Gestational DiabetesPhase 3NCT03651531
Comparison of Insulin Alone to Insulin With Metformin to Treat Gestational Diabetes Mellitus
A Phase 3 study testing Insulin and Metformin in people with Gestational Diabetes, run by Women and Infants Hospital of Rhode Island at 1 site in United States.
Trial summary
This study is a prospective, unmasked randomized clinical trial comparing the use of insulin vs combination insulin and metformin for treatment in women diagnosed with gestational diabetes mellitus (GDM). Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Gestational Diabetes
- What is being tested?
- Insulin and Metformin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Jan 2018to 30 Jul 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to read and write English and/or Spanish and give written consent
- Diagnosis of GDM, defined as an abnormal glucose tolerance test performed after 12 weeks gestation using 1 of the 2 criteria below:
- 50 gram 1 hour oral diabetes screening testing yielding a result of > 200 mg/dL
- A 100 gram 3 hour oral glucose tolerance testing yielding >2 abnormal values (normal values defined as fasting blood glucose < 95, 1 hour < 180, 2 hour < 155 and 3 hour < 140)
- Singleton gestation
- Gestational age between 12 and 34 weeks and 6 days determined by last menstrual period (LMP) confirmed by ultrasound using criteria set forth by the ACOG (Committee on Obstetric Practice). If LMP is unknown then gestational age must be set by ultrasound prior to 20 weeks gestation.
Who cannot join
- Pre-existing DM either by diagnosis preceding pregnancy or hemoglobin A1c >6.5 collected during the current pregnancy
- Uncontrolled chronic hypertension, as this may alter maternal and perinatal outcomes measured.
- Multiple gestations
- Major fetal anomalies anticipated to require NICU admission
- Contraindication to metformin (allergy, history of lactic acidosis, pre-existing renal disease (Cr >1.5 mg/dL), active liver disease, current alcohol abuse).
- Vitamin B12 deficiency, as metformin reduces intestinal absorption of vitamin B12
- Medications known to effect glucose metabolism other than insulin and metformin as this may mask any effect between the two treatments.
- Known inability to tolerate metformin.
Trial locations and contacts
1 site in 1 country.
United States1 site
Women & Infants Hospital
Providence, Rhode Island, 02905
About this study
This study is a prospective, unmasked randomized clinical trial comparing the use of insulin vs combination insulin and metformin for treatment in women diagnosed with gestational diabetes mellitus (GDM). The investigator's hypothesis is that the combination of metformin and insulin will be superior to insulin alone to achieve tight glucose control during pregnancy.
Read the detailed description
The objective of this study is to compare the effectiveness of insulin alone vs the combination of insulin and metformin in treating patients with gestational diabetes (GDM). Currently, outside of pregnancy, the treatment of type 2 diabetes mellitus (T2DM) with both metformin and insulin is superior to using insulin alone. In pregnancy, insulin alone has traditionally been used, though some advocate the use of metformin alone as primary therapy. There have been no trials published to date specifically comparing combination therapy to insulin alone. Our hypothesis is that the combination of metformin and insulin will improve overall control of blood glucose, the improvement of which has been demonstrated to improve maternal and neonatal outcomes. Control of blood glucose will be determined by hemoglobin A1c at the time of delivery.
- Conditions
- Gestational Diabetes
- Keywords
- metformin
- Medical subject headings
- Diabetes, Gestational
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InsulinDrug
Weight based insulin will be calculated using 0.7 units/kg/day in the first trimester, 0.8 units/kg/day in the second trimester and 1 units/kg/day in the third trimester. This total insulin will then be divided into short acting insulin and intermediate acting insulin per provider discretion.
MetforminDrug
Will be initiated at dose of 500 mg twice daily. If glycemic control is suboptimal, the dose of metformin will be increased to 1000 mg twice a day. Metformin will be titrated prior to increases in insulin.
| Study group | Role | What they receive |
|---|---|---|
| insulin | Active comparator | Not described Receives: Drug: Insulin |
| insulin and metformin | Active comparator | Not described Receives: Drug: Insulin; Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hgb A1c
Hgb A1c test
Measured: collected at the time of delivery
Secondary outcomes (15)
Total daily dose of insulin
Total daily dose of insulin at the end of pregnancy
Measured: Will be recorded on hospital admission for delivery
Glucose control
Average of fasting and 2 hour postprandial glucose values
Measured: patients will collect glucose values fasting and 2 hrs postprandial every day from enrollment until delivery.
