E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065542 |
E.1.2 | Term | Prediabetes |
E.1.2 | System Organ Class | 100000004861 |
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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 |
The overall objective is to compare the short-term effectiveness of three glucose-lowering interventions (physical activity, metformin, and dapagliflozin) on glucose variability, body composition, and cardiometabolic risk factors in overweight or obese individuals with pre-diabetes (HbA1c 6.0-6.4%). |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to identify subgroups with different phenotypes who do not respond or respond better than others to lifestyle and pharmacological interventions. Also, to determine how daily exercise bouts and time spent in sedentary and in moderate-to-vigorous physical activity intensities are related to measures of glucose variability, insulin sensitivity and beta cell function.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• HbA1c 6.0-6.4% (42-47 mmol/mol)
• Age 35-70 years
• BMI ≥ 25 kg/m2
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E.4 | Principal exclusion criteria |
• Uncontrolled medical issues including but not limited to cardiovascular pulmonary, rheumatologic, hematologic, oncologic, infectious, gastrointestinal or psychiatric disease; diabetes or other endocrine disease; immunosuppression
• Treatment with hormones which affect glucose metabolism
• Treatment with loop diuretics or thiazolidinediones
• Treatment with beta blockers or peroral steroids
• Bariatric surgery within the past 2 years
• Impaired renal function defined as an estimated GFR<60 ml/min/1.73m2
• Neurogenic bladderdisorders
•Alcohol/drug abuse or in treatment with disulfiram (Antabus) at time of inclusion
• Pegnant or lactating women
•Fertile women not using birth control agents including oral contraceptives, gestagen injection, subdermal implantation hormonal vaginal ring, transdermal application, or intra-uterine devices
•Allergic to one or more of the medications used in the study
•Treatment with peroral steroids
•Concomitant participation in other intervention study
•Unable to understand the informed consent and the study procedures
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E.5 End points |
E.5.1 | Primary end point(s) |
Reduction in mean amplitude of glycaemic excursions (MAGE) from baseline to end-of treatment (measured over 48 hours in the middle of the 6-day measurement periods). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 13 weeks of intervention and 26 weeks after baseline |
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E.5.2 | Secondary end point(s) |
Changes from baseline to end-of-treatment and to 3-months follow-up: •Reduction in HbA1c
•Reduction in intra-day glycaemic variability (CONGA (28));
•Reduction in daily time spent >6.1 mmol/L, >7.0 mmol/L, >7.8 mmol/L, and >11.1 mmol/L;
•Reduction in fasting and 2-hour glucose concentrations during OGTT;
•Improvement in insulin secretion, insulin sensitivity and disposition index;
•Reduction of MAGE and CONGA in subgroups of individuals with different baseline characteristics;
•Reduction in body weight and change in body fat distribution;
•Changes in basal and physical activity energy expenditure and substrate oxidation;
•Changes in time spent sedentary and in moderate-to-vigorous physical activity intensity;
•Reduction in blood pressure and lipids; • Changes in biomarkers of metabolic functions (e.g. metabolites, phospholipids, amino acids, inflammatory markers);
•Number of adverse events and side effects;
•Changes in self-rated health and quality of life;
•Adherence to the different interventions.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 13 weeks of intervention and 26 weeks after baseline |
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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 | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |