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| Name | Class |
|---|---|
| HRA Pharma | INDUSTRY |
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The aims of the present study are to evaluate in patients with mild hypercortisolism the effect of metyrapone treatment on glycometabolic control, blood pressure, thrombotic risk parameters, lipid profile, bone turnover markers, mental health and cortisol circadian rhythm.
This open prospective observational study will include patients with mild hypercortisolism of both adrenal and pituitary origin not candidate for surgery. Patients taking metyrapone since less than a week will be followed up for 24 weeks. During this period of time, patients will be re-evaluated as far as blood pressure control, glycometabolic control, thrombotic risk parameters, lipid profile, bone turnover markers and cortisol circadian rhythm is concerned.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| metyrapone treatment | hypercortisolemic patients taking metyrapone since less than a week (usually 250 mg/day, maximum dose 6000 mg/day) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metyrapone Capsules | Drug | Exposure to 24 weeks of treatment with metyrapone |
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of patients with a mean systolic BP reduction of ≥5 mm Hg | BP levels will be measured with arterial blood pressure monitoring (ABPM) | Baseline, 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in glycometabolic control | i) the proportion of patients without type 2 diabetes achieving normalization of FG (<100 mg/dL) and/or the reduction of 2-hour glucose levels below 140 mg/dL after OGTT; ii) the proportion of patients with type 2 diabetes achieving HbA1c <7% among those with baseline HbA1c ≥7%; | 12 and 24 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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Patients with hypercortisolism referred to the outpatient clinic who were already on metirapone therapy.
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| Name | Affiliation | Role |
|---|---|---|
| Chiodini Chiodini, Professor | Istituto Auxologico Italiano IRCCS | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Istituto Auxologico Italiano | Milan | 20149 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29754638 | Background | Zavatta G, Di Dalmazi G. Recent Advances on Subclinical Hypercortisolism. Endocrinol Metab Clin North Am. 2018 Jun;47(2):375-383. doi: 10.1016/j.ecl.2018.01.003. Epub 2018 Apr 9. | |
| 27212038 | Background | Chiodini I, Morelli V. Subclinical Hypercortisolism: How to Deal with It? Front Horm Res. 2016;46:28-38. doi: 10.1159/000443862. Epub 2016 May 17. |
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| ID | Term |
|---|---|
| D003480 | Cushing Syndrome |
| ID | Term |
|---|---|
| D000308 | Adrenocortical Hyperfunction |
| D000307 | Adrenal Gland Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D008797 | Metyrapone |
| ID | Term |
|---|---|
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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Blood samples
| Normalization of cortisol circadian rhythm |
The cortisol circadian rhythm will be assessed by salivary cortisol levels determination (at 8 AM, 12 AM, 4 PM, 8 PM and 11 PM). |
| baseline, 12 weeks, 24 weeks. |
| Changes of thrombotic risk parameters | The thrombotic risk profile will be evaluated by measuring C-Protein, S-Protein, coagulation factor VIII and anti-thrombin III levels | Baseline, 12 and 24 weeks |
| Changes of lipid profile | The lipid profile modifications will be evaluated by measuring total cholesterol, low-density lipoprotein, high-density lipoprotein and triglycerides | Baseline, 12 and 24 weeks |
| Changes of bone turnover markers | The bone turnover changes will be assessed by measuring calcium, phosphorous, osteocalcin (OC), carboxy-terminal cross-linked telopeptide of type I collagen (CTX) and 24-h urinary calcium/creatinine ratio | Baseline, 12 and 24 weeks |
| Amelioration of psychological symptoms | Psychological symptoms wil be evaluated with Beck Depression Inventory-II (BDI-II), a 21-item self-administered inventory designed to measure the intensity of depressive symptoms (Beck, Steer, & Brown, 1996). Scores ranging between 0 and 13 are indicative of minimal depression; scores that fall between 14 and 19 are considered to reflect a mild level of depression; scores of 20 to 28 are considered moderate; and a score ranging from 29 to 63 is labeled severe. | Baseline, 12 and 24 weeks |
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