E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Gestational diabetes mellitus |
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E.1.1.1 | Medical condition in easily understood language |
Diabetes that first presents in pregnancy |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018210 |
E.1.2 | Term | Gestational diabetes mellitus |
E.1.2 | System Organ Class | 100000004868 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess in obese pregnant women at high risk of GDM the efficacy of a) dietary advice, b) metformin treatment plus dietary advice to improve maternal glycaemic control when compared with c) standard care. |
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E.2.2 | Secondary objectives of the trial |
1) To assess feasibility of risk assessment for GDM using the new prediction tool in obese women. 2) To determine the impact of each intervention on a targeted maternal metabolome (Nuclear Magnetic Resonance, NMR). 3) To examine the effect of each intervention on dietary intake.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Female, over 16 years BMI ≥30kg/m2 High risk of GDM as identified by the risk assessment at screening Singleton pregnancy Gestation 21-14+6 weeks’ at the time of screening consent Willing and able to give written informed consent
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E.4 | Principal exclusion criteria |
Women identified as being low risk of GDM Pre-existing diabetes HbA1c ≥6.5mmol/l at screening in early pregnancy Hypertension requiring treatment pre-pregnancy/in pregnancy Thyroid disease Coeliac disease Systemic Lupus Erythematosus Antiphospholipid syndrome (APS) Thalassaemia Current psychosis Taking metformin Taking medications that affect insulin sensitivity Past bariatric surgery Sickle Cell Multiple pregnancy Insufficient understanding of the trial Participation in another IMP trial at the time of screening consent Contraindications to Metformin: • Hypersensitivity to metformin hydrochloride or to any of the excipients. • Diabetic ketoacidosis, diabetic pre-coma • Renal failure or renal dysfunction (creatinine clearance < 60 mL/min) • Acute conditions with the potential to alter renal function such as: - dehydration - severe infection - shock - intravascular administration of iodinated contrast agents • Acute or chronic disease which may cause tissue hypoxia such as: - cardiac or respiratory failure - recent myocardial infarction - shock • Hepatic insufficiency, acute alcohol intoxication, alcoholism • Lactation • Any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis) • Severe renal failure (GFR <30 mL/min)
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E.5 End points |
E.5.1 | Primary end point(s) |
A reduction in mean glucose/24hr of 0.5mmol/l after 8-week treatment, as assessed using continuous glucose monitoring. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary outcome will be evaluated at 22-25 weeks gestation. |
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E.5.2 | Secondary end point(s) |
a) Other glycaemic parameters; mean daytime glucose 0.700-23.00h, mean nocturnal glucose 23.00-0.700h, percentage time in tight glucose control target 3.5- 6.7mmol/L, percentage time in NICE recommended glucose control target 3.5-7.8mmol/L, AUC <6.7mmol/L, AUC <7.8mmol/L, glucose variability measures (glucose SD, glucose CV standard deviation, correlation of coefficient), High Blood glucose index (HBGI), Low Blood glucose index after 8-week treatment and at 32-36 weeks gestation; GDM diagnosis at 24-28 weeks' (IADPSG and NICE criteria). b) metabolome at 14-17 weeks and 24-28 weeks gestation. c) dietary intake at 14-17 weeks, 22-25 weeks, and 32-36 weeks gestation.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
a) Other glycaemic parametersÍž 22-25 weeks gestation and at 32-36 weeks gestationÍž GDM diagnosis at 24-28 weeks' gestation. b) metabolome at 14-17 weeks and 24-28 weeks gestation c) dietary intake at 14-17 weeks, 22-25 weeks, and 32-36 weeks gestation |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
dietary advice or standard antenatal care |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |