Myo-inositol for Reduction of Insulin Therapy in Gestational Diabetes Mellitus

Study Overview
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Brief Summary
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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
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Prospective, multicenter, superiority, randomised, double blind study with two arms. In the 17 participating centers (15 in France and 2 in Belgium): selection of women with GDM between 6 to 37 (+6 days) amenorrhea weeks Explanation of protocol, with signature of consent in case of acceptation. 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 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 If applicable, maternal blood samples 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 and cord fluid will be collected at the same as cord fluid pH is routinely measured just after delivery. The aliquots will be transported to the Centre de Ressources Biologiques(CRB) of the Jean Verdier Hospital Events during pregnancy will be collected Last visit three months after delivery. Oral glucose tolerance test, anthropometric measures for women and their child.

Official Title
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Reduction of Insulin Therapy Under Myo-inositol for the Treatment of Gestational Diabetes Mellitus: a Randomized Multicenter and Prospective Trial. MYO-GDM Study

Conditions
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Gestational Diabetes Mellitus

Intervention / Treatment
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* Dietary Supplement: Myo Inositol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Myo Inositol<br>The women will receive 2 caps of Myo Inositol with acid folic a day, until delivery | Dietary Supplement: Myo Inositol<br>* One soft gel capsule containing MI 600 mg and folic acid 200 μg twice a day, until delivery.<br>* Other names: INOFOLIC;|
| Placebo Comparator: Placebo<br>The women will receive 2 caps of placebo (acid folic) a day, until delivery | Other: Placebo<br>* One soft gel capsule of placebo (folic acid 200 μg) twice a day until delivery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of patients requiring insulin therapy during pregnancy | Rate of patients requiring insulin therapy (either basal or prandial). . | At any time during pregnancy up to delivery; assessed up to 29 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - Rate of patients requiring basal insulin therapy during pregnancy- /Rate of patients requiring prandial insulin therapy during pregnancy | This information will be retrieved from the glucose meter, and if not available, from the woman's diary | At any time during pregnancy up to delivery; assessed up to 29 weeks. | 
| - Doses of basal and prandial insulin at delivery- Gestation age when insulin is began - Duration of insulin treatment | Dose of basal insulin (UI) at delivery, if any Dose of prandial insulin (UI) at delivery, if any Gestational age (SA) when basal insulin is started. Gestational age (SA) when prandial insulin is started Duration of basal insulin treatment at delivery, if any Duration of prandial insulin treatment at delivery, if any | At delivery; assessed up to 29 weeks. | 
| Gestational weight gain | Gestational weight gain (Kg) during pregnancy Gestational weight gain (Kg) between inclusion and delivery | At any time during pregnancy up to delivery; assessed up to 29 weeks. | 
| 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. Documented symptomatic hypoglycemia: 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). | from randomization to delivery; assessed up to 29 weeks. | 
| 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. | From the beginning of MI Supplementation to delivery;assessed up to 29 weeks. | 
| Neonatal complications | Birth weight ≥ 4000g; ≥ 4500g ; large and small for gestational age infant Neonatal hypoglycemia defined as at least a blood glucose value lower than 2.0 mmol/l after 2 hours of life during the two first days of life if the newborn is asymptomatic Shoulder dystocia, defined as vaginal cephalic delivery Birth injury defined as plexus injury or clavicle fracture Preterm delivery: Late preterm infant (between 32 and 37 completed amenorrhea weeks) Very preterm infant (28-31 completed amenorrhea weeks) Extreme preterm infant (less than 28 completed amenorrhea weeks) Low Apgar score: 5-min Apgar score < 7• Jaundice, defined as need for neonatal phototherapy • Neonatal respiratory distress syndrome, based on the clinical course, chest X-ray finding, blood gas and acid-base values • Medical need for admission to pediatric or neonatal intensive care unit during the three days following birth • Malformations: the types of malformation will be recorded. | At delivery; assessed up to 29 weeks | 
| Preeclampsia - Pregnancy-induced hypertension - Cesarean section - Maternal inpatient admission during pregnancy | 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/creatinuria >30 in a random urine sample) 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 Maternal inpatient admission during pregnancy after inclusion, not including hospitalization just after delivery | At any time during pregnancy up to delivery; assessed up to 29 weeks. | 
| Side effects | The investigators expect MI not to have any side effect at the dose 1200 mg/day, but possible side effects will be collected. | From the beginning of MI Supplementation to delivery; assessed up to 29 weeks. | 
| Results of oral glucose tolerance test | Test will be performed by the women 3 months post partum | 3 months after delivery | 
| Infant anthropometrics. | These data will be collected from children's health record | At month 1, month 2 and month 3 | 
| Acceptance/satisfaction of 2 strategies: score | Evaluation of the patient's satisfaction about their treatment for GDM at delivery : give a score of 0 to 100: 0 not satisfied; 100 totally satisfied | At delivery; assessed up to 29 weeks. | 
| 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. This biolgical collection is optional | 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 | within 10 years after the end of the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Pregnancy, MYO-INOSITOL, Oral supplementation