Incidence of maternal hypoglycemia
episodes of maternal hypoglycemia defined as glucose ≤70 mg/dL
Measured: patients will be screened weekly for episodes of hypoglycemia until delivery
Change in hemoglobin A1c over the course of the pregnancy
If baseline hemoglobin A1c was collected as part of routine care prior to enrollment, this value will be compared to the hemoglobin A1c collected at delivery
Measured: hemoglobin A1c will be collected at delivery (per above) and comparison performed after collection
Incidence of maternal side effects
maternal reported medication side effects (i.e. nausea, vomiting, diarrhea)
Measured: Will be assessed weekly until delivery
Treatment acceptability
determined using Diabetes Treatment Satisfaction Questionnaire. Survey includes 8 questions that are answered on a scale of 0-6; 0 indicating the least and 6 the highest level of satisfaction. The individual questions will be compared. Total satisfaction will also be compared by summing the responses to all 8 questions on a composite scale of 0-48
Measured: Will be collected postpartum after delivery
Maternal weight gain
weight gain through pregnancy
Measured: This will be calculated as the difference from the weight measured at the inital prenatal visit (the specific timing of which is patient dependant) and at the time of admission for delivery
Incidence of hypertensive disorder of pregnancy
gestational HTN, superimposed pre-eclampsia, pre-eclampsia-eclampsia
Measured: from enrollment through study completion (30 days after delivery)
Incidence of composite of adverse maternal outcomes
death, ICU admission, postpartum hemorrhage, blood transfusion, organ failure, chorioamnionitis/endometritis
Measured: from enrollment through study completion (30 days after delivery)
Breast feeding status
Whether patient is breast feeding or bottle feeding upon discharge from the hospital after delivery
Measured: Will be recorded at the time of hospital discharge after delivery (typically 2-4 days after delivery)
Mode of delivery
Mode of delivery
Measured: recorded at time of delivery
Gestational age at delivery
Gestational age at delivery
Measured: recorded at time of delivery
Infant birthweight (using age/sex matched percentiles)
Infant birthweight (using age/sex matched percentiles)
Measured: measured at time of birth
Incidence of composite neonatal morbidity
Presence of any of the following: NICU admission, hypoglycemia, hyperbilirubinemia, birth trauma, stillbirth, respiratory distress syndrome, sepsis, neonatal death prior to discharge, 5 minute Apgar score < 7, umbilical artery cord pH <7.10
Measured: from delivery through study completion (30 days after delivery)
Incidence neonatal hypoglycemia
hypoglycemia requiring intravenous treatment
Measured: from delivery through study completion (30 days after delivery)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2018
- Study start3 Jan 2018
- Primary completion30 Jul 2019
- Study completion30 Jul 2019
Why it stopped: Trial halted early due to limited ability to recruit participants
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Gestational DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Women and Infants Hospital of Rhode Island
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christopher Nau, MD, Principal investigator, Women & Infants HospitalErika Werner, Principal investigator, Women & Infants Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03651531
- Sponsor's protocol ID
- 1099865-3
- Status last verified
- Jul 2020
- First submitted
- 12 Jun 2018
- Last updated
- 24 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Committee Opinion No 700: Methods for Estimating the Due Date. Obstet Gynecol. 2017 May;129(5):e150-e154. doi: 10.1097/AOG.0000000000002046.
PubMed 28426621
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Insulin Alone to Insulin With Metformin to Treat Gestational Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT03651531
- Acronym / sponsor ID
- 1099865-3
- Conditions
- Gestational Diabetes
- Keywords
- metformin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Trial halted early due to limited ability to recruit participants
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Women and Infants Hospital of Rhode IslandUniversity, hospital or other
- Study start
- 3 Jan 2018 (actual)
- Primary completion
- 30 Jul 2019 (actual)
- Study completion
- 30 Jul 2019 (actual)
- First posted
- 29 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a prospective, unmasked randomized clinical trial comparing the use of insulin vs combination insulin and metformin for treatment in women diagnosed with gestational diabetes mellitus (GDM). The investigator's hypothesis is that the combination of metformin and insulin will be superior to insulin alone to achieve tight glucose control during pregnancy.
