Medical Optimization of Management of Type 2 Diabetes Complicating Pregnancy (MOMPOD)
Official Title
Medical Optimization of Management of Type 2 Diabetes Complicating Pregnancy
Acronym
MOMPOD
Organization
University of North Carolina, Chapel HillOTHER
Status Module
Record Verification Date
Apr 2023
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Recommendation by the DSMB that the study be stopped for futility
Expanded Access Info
No
Start Date
May 25, 2017Actual
Primary Completion Date
Jun 15, 2022Actual
Completion Date
Jun 15, 2022Actual
First Submitted Date
May 17, 2016
First Submission Date that Met QC Criteria
Oct 11, 2016
First Posted Date
Oct 13, 2016Estimated
Results Waived
Not provided
Results First Submitted Date
Apr 27, 2023
Results First Submitted that Met QC Criteria
Apr 27, 2023
Results First Posted Date
May 24, 2023Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
May 31, 2023
Last Update Posted Date
Jun 26, 2023Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
University of North Carolina, Chapel HillOTHER
Collaborators
Name
Class
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
NIH
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
Purpose: The objective of this proposal is to study the safety and efficacy of metformin added to insulin for treatment of type 2 diabetes mellitus (T2DM) among pregnant women.
Participants: 950 pregnant women with type 2 diabetes complicating pregnancy from 10 U.S. clinical centers
Procedures (methods): Pregnant women with T2DM between 10 weeks and 22 weeks 6 days and a singleton fetus will be randomized to double-blinded insulin/placebo versus insulin/metformin. Primary outcome is composite adverse neonatal outcome (clinically relevant hypoglycemia, birth trauma, hyperbilirubinemia, stillbirth/neonatal death). Study visits monthly at clinical visits; blood draw at 24-30 weeks, newborn anthropometric measurements at less than 72 hours of life. Maternal and infant outcomes will be chart abstracted.
Detailed Description
Not provided
Conditions Module
Conditions
Diabetes
Pregnancy
Keywords
Metformin
Glucophage
Riomet
Glumetza
Fortamet
Glucophage XR
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
831Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Treatment
Active Comparator
Metformin 1000 mg twice a day
Drug: Metformin
Placebo
Sham Comparator
Placebo, identical to Metformin
Drug: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Metformin
Drug
1000 mg twice a day
Treatment
Glumetza
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Number of Participants With Composite Adverse Neonatal Outcome
Participants with one or more of the following:
capillary blood glucose level of < 30 mg/dL or capillary blood glucose requiring medical treatment, or
Birth trauma (umbilical cord artery pH < 7.0 or shoulder dystocia with brachial plexus injury), or
Hyperbilirubinemia requiring phototherapy, or
Deliver < 37 weeks' gestation, or
Miscarry, are stillborn, experience a neonatal demise, or
Large for gestational age infant (birth weight > 90th percentile for gestational age), or
Small for gestational age infant (birth weight < 10th percentile for gestational age) or low birth weight (< 2500 gm)
An average of 48 hours for term infants and 30 days for preterm infants
Secondary Outcomes
Measure
Description
Time Frame
Number of Participants With Maternal Side Effects
Secondary outcome of maternal side effects were defined as:
clinically relevant hypoglycemia defined as capillary blood glucose < 60 or < 80 with symptoms
GI side effects defined as nausea, vomiting, diarrhea
Throughout study until delivery at 40 weeks gestation
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Maternal age 18-45 years
Singleton pregnancy with no known fetal anomalies
Gestational age between 10weeks 0 days and 22 weeks 6 days by menstrual dating confirmed by ultrasound, or ultrasound alone
Clinical diagnosis of preexisting T2DM requiring medical treatment (oral agent or insulin)
Clinical diagnosis of diabetes diagnosed between 10 weeks and < 20 weeks 6 days gestation
Willing to start insulin therapy and discontinue oral hypoglycemic pills other than study pills
Able to swallow pills
Exclusion Criteria:
Clinical diagnosis of pre-existing renal disease, defined as creatinine > 1.5 mg/dL
Clinical history of lactic acidosis
Known allergy to metformin
Participation in another study that could affect primary outcome
Delivery planned at non-MOMPOD study locations
Unwillingness to use insulin treatment or follow prenatal care doctor's instructions for insulin and blood glucose monitoring
Patel M, Battarbee AN, Refuerzo JS, Zork N, Eichelberger K, Ramos GA, Olson G, Durnwald C, Landon MB, Aagaard KM, Wallace K, Scifres C, Rosen T, Mulla W, Valent A, Longo S, Boggess KA. Association Between Metformin Use in Early Gestational or Type 2 Diabetes in Pregnancy and Preterm Preeclampsia. Obstet Gynecol. 2024 Nov 1;144(5):733-739. doi: 10.1097/AOG.0000000000005720. Epub 2024 Sep 5.
