E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 1 diabetes mellitus (T1DM) |
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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] - Immune System Diseases [C20] |
MedDRA Classification |
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 investigate the effect of intravenous lactate administration, compared to placebo, on thalamic (regional) CBF during euglycemia and hypoglycemia in patients with T1DM and normal awareness of hypoglycemia. |
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E.2.2 | Secondary objectives of the trial |
To investigate the effect of intravenous lactate administration, compared to placebo, on global CBF during euglycemia and hypoglycemia in patients with T1DM and normal awareness of hypoglycemia.
To assess changes in counterregulatory hormone and symptom responses to hypoglycemia in response to lactate infusion, compared to placebo, in patients with normal awareness of hypoglycemia.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Diabetes duration ≥ 1 year - Age: 18-50 years - Body-Mass Index: 18-30 kg/m2 - HbA1c: 42-75 mmol/mol (6-9%) - Outcome Clarke questionnaire: 0-1 - Blood pressure: <160/90 mmHg
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E.4 | Principal exclusion criteria |
- Inability to provide informed consent - Use medication other than insulin, except for oral contraceptives or stable thyroxin supplementation therapy - Presence of any other medical condition that might interfere with the study protocol, such as brain injuries, epilepsy, a major cardiovascular disease event, or cardiac failure, known liver disease, anxiety disorders or a history of panic attacks. - Microvascular complications of T1DM: o Proliferative retinopathy o Symptomatic diabetic neuropathy (including autonomic neuropathy) o Nephropathy; clinical/overt albuminuria or an estimated glomerular filtration rate <60ml/min/1.73m2 - MR(I) contraindications (pregnancy, severe claustrophobia, metal parts in body)
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E.5 End points |
E.5.1 | Primary end point(s) |
The main study parameter of the study is the change in regional thalamic CBF in response to intravenous lactate infusion compared to placebo, during hypoglycemia. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Change in global CBF in response to intravenous lactate infusion compared to placebo, during hypoglycemia. - Change in plasma levels of counterregulatory hormones in response to hypoglycemia and euglycemia with and without lactate infusion (adrenaline, noradrenaline, growth hormone and cortisol) (pmol/L, nmol/L, mU/L, µmol/L) - Change in glucose infusion rate (GIR): the amount of glucose 20% necessary to maintain plasma glucose at steady state euglycemic or hypoglycemic values (mg/kg/min) with and without lactate infusion - Change in hypoglycemic symptoms scores in response to hypoglycemia with and without lactate infusion
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Global CBF: 15 minute inteval Hormone levels: 1 time per glycemic phase GIR: 5 minute inteval symptoms: beginning and end of glycemic phases |
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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 | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
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 | Yes |
E.8.1.4 | Double blind | No |
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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last visite of last subject |
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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 | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |