Acarbose and Prandial Insulin for the Treatment of Gestational Diabetes Mellitus. (ACARB-GDM)
Primary Purpose
Gestational Diabetes Mellitus in Pregnancy
Status
Active
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Acarbose
Prandial insulin
Sponsored by
About this trial
This is an interventional treatment trial for Gestational Diabetes Mellitus in Pregnancy focused on measuring Diabetes, Pregnancy, Gestational, Acarbose
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years
- Singleton pregnancy
- GDM diagnosed during pregnancy according to IADPSG criteria
- Self-monitoring of blood glucose
- After at least 7 days of dietary and lifestyle measures, unreached post-prandial glucose control
- 14-37 (+ 6 days) amenorrhea weeks at the time of randomization
- Signed informed consent
Exclusion Criteria:
- Prandial insulin use before randomization during this pregnancy
- Use of other oral hypoglycemic agents during this pregnancy
- Multiple pregnancy
- Known hepatic insufficiency
- Long time corticosteroid treatment
- Pre-existing diabetes in pregnancy
- Overt diabetes diagnosed during pregnancy (IADPSG criteria)
- Lack of Social Insurance
- Insufficient understanding
- Participant in another investigational drug study at inclusion visit
- Contraindications of acarbose
- Fetal malformation diagnosed by previous fetal ultrasound
Sites / Locations
- Jean Verdier Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
acarbose
prandial insulin
Arm Description
The women will receive acarbose with a progressive increase of dose according to post prandial glucose values and digestive tolerance, with a maximal dose of 3 x 100 mg /day
The women will receive prandial insulin according to usual practice (routine care according to French recommendations): before each meal, with dose titration according to post prandial values.
Outcomes
Primary Outcome Measures
Composite endpoint: birth weight ≥ 90th percentile for gestational age (large for gestational age: LGA) and/or neonatal hypoglycemia and/or shoulder dystocia and/or birth injury.
LGA defined as birth weight greater than the 90th percentile for a standard French population
Neonatal hypoglycemia defined as at least a blood glucose value less than a 2.0 mmol/l during the two first days of life;
Shoulder dystocia, defined as vaginal cephalic delivery that requires additional obstetric manoeuvres to deliver the fetus after the head has delivered and gentle traction has failed. We will only consider rotational maneuvers such as Rubin II or Woods corkscrew or Jaquemier maneuvers
Birth injury defined as plexus injury or clavicle fracture.
Secondary Outcome Measures
GLUCOSE CONTROL: Capillary glucose levels
The women will be asked to perform 6 measures a day. Capillary glucose values will be retrieved from the glucose meter, and if not available, from the woman's diary.
GLUCOSE CONTROL: HbA1c
Centralized measurement
GLUCOSE CONTROL: Need for and dose/day of basal and prandial insulin in both arms
This information will be retrieved from the glucose meter, and if not available, from the woman's diary.
Neonatal complications : Birth weight and height,
Birth weight ≥ 4000g Birth weight ≥ 4500g
Neonatal complications : Small for gestational age infant
SGA: birth weight lower than the 10th percentile for a standard French population
Maternal complications : Preeclampsia
Preeclampsia (blood pressure ≥ 140/90 mmHg on two measurements four hours apart and proteinuria of at least 300 mg/24 hours or 3+ or more on dipstick testing or proteinuria/creatininuria >30 in a random urine sample).
Maternal complications : Pregnancy-induced hypertension
In women with no known hypertension before pregnancy, blood pressure ≥ 140/90 mmHg on two measurements four hours apart without proteinuria and having needed to begin anti-hypertensive therapy
Neonatal complications : Preterm delivery
Late preterm infant (between 32 and 37 completed weeks' gestation)
Very preterm infant (28-31 completed weeks' gestation)
Extreme preterm infant (less than 28 completed weeks' gestation)
Neonatal complications : Low Apgar score
5-min Apgar score < 7
Neonatal complications : Neonatal respiratory distress syndrome
based on the clinical course, chest X-ray finding, blood gas and acid-base values
Neonatal complications : Intrauterine fetal or neonatal death;
These endpoints will be extracted from the women' charts
Acceptance/satisfaction of two strategies : -Quality of life -Satisfaction questionnaires
Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36)
- use of analogic scales
Side effects of drugs : Maternal hypoglycemia
Severe hypoglycemia: requiring assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma/capillary glucose to normal is considered sufficient evidence that the event was induced by a low plasma/capillary glucose concentration.
event during which typical symptoms of hypoglycemia are accompanied by a measured capillary glucose concentration <70 mg/dL (<3.9 mmol/L).