Boggess KA, Valint A, Refuerzo JS, Zork N, Battarbee AN, Eichelberger K, Ramos GA, Olson G, Durnwald C, Landon MB, Aagaard KM, Wallace K, Scifres C, Rosen T, Mulla W, Valent A, Longo S, Young L, Marquis MA, Thomas S, Britt A, Berry D. Metformin Plus Insulin for Preexisting Diabetes or Gestational Diabetes in Early Pregnancy: The MOMPOD Randomized Clinical Trial. JAMA. 2023 Dec 12;330(22):2182-2190. doi: 10.1001/jama.2023.22949.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
Plan to Share IPD
Yes
Description
Not provided
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
Not provided
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Metformin
Metformin 1000 mg twice a day
FG001
Placebo
Placebo, identical to Metformin. Delivered to match active drug
Neonatal fat mass measured by skin-fold thickness (anthropometrics).The circumference of the upper limb is the circumference of the upper arm, and the circumference of the lower limb equals the mean of the circumferences measured at the midthigh and calf. The volume of the subcutaneous layer of fat covering each cylinder is estimated by multiplying the length times the circumference times the layer of fat estimated by the skinfold measures. The triceps skinfold measure is used as an estimate of the fat thickness of the limbs, and the subscapular skinfold measure approximates the fat thickness of the trunk. Total body fat is estimated by summing the volumes of fat covering each of the cylinders and multiplying by 0.9 (the density of fat).
Within 72 hrs of birth
Maternal Safety Based on Treatment Emergent Adverse Events
Adverse maternal outcomes.
An average of 48 hours following delivery
Neonatal Safety Based on Treatment Emergent Adverse Events
Berry DC, Thomas SD, Dorman KF, Ivins AR, de Los Angeles Abreu M, Young L, Boggess K. Rationale, design, and methods for the Medical Optimization and Management of Pregnancies with Overt Type 2 Diabetes (MOMPOD) study. BMC Pregnancy Childbirth. 2018 Dec 12;18(1):488. doi: 10.1186/s12884-018-2108-3.
FG000416 subjects
FG001415 subjects
Randomized
FG000416 subjects
FG001415 subjects
Received Intervention
FG000397 subjects
FG001397 subjects
Liveborn Infants During Study
FG000376 subjects
FG001370 subjects
COMPLETED
FG000386 subjects
FG001382 subjects
NOT COMPLETED
FG00030 subjects
FG00133 subjects
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Metformin
Metformin 1000 mg twice a day
BG001
Placebo
Placebo, identical to Metformin. Delivered to match active drug
BG002
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000397
BG001397
BG002794
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00032.8± 5.5
BG00133.1± 5.7
BG00232.9± 5.6
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG000397
BG001397
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG000203
BG001209
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Region of Enrollment
Count of Participants
Participants
Title
Denominators
Categories
United States
Title
Measurements
BG000397
BG001397
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Number of Participants With Composite Adverse Neonatal Outcome
Participants with one or more of the following:
capillary blood glucose level of < 30 mg/dL or capillary blood glucose requiring medical treatment, or
Birth trauma (umbilical cord artery pH < 7.0 or shoulder dystocia with brachial plexus injury), or
Hyperbilirubinemia requiring phototherapy, or
Deliver < 37 weeks' gestation, or
Miscarry, are stillborn, experience a neonatal demise, or
Large for gestational age infant (birth weight > 90th percentile for gestational age), or
Small for gestational age infant (birth weight < 10th percentile for gestational age) or low birth weight (< 2500 gm)
Modified intent to treat population of all participants who took at least one dose of study agent and had primary outcome data available.