Detailed description
The objective of this study is to compare the effectiveness of insulin alone vs the combination of insulin and metformin in treating patients with gestational diabetes (GDM). Currently, outside of pregnancy, the treatment of type 2 diabetes mellitus (T2DM) with both metformin and insulin is superior to using insulin alone. In pregnancy, insulin alone has traditionally been used, though some advocate the use of metformin alone as primary therapy. There have been no trials published to date specifically comparing combination therapy to insulin alone. Our hypothesis is that the combination of metformin and insulin will improve overall control of blood glucose, the improvement of which has been demonstrated to improve maternal and neonatal outcomes. Control of blood glucose will be determined by hemoglobin A1c at the time of delivery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| insulin | Active comparator | Drug: Insulin |
| insulin and metformin | Active comparator | Drug: Insulin, Drug: Metformin |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Able to read and write English and/or Spanish and give written consent
- Diagnosis of GDM, defined as an abnormal glucose tolerance test performed after 12 weeks gestation using 1 of the 2 criteria below:
- 50 gram 1 hour oral diabetes screening testing yielding a result of > 200 mg/dL
- A 100 gram 3 hour oral glucose tolerance testing yielding >2 abnormal values (normal values defined as fasting blood glucose < 95, 1 hour < 180, 2 hour < 155 and 3 hour < 140)
- Singleton gestation
Key exclusion criteria (8 listed)
- Pre-existing DM either by diagnosis preceding pregnancy or hemoglobin A1c >6.5 collected during the current pregnancy
- Uncontrolled chronic hypertension, as this may alter maternal and perinatal outcomes measured.
- Multiple gestations
- Major fetal anomalies anticipated to require NICU admission
- Contraindication to metformin (allergy, history of lactic acidosis, pre-existing renal disease (Cr >1.5 mg/dL), active liver disease, current alcohol abuse).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| InsulinWeight based insulin will be calculated using 0.7 units/kg/day in the first trimester, 0.8 units/kg/day in the second trimester and 1 units/kg/day in the third trimester. This total insulin will then be divided into short acting insulin and intermediate acting insulin per provider discretion. | Drug | insulin, insulin and metformin |
| MetforminWill be initiated at dose of 500 mg twice daily. If glycemic control is suboptimal, the dose of metformin will be increased to 1000 mg twice a day. Metformin will be titrated prior to increases in insulin. | Drug | insulin and metformin |
Primary outcome
Hgb A1c
Time frame: collected at the time of delivery
Hgb A1c test
15 secondary outcomes
Total daily dose of insulin
Time frame: Will be recorded on hospital admission for delivery
Glucose control
Time frame: patients will collect glucose values fasting and 2 hrs postprandial every day from enrollment until delivery.
Incidence of maternal hypoglycemia
Time frame: patients will be screened weekly for episodes of hypoglycemia until delivery
Change in hemoglobin A1c over the course of the pregnancy
Time frame: hemoglobin A1c will be collected at delivery (per above) and comparison performed after collection
Incidence of maternal side effects
Time frame: Will be assessed weekly until delivery
Treatment acceptability
Time frame: Will be collected postpartum after delivery
Maternal weight gain
Time frame: This will be calculated as the difference from the weight measured at the inital prenatal visit (the specific timing of which is patient dependant) and at the time of admission for delivery
Incidence of hypertensive disorder of pregnancy
Time frame: from enrollment through study completion (30 days after delivery)
Incidence of composite of adverse maternal outcomes
Time frame: from enrollment through study completion (30 days after delivery)
Breast feeding status
Time frame: Will be recorded at the time of hospital discharge after delivery (typically 2-4 days after delivery)
Mode of delivery
Time frame: recorded at time of delivery
Gestational age at delivery
Time frame: recorded at time of delivery
Infant birthweight (using age/sex matched percentiles)
Time frame: measured at time of birth
Incidence of composite neonatal morbidity
Time frame: from delivery through study completion (30 days after delivery)
Incidence neonatal hypoglycemia
Time frame: from delivery through study completion (30 days after delivery)
Results and safety
The study was stopped early (reason given: Trial halted early due to limited ability to recruit participants). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2020.
- Background: PubMed 28426621Committee Opinion No 700: Methods for Estimating the Due Date. Obstet Gynecol. 2017 May;129(5):e150-e154. doi: 10.1097/AOG.0000000000002046.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher Nau, MD principal investigator
Women & Infants Hospital
Erika Werner principal investigator
Women & Infants Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Insulin and Metformin in people with Gestational Diabetes, run by Women and Infants Hospital of Rhode Island at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Trial halted early due to limited ability to recruit participants). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hgb A1c (time frame: collected at the time of delivery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03651531, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2020.