Asymptomatic hypoglycemia: event not accompanied by typical symptoms of hypoglycemia but with a measured capillary glucose concentration <60 mg/dL (<3.3 mmol/L).
Gastro-intestinal side effects
The events occuring during the last 14 days of pregnancy or gastro-intestinal side effects leading to treatment withdrawl
Results of oral glucose tolerance test and HbA1c measurement
Test will be performed by the women before follow up visit
Infant anthropometrics.
These data will be collected from children's health record
Conservation of serum and plasma; cord fluid. The samples may be used for further analyses ancillary studies and which could be beneficial for GDM care based on evolution in scientific knowledge.
The blood samples will be collected at the same time as the sample routinely collected just before delivery for irregular agglutinin test measurement.
Cord fluid will be collected
Full Information
NCT ID
NCT03380546
First Posted
November 7, 2017
Last Updated
April 28, 2023
Sponsor
Assistance Publique - Hôpitaux de Paris
1. Study Identification
Unique Protocol Identification Number
NCT03380546
Brief Title
Acarbose and Prandial Insulin for the Treatment of Gestational Diabetes Mellitus.
Acronym
ACARB-GDM
Official Title
Non-inferiority Between Acarbose and Prandial Insulin for the Treatment of Gestational Diabetes Mellitus: a Randomized Multicenter and Prospective Trial. ACARB-GDM Study.
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 4, 2018 (Actual)
Primary Completion Date
November 30, 2023 (Anticipated)
Study Completion Date
March 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Caring for women with gestational diabetes mellitus (GDM) is very time-consuming. Therapeutic strategy includes dietary and lifestyle measures and additional insulin therapy for 15 to 40% of the women with GDM if the glycemic targets are not achieved after a period of 1 to 2 weeks of diet. Insulin therapy is imperfect for the following main reasons: need for education (i.e. subcutaneous administration, dose titration), hypoglycemia and weight gain, limited acceptance and high cost. Psychosocial deprivation is associated with more cases of GDM and health accessibility may be unequal.
Glucosidase inhibitors (acarbose) reduce intestinal absorption of starch and reduce the rate of complex carbohydrate digestion. It mainly lowers postprandial glucose values and is used in type 2 diabetes for a long time. Less than 2% of a dose is absorbed as active drug in adults, with 34% of the metabolites found in the systemic circulation. Doses of up to 9 and 32 times the human dose were not teratogenic in pregnant rats or rabbits. Limited but reassuring data during pregnancy are available. Acarbose was well tolerated (little gestational weight gain, no hypoglycemia) with digestive discomfort in some women, balanced by treatment satisfaction as compared with insulin injections. Our hypothesis is that treatment aiming to control postprandial glucose values with acarbose as compared with prandial insulin injection will be as efficient and safe, but more convenient and less expensive.
Detailed Description
Phase III study. Prospective, multicenter, non-inferiority, randomized, open-labelled and controlled study with two arms.
In the 31 participating hospitals: selection of women with GDM who have unmet post prandial glycemic targets between 14 and 37 (+6 days) weeks of amenorrhea after at least 7 days of dietary and lifestyle measures. They may be treated with basal insulin to control pre prandial glucose values.
Explanation of protocol, with signature of consent in case of acceptation.
Randomization
. Experimental group: The women will receive acarbose with a progressive increase of dose according to post prandial glucose values and digestive tolerance, with a maximal dose of 3 x 100 mg / day. The progressive titration of acarbose reduces gastro-intestinal side effects.
Patients who have not reached the glycemic targets at this highest tolerated dose for at least one meal will receive instead prandial insulin therapy for each meal, whereas acarbose will be stopped. Failure to reach post-prandial target will be defined as 3 or more post-prandial glycaemic values ≥ 1.20 g/L for a given meal in a week (3 values out of 7) after the two weeks of dose adjustment.
· Control group: The women will receive prandial insulin according to usual practice (routine care according to French recommendations): before each meal, with dose titration according to post prandial values.
Basal insulin may be necessary in both arms to control pre-prandial glucose values.
At delivery:
- Maternal blood samples : 14 ml of blood will be collected at the same time as the sample routinely collected just before delivery for irregular agglutinin test measurement, when the women are perfused.
- Cord fluid : 7 ml will be collected at the same as cord fluid pH is routinely measured just after delivery. There will be 5 aliquots to prepare.
