E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Autonomous cortisol secretion in patients with adrenal adenoma |
|
E.1.1.1 | Medical condition in easily understood language |
Autonomous cortisol secretion |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
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 |
Cardiometabolic phenotyping of patients suffering from autonomous cortisol secretion |
|
E.2.2 | Secondary objectives of the trial |
Identifying a disease specific chronobiology profile in patients with altered hypothalamus-pituitary-adrenal (HPA) axis signaling
Investigating the impact of a treatment by metyrapone on cardiometabolic risk factors in patients with autonomous adrenal cortisol secretion |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For patients with autonomous cortisol secretion: i) morning cortisol > 1,8 ug/dl following 1 mg dexamethasone suppression test, without classical clinical features associated with the presence of Cushing’s syndrome. |
|
E.4 | Principal exclusion criteria |
• HbA1c > 8 % and/or treatment with insulin therapy • uncontrolled hypertension (RR > 170/110 mmHg; treatment with no more than 4 antihypertensive drugs) • previous treatment with glucocorticoids within the last 3 months • concomitant treatment with drugs affecting HPA signaling or CYP3A4 metabolism • adrenal tumor with radiological criteria suspicious for malignancy • chronic kidney disease (eGFR < 45 ml/min) • liver disease (ASAT / ALAT > 3 x ULN) • pregnancy or breast feeding • general MR contraindications (claustrophobia, metal devices or other magnetic material in the body which will be hazardous for MR investigation |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Hepatic lipid content (HCL) assessed by 1H magnetic resonance spectroscopy |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Before and after 12 weeks of treatment with metyrapone |
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E.5.2 | Secondary end point(s) |
insulin secretion and sensitivity based on validated indices (HOMA_IR, CLIX) subcutaneous and visceral fat mass, body composition Systolic and diastolic heart function, epicardial and pericardial fat mass ectopic lipid deposition in the skeletal muscle and the myocardium standardized blood pressure measurements parameters of systemic inflammation parameters of the Renin-Angiotensin-Aldosterone system activation hypercoagulability assessment by thrombin generation assays standardized clinical chronotype evaluation by Munich ChronoType Questionnaire and psychological testing body temperature measurements during the day by an actimetry watch analyses of peroxiredoxin oxidation cycles from red blood cells circadian clock transcript changes from peripheral blood mononuclear cells combined untargeted/targeted LC-MS/MS based approaches concentrations of testosterone and adrenal androgen precursors gender specific differences |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Before and after 12 weeks of treatment with metyrapone |
|
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 | 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 | No |
E.8.1.1 | Randomised | No |
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 | No |
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 | No |
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
|
|
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 |