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 | 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 | 10045228 |
E.1.2 | Term | Type I diabetes mellitus |
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 primary aim of the study is to assess the acute effects of SGLT2 inhibition on parameters reflecting oxygenation and oxygen consumption of the human kidney in persons with type 1 diabetes. |
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E.2.2 | Secondary objectives of the trial |
Exploratory aims are to investigate acute changes in oxygen availability and oxygen access to the kidneys after SGLT2i. This include measures of peripheral blood oxygenation, mitochondrial function and autonomic function. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria healthy controls: • Written informed consent must be provided before participation • Male or female patients >18 years of age with a diagnosis of type 1 diabetes (WHO criteria) • Capable of lying in a MR-scanner for two hours
Inclusion criteria persons with type 1 diabetes: • Written informed consent must be provided before participation • Male or female patients >18 years of age with a diagnosis of type 1 diabetes (WHO criteria) • Urinary albumin creatinine ratio (UACR) ≥30 mg/g in 2 out of 3 consecutive samples (albuminuria) prior to randomization assessed from electronic laboratory database. • Capable of lying in a MR-scanner for two hours
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E.4 | Principal exclusion criteria |
Exclusion criteria for all: • Non-diabetic kidney disease as indicated by medical history and/or laboratory findings • Renal failure (eGFR<15 ml/min/1.73m2), dialysis or kidney transplantation • Treatment with beta-blocking medication • Uncontrolled arrhythmia, 2. or 3. degree AV-block or sick sinus syndrome - assessed from a standard 12-lead electrocardiogram • Pregnancy or breastfeeding (urine HCG is performed on all fertile women) • Systolic blood pressure < 90 or > 200 mmHg • Patients who, in the judgement of the investigator, is incapable of participating • Exclusion criteria for MRI o Claustrophobia o Known heart disease o Known lung disease o Have had surgery the past six weeks o Have foreign bodies of metal in the body (e.g. pacemaker, metal plates, metal screws) • Exclusion criteria for arterial blood gas sampling o Absent pulse o Raynauds syndrome o Buergers Disease (thromboangiitis obliterans) o Inadequate or interrupted circulation o Anticoagulation treatment o Coagulopathies (hypo or hyper coagulable states) o Arterial atherosclerosis o Insufficient collateral perfusion o Partial or full thickness burns over the cannulation site o Synthetic arterial or vascular grafts or infection at the proposed site of cannulation |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary end-point • Renal oxygenation (T2*)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
3 hours from intervention and 6 hours from intervention |
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E.5.2 | Secondary end point(s) |
Exploratory end-points • Renal cortical and medullary perfusion • Renal artery flow • Renal oxygen consumption • Peripheral capillary oxygen saturation (SpO2) • Arterial blood gasses o Arterial blood oxygen partial pressure (PaO2) o Arterial blood oxygen saturation (SaO2) • Peripheral Blood Monocyte mitochondrial function • Circulating inflammatory markers • Baroreflex sensitivity
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
3 hours and 6 hours from intervention: Renal cortical and medullary perfusion, Renal artery flow, Renal oxygen consumption, Peripheral capillary oxygen saturation (SpO2), Arterial blood gasses, Arterial blood oxygen partial pressure (PaO2), Arterial blood oxygen saturation (SaO2)
12 hours from intervention: Peripheral Blood Monocyte mitochondrial function, Circulating inflammatory markers, Baroreflex sensitivity |
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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 | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | Yes |
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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |