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

Gestational Diabetes Mellitus Clinical Trial

— MYO-GDM  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03875755
• Other study ID #: P160940J
• Status: Recruiting
• Phase: N/A
• Start date: March 4, 2020
• Est. completion date: March 4, 2025

Study information

• Verified date: April 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Emmanuel COSSON, MD-PhD
• Phone: 1 48 02 65 80
• Email: emmanuel.cosson[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

1. 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

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

• 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

5. Last visit three months after delivery. Oral glucose tolerance test, anthropometric measures for women and their child.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1080
• Est. completion date: March 4, 2025
• Est. primary completion date: November 4, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes, Gestational
• Gestational Diabetes Mellitus

Intervention

Dietary Supplement:
• Myo Inositol
One soft gel capsule containing MI 600 mg and folic acid 200 µg twice a day, until delivery.

Other:
• Placebo
One soft gel capsule of placebo (folic acid 200 µg) twice a day until delivery.

Locations

Country	Name	City	State
France	Hôpital Avicenne	Bobigny

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (8)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	- 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.
Secondary	- 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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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.
Secondary	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.
Secondary	Results of oral glucose tolerance test	Test will be performed by the women 3 months post partum	3 months after delivery
Secondary	Infant anthropometrics.	These data will be collected from children's health record	At month 1, month 2 and month 3
Secondary	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.
Secondary	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