Effects of Metyrapone in Patients With Hypercortisolism
- Registration Number
- NCT05255900
- Lead Sponsor
- Istituto Auxologico Italiano
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 20
- Patients with mild Cushing's Syndrome not candidate for surgery
- Current therapy with metyrapone since less than 1 week
- Cortisol levels at 08:00 after 1 mg-overnight dexamethasone suppression test (1mgDST) >1.8 μg/dL
- Confirmed with 2 mg two days dexamethasone suppression test (2mgx2dDST)
- Presence of at least one out of the following conditions: type 2 diabetes mellitus, impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT), arterial hypertension, bone mineral density (BMD) Z-score < -2.0 and/or fragility fracture at any skeletal site
- Stable anti-hypertensive therapies and blood pressure (BP) levels in the month before enrolment
- Stable anti-diabetic therapies and glycometabolic control during the month before enrolment
- Stable body weight during the month before enrolment
- Signs and/or symptoms of overt hypercortisolism (striae rubrae, moon facies, easy bruising, buffalo hump, hypertrichosis)
- Malignant hypertension and/or BP <200/120 mmHg
- Severe hyperglycemia (i.e. FG >350 mg/dL)
- Urinary free cortisol (UFC) higher than 1.5 fold the upper normal range
- Presence of pheochromocytoma or primary hyperaldosteronism
- Possible adrenal metastases or radiological features suggestive for adrenal malignancy (i.e. not homogeneous pattern, necrosis, calcifications, irregular margins, local invasion and high density at computed tomography)
- Congenital adrenal hyperplasia
- Intake of drugs influencing cortisol metabolism and/or secretion
- Women in child-bearing age
- Patients with body mass index (BMI) >35 kg/m2
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description metyrapone treatment Metyrapone Capsules hypercortisolemic patients taking metyrapone since less than a week (usually 250 mg/day, maximum dose 6000 mg/day)
- Primary Outcome Measures
Name Time Method Proportion of IFG-IGT and T2DM patients with any decrease in dose of antidiabetic drugs Baseline, 12 weeks, 24 weeks Proportion of patients with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) at baseline who achieved fasting glucose <100 mg/dL and/or 2-hour glucose <140 mg/dL after a 75 gr-oral glucose tolerance test, respectively Baseline, 12 weeks, 24 weeks Proportion of type 2 diabetes mellitus (T2DM) patients with HbA1c ≥7% at baseline who achieved HbA1c <7% Baseline, 12 weeks, 24 weeks Proportion of patients without optimal blood pressure (BP) levels at baseline who achieve an optimal BP control Baseline, 12 weeks, 24 weeks The optimal targets for BP levels in hypertensive patients are:
* in non-diabetic patients: \<140/90 if ≥65 years, \<130/80 if \<65 years;
* in diabetic patients: \<140/80 mmHg if ≥65 years and \<130/80 if \<65 years BP levels will be measured with arterial blood pressure monitoring (ABPM)Proportion of patients with a mean BP reduction of ≥5 mm Hg Baseline, 12 weeks, 24 weeks BP levels will be measured with arterial blood pressure monitoring (ABPM)
Proportion of hypertensive patients with any decrease in dose of anti-hypertensive drugs Baseline, 12 weeks, 24 weeks
- Secondary Outcome Measures
Name Time Method Changes of thrombotic risk parameters Baseline, 12 and 24 weeks The thrombotic risk profile will be evaluated by measuring C-Protein, S-Protein, coagulation factor VIII and anti-thrombin III levels
Changes of bone turnover markers Baseline, 12 and 24 weeks 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
Changes of lipid profile Baseline, 12 and 24 weeks The lipid profile modifications will be evaluated by measuring total cholesterol, low-density lipoprotein, high-density lipoprotein and triglycerides
Amelioration of psychological symptoms Baseline, 12 and 24 weeks 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.
Normalization of cortisol circadian rhythm baseline, 4 weeks, 12 weeks, 16 weeks, 24 weeks. The cortisol circadian rhythm will be assessed by salivary cortisol levels determination (at 8 AM, 12 AM, 4 PM, 8 PM and 11 PM).
Trial Locations
- Locations (1)
Istituto Auxologico Italiano
🇮🇹Milano, Italy