for 20-24 weeks
Other Names:
|
Active Comparator: Metformin XR
Metformin XR with 500 mg once a day for 2 weeks, followed by 500 mg twice a day for 2 weeks, followed by 500 mg in the morning (AM), 1000 mg in the evening ( PM) for 2 weeks, with 1000 mg twice a day as the final dose for 20 weeks
|
1000 mg Metformin XR BID for 20-24 weeks
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Body Weight
Time Frame: Change from baseline (time 0) to study end (24 weeks)
|
Change in absolute body weight with combination therapy compared to monotherapy from baseline to week 24
|
Change from baseline (time 0) to study end (24 weeks)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Percent Body Weight
Time Frame: Change from baseline (time 0) to study end (24 weeks)
|
Change in percent body weight with combination therapy compared to monotherapy from baseline to week 24
|
Change from baseline (time 0) to study end (24 weeks)
|
Body Mass Index (BMI)
Time Frame: 24 weeks of treatment
|
BMI (measure of overall adiposity) in combination therapy compared to monotherapy after 24 weeks of treatment
|
24 weeks of treatment
|
Waist Circumference (WC)
Time Frame: 24 weeks of treatment
|
Waist size (measure of truncal adiposity)with combination therapy compared to monotherapy after 24 weeks of treatment
|
24 weeks of treatment
|
Waist- to -Hip Ratio (WHR; Measure of Central Adiposity)
Time Frame: 24 weeks of treatment
|
Waist-to-hip ratio with combination therapy compared to monotherapy after 24 weeks of treatment
|
24 weeks of treatment
|
Waist-to-height Ratio (WHtR)
Time Frame: 24 weeks of treatment
|
Waist divided by height a( measure of central adiposity) with combination therapy compared to monotherapy after 24 weeks of therapy
|
24 weeks of treatment
|
Diastolic Blood Pressure (DBP)
Time Frame: 24 weeks of treatment)
|
Diastolic blood pressure with combination therapy compared to monotherapy after 24 weeks of treatment
|
24 weeks of treatment)
|
Systolic Blood Pressure (SBP)
Time Frame: 24 weeks of treatment
|
Systolic blood pressure with combination therapy compared to monotherapy after 24 weeks of therapy
|
24 weeks of treatment
|
Liver Enzymes
Time Frame: 24 weeks of treatment
|
ALT/AST ratio with combination therapy compared to monotherapy after 24 weeks of treatment
|
24 weeks of treatment
|
Total Cholesterol Levels (CHOL)
Time Frame: 24 weeks of treatment
|
Cholesterol levels with combination therapy compared to monotherapy after 24 weeks of treatment
|
24 weeks of treatment
|
Triglyceride (TRG) Levels
Time Frame: 24 weeks of treatment
|
Triglyceride levels with combination therapy compared to monotherapy after 24 weeks of treatment
|
24 weeks of treatment
|
Fasting Blood Glucose (FBG)
Time Frame: 24 weeks of treatment
|
Fasting blood glucose levels with combination therapy compared to monotherapy after 24 weeks of treatment
|
24 weeks of treatment
|
Mean Blood Glucose (MBG) During an OGTT
Time Frame: 24 weeks of treatment
|
Mean blood glucose after glucose load with combination therapy compared to monotherapy after 24 weeks of treatment
|
24 weeks of treatment
|
Fasting Insulin Sensitivity (HOMA-IR)
Time Frame: 24 weeks of treatment
|
HOMA index of insulin resistance calculated from fasting insulin and glucose with combination therapy compared to monotherapy after 24 weeks of treatment
|
24 weeks of treatment
|
Matsuda Sensitivity Index (SI OGTT)
Time Frame: 24 weeks of treatment
|
Surrogate measure of insulin sensitivity derived from OGTT with combination therapy compared to monotherapy after 24 weeks of treatment
|
24 weeks of treatment
|
First Phase Insulin Secretion (IGI/HOMA-IR)
Time Frame: 24 weeks of treatment
|
Corrected early insulin response to glucose challenge [(insulinogenic index (IGI)/ divided by fasting insulin resistance index (HOMA-IR)] with combination therapy compared to monotherapy after 24 weeks of treatment
|
24 weeks of treatment
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Karen E Elkind-Hirsch, PhD, Woman's Hospital, Louisiana
- Principal Investigator: Renee Harris, MD, Woman's Hospital, Louisiana
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- RP-14-012
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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