Antenatal Myo-inositol Supplementation in Pre-existing Diabetes (AMulet)

National University Health System (NUHS)

Status: Enrolling

Conditions: Perinatal and Neonatal Outcomes in Pregnancies With Type 2 Diabetes Mellitus (T2DM)

Treatments: Dietary Supplement: Folic acid supplement; Dietary Supplement: Myo-inositol and folic acid supplement

Study type: Interventional

Funder types: Other

Identifiers

NCT07241221

2024-4610

Details and patient eligibility

About

This feasibility pilot study aims to gather data that can guide the design of a larger, more comprehensive trial to establish the effects of myo-inositol supplementation on supporting healthy outcomes in pregnancies complicated by Type 2 Diabetes Mellitus (T2DM). It seeks to assess myo-inositol's potential to support fetal and neonatal health, and optimise maternity outcomes as a complementary approach and adjuvant to existing diabetes mellitus therapies, as well as investigate the underlying biological mechanisms.

Full description

The "Antenatal Myo-inositol supplementation in pre-existing diabetes to promote normal neonatal outcomes (AMulet)" pilot study aims to inform the design of a future double-blind randomised controlled trial which can assess the benefits of myo-inositol supplementation in pregnant women with T2DM. Despite provision of the international standard of care, pregnancies complicated by diabetes remain at high risk of adverse perinatal and neonatal outcomes. Offspring exposed to maternal diabetes in-utero also face increased risks of obesity and cardiometabolic diseases later in life. Myo-inositol supplementation has been trialled in pregnancy for the prevention and treatment of gestational diabetes, as well as in non-pregnant adults with T2DM, where improvements in glycaemic regulation and reduced insulin resistance have been observed with supplementation. However, myo-inositol supplementation has not yet been studied in pregnancies with T2DM. The primary aim of the AMulet trial would be to assess whether myo-inositol supplementation in pregnancies with T2DM can support normal fetal size and neonatal wellbeing. The present AMulet pilot study will assess the feasibility and acceptability of conducting such a trial and, additionally, seek to investigate the biological mechanisms through which myo-inositol may influence maternal and offspring health outcomes.

This pilot will recruit 182 pregnant women with T2DM between 12-16 weeks' gestation into a double-blind placebo-controlled randomized study. All participants will be randomly assigned to either an intervention group (receiving supplementation of myo-inositol with folic acid) or a control group (receiving supplementation with folic acid only). Supplementation will be in the form of similar looking capsules to be taken twice daily from recruitment until delivery.

Data and samples will be collected longitudinally across three study visits during pregnancy that will be arranged to coincide with routine antenatal clinic visits where possible, and a fourth visit soon after delivery. Additionally, there will be two re-supply visits and a post-delivery videoconference call. Other study data comprising antenatal, peripartum, fetal and neonatal outcomes will be extracted from medical records during pregnancy and post-delivery to assess the primary and secondary outcomes.

The binary composite primary outcome of normal fetal/neonatal size and wellbeing will be assessed by analyses on an intention-to-treat basis. Secondary outcomes, comprising maternity and other infant outcomes, will be assessed and quantified in terms of relative risk or mean differences between study groups. Adverse events, participant feedback as well as mechanistic understanding will be obtained.

This structured approach will inform the design of a future RCT by gathering data on feasibility and acceptability, identifying potential issues in protocols and data collection tools, and facilitating sample size calculations for the main trial which will aim to support the optimization of maternal and offspring health outcomes in pregnancies complicated by pre-existing T2DM.

Enrollment: 182 estimated patients

Sex: Female

Ages: 21 to 45 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Pregnant women aged 21 years to 45 years old at the time of recruitment
• Ongoing, viable, singleton intrauterine pregnancy
• Between 12+0 days-16+6 days weeks' gestation at recruitment
• T2DM diagnosed by a documented 75g Oral Glucose Tolerance Test (OGTT) showing a fasting glucose of >7 mmol/L or 2h glucose >11.1 mmol/L, or an HbA1C >6.5%, either prior to pregnancy or during the first 16 weeks of the index pregnancy
• Intend to receive antenatal care and give birth at NUH
• Willing to provide written, informed consent
• Able to swallow capsules and comply with trial procedures

Exclusion Criteria

• Known or suspected fetal aneuploidy or genetic/structural anomaly
• Severe allergy to food items requiring carriage of an Epipen at all times

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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182 participants in 2 patient groups

Intervention (myo-inositol and folic acid supplement)

Experimental group

Description:

Participants in the intervention arm will receive a total of 4 g/day of myo-inositol and 300 mcg/day of folic acid, divided into two daily doses.

Treatment:

Dietary Supplement: Myo-inositol and folic acid supplement

Control (folic acid supplement)

Active Comparator group

Description:

Participants in the control arm will receive a total of 300 mcg/day of folic acid, divided into two daily doses.

Treatment:

Dietary Supplement: Folic acid supplement