Clinical trial NCT03875755: Myo-inositol for Reduction of Insulin Therapy in Gestational Diabetes Mellitus
Official title: Reduction of Insulin Therapy Under Myo-inositol for the Treatment of Gestational Diabetes Mellitus: a Randomized Multicenter and Prospective Trial. MYO-GDM Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Gestational Diabetes Mellitus
Keywords: Diabetes
Pregnancy
MYO-INOSITOL
Oral supplementation
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2019-03-15
Enrollment: 1080
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Gestational diabetes mellitus (GDM) is defined as hyperglycemia first-diagnosed during pregnancy. Glycemic control reduces GDM-related complications. With the new diagnostic criteria of GDM, up to 25% of pregnant women have GDM, whereas it was previously 6-10% in France. Therefore caring for women with 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.

MYO-INOSITOL (MI) is an oral dietary supplement, which reduces insulin resistance. Women with GDM are deficient in MI. MI supplementation safely prevents GDM by 65 to 87% in high-risk women. A pilot study has shown a 75% reduction of the need for insulin during GDM not controlled by diet.

The coordinator investigator propose here, for the first time, a randomized controlled study evaluating MI versus placebo in women with newly diagnosed GDM.

Detailed description: Prospective, multicenter, superiority, randomised, double blind study with two arms.

1. In the 23 participating centers selection of women with GDM between 6 to 37 (+6 days) amenorrhea weeks
2. Explanation of protocol, with signature of consent in case of acceptation.
3. Randomization

   * Experimental group: The women will receive 2 caps of MI with acid folic a day, until delivery
   * Control group: The women will receive 2 caps of placebo (containing only acid folic) a day, until delivery

   In both arms, the participants will be routinely followed up during pregnancy:
   * diet education,
   * self-monitoring of blood glucose before and after meals
   * and during follow-up insulin therapy if glucose value targets are unmet
4. Routine monitoring of the women with GDM in both arms, up to delivery, without use of other oral hypoglycemic agents during pregnancy.

   At delivery:
   * MI (or placebo) will be stopped
   * Events during pregnancy will be collected
5. Last visit three months after delivery. Oral glucose tolerance test, anthropometric measures for women and their child.

Eligibility criteria: Inclusion Criteria:

* Age ≥18 years
* Singleton pregnancy
* GDM diagnosed during pregnancy according to IADPSG (International Association of the Diabetes and Pregnancy Study Groups) criteria, i.e.

  * fasting plasma glucose between 92 mg/dL (5.1 mmol/L) and 125 mg/dL (6.9 mmol/L)
  * and/or 1-hour plasma glucose value after 75 g oral glucose tolerance test (OGTT) ≥ 180 mg/dL (10.0 mmol/L)
  * and/or 2-hour plasma glucose value between 153 mg/dL (8.5 mmol/L) and 199 mg/dL ((11.0 mmol/L)
* or overt diabetes according to 2-hours post OGTT plasma glucose value ≥ 200 mg/dl
* 6 to 37 (+6 days) amenorrhea weeks at the time of randomization
* Capacity for self-monitoring of blood glucose
* Signed informed consent

Exclusion Criteria:

* Insulin use before randomization during this pregnancy
* Use of other oral hypoglycemic agents during this pregnancy
* Long time corticosteroid treatment
* Pre-existing diabetes before pregnancy
* Overt diabetes diagnosed during pregnancy according to fasting plasma glucose ≥ 126 mg/dL (7 mmol/l)
* Lack of Social Insurance
* Insufficient French understanding and speaking
* Participant in another investigational drug study at inclusion visit
* Fetal malformation diagnosed by previous fetal ultrasound
* Personal history of any bariatric surgery
* Hypersensitivity to any ingredient of dietary supplement formulation

