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

NCT03380546 | Terminated Phase 3 DMC

• 1 other identifier: P150942
• Study Type: interventional
• Target: 341
• Locations: 1 country
• Sites: 1

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.

Conditions

Gestational Diabetes Mellitus in Pregnancy

Keywords

Diabetes; Pregnancy; Gestational; Acarbose

Outcome Measures

Primary Outcomes (1)

• 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.

  At delivery

Secondary Outcomes (17)

• GLUCOSE CONTROL: Capillary glucose levels

  From two weeks after inclusion : 14 and 37 (+6 days) weeks of amenorrhea to delivery

• GLUCOSE CONTROL: HbA1c

  At delivery

• GLUCOSE CONTROL: Need for and dose/day of basal and prandial insulin in both arms

  At delivery

• Neonatal complications : Birth weight and height,

  At delivery

• Neonatal complications : Small for gestational age infant

  At delivery

Study Arms (2)

acarbose

EXPERIMENTAL

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

Drug: Acarbose

prandial insulin

ACTIVE COMPARATOR

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.

Drug: Prandial insulin

Interventions

Acarbose 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.

Also known as: Glucor 50 mg

acarbose

Prandial insulin 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.

Also known as: Rapid acting insulin analog

prandial insulin

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: The participants in this study are pregnant women with gestational diabetes mellitus.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• (+ 6 days) amenorrhea weeks at the time of randomization
• Signed informed consent

You may not qualify if:

• 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
• Contraindications of acarbose
• Fetal malformation diagnosed by previous fetal ultrasound

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Jean Verdier Hospital

Bondy, 93140, France

Location

Related Publications (5)

• 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.

  PMID: 18463376 BACKGROUND

• 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.

  PMID: 11036118 BACKGROUND

• 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.

  PMID: 24528229 BACKGROUND

• 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.

  PMID: 10774102 BACKGROUND

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

  BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Acarbose; Insulin, Short-Acting

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Trisaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Emmanuel COSSON, MD-PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2017
• First Posted: December 21, 2017
• Study Start: July 4, 2018
• Primary Completion: August 12, 2023
• Study Completion: February 22, 2024
• Last Updated: July 3, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)