The aliquots previously labelled and stowed in the specific boxes for the study will be stored locally and will be transported to the "Centre de Ressources Biologiques"(CRB) of the Jean Verdier Hospital.
Routine monitoring of the women with GDM in both arms, up to delivery. No use of other oral hypoglycemic agents during pregnancy.
Last consultation three months after delivery.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gestational Diabetes Mellitus in Pregnancy
Keywords
Diabetes, Pregnancy, Gestational, Acarbose
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
341 (Actual)
8. Arms, Groups, and Interventions
Arm Title
acarbose
Arm Type
Experimental
Arm Description
The women will receive acarbose with a progressive increase of dose according to post prandial glucose values and digestive tolerance, with a maximal dose of 3 x 100 mg /day
Arm Title
prandial insulin
Arm Type
Active Comparator
Arm Description
The women will receive prandial insulin according to usual practice (routine care according to French recommendations): before each meal, with dose titration according to post prandial values.
Intervention Type
Drug
Intervention Name(s)
Acarbose
Other Intervention Name(s)
Glucor 50 mg
Intervention Description
Women will receive acarbose at an initial dose of 50 mg once daily in the beginning of the meal for which the postprandial glucose value is the highest, with progressive increase every 2 days or more: adding a pill before another meal, and then increasing dose of acarbose to 100 mg if post-prandial glucose goals are not obtained, with a maximal dose of 3 x 100 mg / day.
Intervention Type
Drug
Intervention Name(s)
Prandial insulin
Other Intervention Name(s)
Rapid acting insulin analog
Intervention Description
Women will receive prandial fast-acting insulin according to usual practice (routine care according to French recommendations), i.e. one injection before each meal usually.
Primary Outcome Measure Information:
Title
Composite endpoint: birth weight ≥ 90th percentile for gestational age (large for gestational age: LGA) and/or neonatal hypoglycemia and/or shoulder dystocia and/or birth injury.
Description
LGA defined as birth weight greater than the 90th percentile for a standard French population
Neonatal hypoglycemia defined as at least a blood glucose value less than a 2.0 mmol/l during the two first days of life;
Shoulder dystocia, defined as vaginal cephalic delivery that requires additional obstetric manoeuvres to deliver the fetus after the head has delivered and gentle traction has failed. We will only consider rotational maneuvers such as Rubin II or Woods corkscrew or Jaquemier maneuvers
Birth injury defined as plexus injury or clavicle fracture.
Time Frame
At delivery
Secondary Outcome Measure Information:
Title
GLUCOSE CONTROL: Capillary glucose levels
Description
The women will be asked to perform 6 measures a day. Capillary glucose values will be retrieved from the glucose meter, and if not available, from the woman's diary.
Time Frame
From two weeks after inclusion : 14 and 37 (+6 days) weeks of amenorrhea to delivery
Title
GLUCOSE CONTROL: HbA1c
Description
Centralized measurement
Time Frame
At delivery
Title
GLUCOSE CONTROL: Need for and dose/day of basal and prandial insulin in both arms
Description
This information will be retrieved from the glucose meter, and if not available, from the woman's diary.
Time Frame
At delivery
Title
Neonatal complications : Birth weight and height,
Description
Birth weight ≥ 4000g Birth weight ≥ 4500g
Time Frame
At delivery
Title
Neonatal complications : Small for gestational age infant
Description
SGA: birth weight lower than the 10th percentile for a standard French population
Time Frame
At delivery
Title
Maternal complications : Preeclampsia
Description
Preeclampsia (blood pressure ≥ 140/90 mmHg on two measurements four hours apart and proteinuria of at least 300 mg/24 hours or 3+ or more on dipstick testing or proteinuria/creatininuria >30 in a random urine sample).
