E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
autonomous cortisol secretion |
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E.1.1.1 | Medical condition in easily understood language |
autonomous cortisol secretion |
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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 |
Assess improvement in hypertension and/or glucose metabolism in patients with ACS before and after a trial treatment period of 6 months with cortisol lowering drugs. |
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E.2.2 | Secondary objectives of the trial |
- Assess improvement in other metabolic parameters (weight / BMI, bone health, cholesterol profile) in the patient with ACS before and after a trial treatment period of 6 months with cortisol lowering drugs. - Assess the effect of the trial treatment on mental illness and quality of life (assessed by Cushing QoL, a disease-specific quality of life form for Cushing's syndrome, and general quality of life form SF36). -Assess the effect of the trial treatment on bone health (assessed by bone density measurement and bone markers -blood tests that show whether bone degradation is taking place)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Must be at least 18 years of age. • Patients with ACS and one or more metabolic-, bone- and / or psychiatric complications. • The patient is eligible for surgical treatment with adrenalectomy • Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations.
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E.4 | Principal exclusion criteria |
• Patients with fulminant Cushing syndrome, who should be given priority for prompt surgery • The patient is not able to collaborate on the follow-up in the study • Patients living far away from nearest hospital making follow-up at a local hospital difficult. • Pregnant women
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E.5 End points |
E.5.1 | Primary end point(s) |
• Laboratory tests related to the diagnosis of ACS. As cortisol can not be evaluated after short DST during ongoing treatment with Metycor, a reduction in s-cortisol in a basal morning blood sample will be used. We considered that adequate lowering of s-cortisol is achieved if s-cortisol is halved after treatment with Metycor, and / or s-cortisol is below 300 nmol / L in the basal morning test. • Blood pressure: the patient will perform normal standardized blood pressure measurement at the start and end of the study, and 24-hour blood pressure measurement at the corresponding time. Significant reduction is considered as a 10% reduction in systolic and / or diastolic blood pressure, and/or achieving a 5% nocturnal dip during the treatment period. • Glucose metabolism: The patient measures long-term blood sugar, HbA1C, at onset, after 3 months and at the end of the project. At a similar time, the patient will also be equipped with a 14-day tissue glucose monitor that sends tissue glucose values directly to a mobile phone and which can be read with a number of parameters afterwards. Time in range, time below and above range, glucose variability, etc. A 0.5% (5 mmol/mol) reduction in HbA1C, or a 10% increase in TIR is considered as significantly improved glycemic control.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after 3 and 6 months treatment |
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E.5.2 | Secondary end point(s) |
• Weight: Weight, BMI and body composition are measured (body impedance) at inclusion, after 3 and 6 months. Weight reduction of more than 2 kg during the treatment period is considered a significant weight reduction. •Bone metabolism: A baseline bone density measurement will be taken before starting the treatment study. Furthermore, bone markers (blood samples) are taken at the time 0, 3 months and 6 months - to assess bone metabolism. It is categorically assessed whether there is a change in bone markers from degradation to build-up of bone, before compared to after treatment. •Cholesterol profile: (s-cholesterol, LDL, HDL and Triglycerides) is taken at baseline, after 3 and 6 months). A 5% decrease in LDL is considered significant. • Psychiatric symptoms / quality of life: Assessed at baseline, after 3 and 6 months with two questionnaires (general quality of life at SF36, and disease-specific form Cushing QoL). Change in score is assessed individually for each form.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
after 3 and 6 months treatment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | 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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
conventional handling of disease, treatming symptoms |
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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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
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 | |
E.8.9.1 | In the Member State concerned days | |