- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03380546
Acarbose and Prandial Insulin for the Treatment of Gestational Diabetes Mellitus. (ACARB-GDM)
Non-inferiority Between Acarbose and Prandial Insulin for the Treatment of Gestational Diabetes Mellitus: a Randomized Multicenter and Prospective Trial. ACARB-GDM Study.
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Emmanuel COSSON, MD-PhD
- Phone Number: +33 1 48 02 56 80
- Email: emmanuel.cosson@aphp.fr
Study Locations
-
-
-
Bondy, France, 93140
- Jean Verdier Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: acarbose
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
|
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.
Other Names:
|
Active Comparator: prandial insulin
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.
|
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
Time Frame: At delivery
|
LGA defined as birth weight greater than the 90th percentile for a standard French population
|
At delivery
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Infant anthropometrics.
Time Frame: At month 1, month 2 and month 3
|
These data will be collected from children's health record
|
At month 1, month 2 and month 3
|
GLUCOSE CONTROL: Capillary glucose levels
Time Frame: From two weeks after inclusion : 14 and 37 (+6 days) weeks of amenorrhea to delivery
|
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.
|
From two weeks after inclusion : 14 and 37 (+6 days) weeks of amenorrhea to delivery
|
GLUCOSE CONTROL: HbA1c
Time Frame: At delivery
|
Centralized measurement
|
At delivery
|
GLUCOSE CONTROL: Need for and dose/day of basal and prandial insulin in both arms
Time Frame: At delivery
|
This information will be retrieved from the glucose meter, and if not available, from the woman's diary.
|
At delivery
|
Neonatal complications : Birth weight and height,
Time Frame: At delivery
|
Birth weight ≥ 4000g Birth weight ≥ 4500g
|
At delivery
|
Neonatal complications : Small for gestational age infant
Time Frame: At delivery
|
SGA: birth weight lower than the 10th percentile for a standard French population
|
At delivery
|
Maternal complications : Preeclampsia
Time Frame: From two weeks after inclusion to delivery
|
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).
|
From two weeks after inclusion to delivery
|
Maternal complications : Pregnancy-induced hypertension
Time Frame: From two weeks after inclusion : 14 and 37 (+6 days) weeks of amenorrhea to delivery
|
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
|
From two weeks after inclusion : 14 and 37 (+6 days) weeks of amenorrhea to delivery
|
Neonatal complications : Preterm delivery
Time Frame: At delivery
|
|
At delivery
|
Neonatal complications : Low Apgar score
Time Frame: At delivery
|
5-min Apgar score < 7
|
At delivery
|
Neonatal complications : Neonatal respiratory distress syndrome
Time Frame: At delivery
|
based on the clinical course, chest X-ray finding, blood gas and acid-base values
|
At delivery
|
Neonatal complications : Intrauterine fetal or neonatal death;
Time Frame: From two weeks after inclusion to delivery
|
These endpoints will be extracted from the women' charts
|
From two weeks after inclusion to delivery
|
Acceptance/satisfaction of two strategies : -Quality of life -Satisfaction questionnaires
Time Frame: At delivery
|
Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36) - use of analogic scales |
At delivery
|
Side effects of drugs : Maternal hypoglycemia
Time Frame: during the 7 months of treatment
|
|
during the 7 months of treatment
|
Gastro-intestinal side effects
Time Frame: from two weeks after inclusion : 14 to 36 weeks of gestation to delivery
|
The events occuring during the last 14 days of pregnancy or gastro-intestinal side effects leading to treatment withdrawl
|
from two weeks after inclusion : 14 to 36 weeks of gestation to delivery
|
Results of oral glucose tolerance test and HbA1c measurement
Time Frame: 3 months after delivery
|
Test will be performed by the women before follow up visit
|
3 months after delivery
|
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.
Time Frame: within 10 years after the end of the study
|
|
within 10 years after the end of the study
|
Collaborators and Investigators
Investigators
- Principal Investigator: Emmanuel COSSON, MD-PhD, Assistance Publique - Hôpitaux de Paris
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- Platt J, O'Brien W. Title Acarbose therapy for gestational diabetes: a retrospective cohort study (abstract). Review AJOG 2003;189:S107
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
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
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Pregnancy Complications
- Diabetes Mellitus
- Diabetes, Gestational
- Pregnancy in Diabetics
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Glycoside Hydrolase Inhibitors
- Insulin
- Insulin, Globin Zinc
- Acarbose
- Insulin, Short-Acting
Other Study ID Numbers
- P150942
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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.
Clinical Trials on Gestational Diabetes Mellitus in Pregnancy
-
i-Health, Inc.CompletedGestational Diabetes Mellitus in PregnancyGermany
-
The Danish Center for Strategic Research on Type...Odense University HospitalCompletedGestational Diabetes Mellitus in PregnancyDenmark
-
Services Institute of Medical Sciences, PakistanCompletedGestational Diabetes Mellitus in PregnancyPakistan
-
Danone Asia Pacific Holdings Pte, Ltd.Nutricia ResearchTerminatedGestational Diabetes Mellitus in PregnancySingapore
-
Washington University School of MedicineEunice Kennedy Shriver National Institute of Child Health and Human Development... and other collaboratorsCompletedGestational Diabetes | Gestational Diabetes Mellitus in PregnancyUnited States
-
Unity Health TorontoRecruitingGestational Diabetes Mellitus in PregnancyCanada
-
Women's Hospital School Of Medicine Zhejiang UniversityActive, not recruitingGestational Diabetes Mellitus in PregnancyChina
-
Peking Union Medical College HospitalUnknownGestational Diabetes Mellitus in PregnancyChina
-
Gulsum UysalCompletedGestational Diabetes Mellitus in PregnancyTurkey
-
Women's Hospital School Of Medicine Zhejiang UniversityQuzhou Maternal and Child Health Care Hospital; Hangzhou Jianhai Technology...Not yet recruitingGestational Diabetes Mellitus in PregnancyChina
Clinical Trials on Acarbose
-
EMSCompletedType 2 Diabetes MellitusBrazil
-
BayerCompletedDiabetes Mellitus, Type 2Germany
-
BayerCompletedDiabetes Mellitus, Type 2Germany
-
BayerCompleted
-
Guiyang Medical UniversityNot yet recruitingHead and Neck Squamous CarcinomaChina
-
Radboud University Medical CenterCompletedType 2 Diabetes | Endothelial DysfunctionNetherlands
-
The Cleveland ClinicCompleted
-
The University of Texas Health Science Center at...Completed
-
GWT-TUD GmbHTechnische Universität Dresden; University of Regensburg; Diakonissen Krankenhaus...CompletedType 2 Diabetes Mellitus | Subclinical InflammationGermany
-
GWT-TUD GmbHCompleted