Time Frame
From two weeks after inclusion to delivery
Title
Maternal complications : Pregnancy-induced hypertension
Description
In women with no known hypertension before pregnancy, blood pressure ≥ 140/90 mmHg on two measurements four hours apart without proteinuria and having needed to begin anti-hypertensive therapy
Time Frame
From two weeks after inclusion : 14 and 37 (+6 days) weeks of amenorrhea to delivery
Title
Neonatal complications : Preterm delivery
Description
Late preterm infant (between 32 and 37 completed weeks' gestation)
Very preterm infant (28-31 completed weeks' gestation)
Extreme preterm infant (less than 28 completed weeks' gestation)
Time Frame
At delivery
Title
Neonatal complications : Low Apgar score
Description
5-min Apgar score < 7
Time Frame
At delivery
Title
Neonatal complications : Neonatal respiratory distress syndrome
Description
based on the clinical course, chest X-ray finding, blood gas and acid-base values
Time Frame
At delivery
Title
Neonatal complications : Intrauterine fetal or neonatal death;
Description
These endpoints will be extracted from the women' charts
Time Frame
From two weeks after inclusion to delivery
Title
Acceptance/satisfaction of two strategies : -Quality of life -Satisfaction questionnaires
Description
Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36)
- use of analogic scales
Time Frame
At delivery
Title
Side effects of drugs : Maternal hypoglycemia
Description
Severe hypoglycemia: requiring assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma/capillary glucose to normal is considered sufficient evidence that the event was induced by a low plasma/capillary glucose concentration.
event during which typical symptoms of hypoglycemia are accompanied by a measured capillary glucose concentration <70 mg/dL (<3.9 mmol/L).
Asymptomatic hypoglycemia: event not accompanied by typical symptoms of hypoglycemia but with a measured capillary glucose concentration <60 mg/dL (<3.3 mmol/L).
Time Frame
during the 7 months of treatment
Title
Gastro-intestinal side effects
Description
The events occuring during the last 14 days of pregnancy or gastro-intestinal side effects leading to treatment withdrawl
Time Frame
from two weeks after inclusion : 14 to 36 weeks of gestation to delivery
Title
Results of oral glucose tolerance test and HbA1c measurement
Description
Test will be performed by the women before follow up visit
Time Frame
3 months after delivery
Title
Infant anthropometrics.
Description
These data will be collected from children's health record
Time Frame
At month 1, month 2 and month 3
Title
Conservation of serum and plasma; cord fluid. The samples may be used for further analyses ancillary studies and which could be beneficial for GDM care based on evolution in scientific knowledge.
Description
The blood samples will be collected at the same time as the sample routinely collected just before delivery for irregular agglutinin test measurement.
Cord fluid will be collected
Time Frame
within 10 years after the end of the study
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
The participants in this study are pregnant women with gestational diabetes mellitus.
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18 years
Singleton pregnancy
GDM diagnosed during pregnancy according to IADPSG criteria
Self-monitoring of blood glucose
After at least 7 days of dietary and lifestyle measures, unreached post-prandial glucose control
14-37 (+ 6 days) amenorrhea weeks at the time of randomization
Signed informed consent
Exclusion Criteria:
Prandial insulin use before randomization during this pregnancy
Use of other oral hypoglycemic agents during this pregnancy
Multiple pregnancy
Known hepatic insufficiency
Long time corticosteroid treatment
Pre-existing diabetes in pregnancy
Overt diabetes diagnosed during pregnancy (IADPSG criteria)
Lack of Social Insurance
Insufficient understanding
Participant in another investigational drug study at inclusion visit
Contraindications of acarbose
Fetal malformation diagnosed by previous fetal ultrasound
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emmanuel COSSON, MD-PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jean Verdier Hospital
City
Bondy
ZIP/Postal Code
93140
Country
France
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
18463376
Citation
Rowan JA, Hague WM, Gao W, Battin MR, Moore MP; MiG Trial Investigators. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med. 2008 May 8;358(19):2003-15. doi: 10.1056/NEJMoa0707193. Erratum In: N Engl J Med. 2008 Jul 3;359(1):106.
Results Reference
background
PubMed Identifier
11036118
Citation
Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med. 2000 Oct 19;343(16):1134-8. doi: 10.1056/NEJM200010193431601.
Results Reference
background
PubMed Identifier
24528229
Citation
Holt RI, Lambert KD. The use of oral hypoglycaemic agents in pregnancy. Diabet Med. 2014 Mar;31(3):282-91. doi: 10.1111/dme.12376.
Results Reference
background
PubMed Identifier
10774102
Citation
Zarate A, Ochoa R, Hernandez M, Basurto L. [Effectiveness of acarbose in the control of glucose tolerance worsening in pregnancy]. Ginecol Obstet Mex. 2000 Jan;68:42-5. Spanish.
Results Reference
background
Citation
Platt J, O'Brien W. Title Acarbose therapy for gestational diabetes: a retrospective cohort study (abstract). Review AJOG 2003;189:S107
Results Reference
background
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Acarbose and Prandial Insulin for the Treatment of Gestational Diabetes Mellitus.
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