Primary outcomes:
measure: Rate of patients requiring insulin therapy during pregnancy
timeFrame: At any time during pregnancy up to delivery; assessed up to 29 weeks.
Secondary outcomes:
measure: - Rate of patients requiring basal insulin therapy during pregnancy- /Rate of patients requiring prandial insulin therapy during pregnancy
timeFrame: At any time during pregnancy up to delivery; assessed up to 29 weeks.
measure: - Doses of basal and prandial insulin at delivery- Gestation age when insulin is began - Duration of insulin treatment
timeFrame: At delivery; assessed up to 29 weeks.
measure: Gestational weight gain
timeFrame: At any time during pregnancy up to delivery; assessed up to 29 weeks.
measure: Hypoglycemia
timeFrame: from randomization to delivery; assessed up to 29 weeks.
measure: Capillary glucose levels
timeFrame: From the beginning of MI Supplementation to delivery;assessed up to 29 weeks.
measure: Neonatal complications
timeFrame: At delivery; assessed up to 29 weeks
measure: Preeclampsia - Pregnancy-induced hypertension - Cesarean section - Maternal inpatient admission during pregnancy
timeFrame: At any time during pregnancy up to delivery; assessed up to 29 weeks.
measure: Side effects
timeFrame: From the beginning of MI Supplementation to delivery; assessed up to 29 weeks.
measure: Results of oral glucose tolerance test
timeFrame: 3 months after delivery
measure: Infant anthropometrics.
timeFrame: At month 1, month 2 and month 3
measure: Acceptance/satisfaction of 2 strategies: score
timeFrame: At delivery; assessed up to 29 weeks.
Other outcomes:
Locations:
city: Bobigny
country: France
facility: Hôpital Avicenne
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Emmanuel COSSON, MD-PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Croze ML, Soulage CO. Potential role and therapeutic interests of myo-inositol in metabolic diseases. Biochimie. 2013 Oct;95(10):1811-27. doi: 10.1016/j.biochi.2013.05.011. Epub 2013 Jun 10.
citation: Unfer V, Carlomagno G, Dante G, Facchinetti F. Effects of myo-inositol in women with PCOS: a systematic review of randomized controlled trials. Gynecol Endocrinol. 2012 Jul;28(7):509-15. doi: 10.3109/09513590.2011.650660. Epub 2012 Feb 1.
citation: Corrado F, D'Anna R, Di Vieste G, Giordano D, Pintaudi B, Santamaria A, Di Benedetto A. The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes. Diabet Med. 2011 Aug;28(8):972-5. doi: 10.1111/j.1464-5491.2011.03284.x.
citation: D'Anna R, Di Benedetto V, Rizzo P, Raffone E, Interdonato ML, Corrado F, Di Benedetto A. Myo-inositol may prevent gestational diabetes in PCOS women. Gynecol Endocrinol. 2012 Jun;28(6):440-2. doi: 10.3109/09513590.2011.633665. Epub 2011 Nov 28.
citation: Matarrelli B, Vitacolonna E, D'Angelo M, Pavone G, Mattei PA, Liberati M, Celentano C. Effect of dietary myo-inositol supplementation in pregnancy on the incidence of maternal gestational diabetes mellitus and fetal outcomes: a randomized controlled trial. J Matern Fetal Neonatal Med. 2013 Jul;26(10):967-72. doi: 10.3109/14767058.2013.766691. Epub 2013 Mar 1.
citation: D'Anna R, Scilipoti A, Giordano D, Caruso C, Cannata ML, Interdonato ML, Corrado F, Di Benedetto A. myo-Inositol supplementation and onset of gestational diabetes mellitus in pregnant women with a family history of type 2 diabetes: a prospective, randomized, placebo-controlled study. Diabetes Care. 2013 Apr;36(4):854-7. doi: 10.2337/dc12-1371. Epub 2013 Jan 22.
citation: D'Anna R, Di Benedetto A, Scilipoti A, Santamaria A, Interdonato ML, Petrella E, Neri I, Pintaudi B, Corrado F, Facchinetti F. Myo-inositol Supplementation for Prevention of Gestational Diabetes in Obese Pregnant Women: A Randomized Controlled Trial. Obstet Gynecol. 2015 Aug;126(2):310-315. doi: 10.1097/AOG.0000000000000958.
citation: Lubin V, Shojai R, Darmon P, Cosson E. A pilot study of gestational diabetes mellitus not controlled by diet alone: First-line medical treatment with myoinositol may limit the need for insulin. Diabetes Metab. 2016 Jun;42(3):192-5. doi: 10.1016/j.diabet.2016.01.005.