Acarbose and Prandial Insulin for the Treatment of Gestational Diabetes Mellitus.

NCT ID: NCT03380546

Last Updated: 2024-07-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 341 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-04
• Study Completion Date: 2024-02-22

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.

1. In the 37 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.

2. Explanation of protocol, with signature of consent in case of acceptation.

3. 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.

4. Routine monitoring of the women with GDM in both arms, up to delivery. No use of other oral hypoglycemic agents during pregnancy.

5. Last consultation three months after delivery.

Conditions

Gestational Diabetes Mellitus in Pregnancy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Acarbose

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

Prandial insulin

Intervention Type: DRUG

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.

Interventions

Acarbose

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

Prandial insulin

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.

Intervention Type: DRUG

Other Intervention Names

Glucor 50 mg; Rapid acting insulin analog

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emmanuel COSSON, MD-PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Jean Verdier Hospital

Bondy, , France

Countries

France

References

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.

Reference Type: BACKGROUND

PMID: 18463376 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11036118 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24528229 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10774102 (View on PubMed)

Platt J, O'Brien W. Title Acarbose therapy for gestational diabetes: a retrospective cohort study (abstract). Review AJOG 2003;189:S107

Reference Type: BACKGROUND

Other Identifiers

P150942

Identifier Type: -

Identifier Source: org_study_id