Posted
Count of Participants
Participants
An average of 48 hours for term infants and 30 days for preterm infants
ID
Title
Description
OG000
Metformin
Metformin 1000 mg twice a day
OG001
Placebo
Placebo, identical to Metformin. Delivered to match active drug
Units
Counts
Participants
OG000386
OG001382
Title
Denominators
Categories
Title
Measurements
OG000269
OG001277
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
The sample size gave adequate power over a range of expected primary outcome event rates, with type I error set at 0.044 (reduced from 0.05 for interim analysis), with reasonable power under a conservative scenario assuming that 20% of subjects immediately stopped taking study agent.
Odds Ratio (OR)
0.86
2-Sided
95
0.63
1.19
The odds ratio was calculated and adjusted for study site, timing of diabetes diagnosis, gestational age at randomization stratified at 18 weeks, and baseline maternal BMI.
Superiority
Secondary
Number of Participants With Maternal Side Effects
Secondary outcome of maternal side effects were defined as:
clinically relevant hypoglycemia defined as capillary blood glucose < 60 or < 80 with symptoms
GI side effects defined as nausea, vomiting, diarrhea
Posted
Count of Participants
Participants
Throughout study until delivery at 40 weeks gestation
ID
Title
Description
OG000
Metformin
Metformin 1000 mg twice a day
OG001
Placebo
Placebo, identical to Metformin. Delivered to match active drug
Units
Counts
Participants
OG000
Secondary
Mean Infant Fat Mass
Neonatal fat mass measured by skin-fold thickness (anthropometrics).The circumference of the upper limb is the circumference of the upper arm, and the circumference of the lower limb equals the mean of the circumferences measured at the midthigh and calf. The volume of the subcutaneous layer of fat covering each cylinder is estimated by multiplying the length times the circumference times the layer of fat estimated by the skinfold measures. The triceps skinfold measure is used as an estimate of the fat thickness of the limbs, and the subscapular skinfold measure approximates the fat thickness of the trunk. Total body fat is estimated by summing the volumes of fat covering each of the cylinders and multiplying by 0.9 (the density of fat).
Data are reported for those infants who underwent anthropomorphic measurements.
Posted
Mean
Standard Deviation
kg
Within 72 hrs of birth
ID
Title
Description
OG000
Maternal Metformin
Metformin 1000 mg twice a day
OG001
Maternal Placebo
Placebo, identical to Metformin. Delivered to match active drug
Units
Counts
Participants
Secondary
Maternal Safety Based on Treatment Emergent Adverse Events
Adverse maternal outcomes.
Number of randomized participants who took at least one dose of study agent.
Posted
Count of Participants
Participants
An average of 48 hours following delivery
ID
Title
Description
OG000
Metformin
Metformin 1000 mg twice a day
OG001
Placebo
Placebo, identical to Metformin. Delivered to match active drug
Units
Counts
Participants
OG000
Secondary
Neonatal Safety Based on Treatment Emergent Adverse Events
Adverse neonatal outcomes
Posted
Count of Participants
Participants
up to 28 days of life
ID
Title
Description
OG000
Maternal Metformin
Metformin 1000 mg twice a day
OG001
Maternal Placebo
Placebo, identical to Metformin. Delivered to match active drug
Units
Counts
Participants
OG000
Time Frame
For mothers, AEs were collected from time of randomization to time of hospital discharge after delivery, an average of 48 hours following delivery. For infants, from birth through 28 days of age.
Description
Not provided
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Maternal Metformin
Metformin 1000 mg twice a day
2
397
113
397
54
397
EG001
Fetus of Mother Receiving Metformin
Fetuses in utero to mothers assigned metformin 1000 mg twice a day
10
397
0
397
0
397
EG002
Infants Born to Mothers Receiving Metformin
Infants born to mothers assigned metformin 1000 mg twice a day
1
376
81
376
151
376
EG003
Maternal Placebo
Placebo, identical to Metformin. Delivered to match active drug
1
397
111
397
57
397
EG004
Fetus of Mother Receiving Placebo
Fetuses in utero to mothers assigned placebo delivered to match active drug
10
397
0
397
0
397
EG005
Infants Born to Mothers Receiving Placebo
Infants born to mothers assigned placebo, identical to metformin, delivered to match active drug