Effects of Metyrapone in Patients With Hypercortisolism

Hypercortisolism Clinical Trial

— CEM  

Official title:

Metabolic, Pressor and Neuropsychological Effects of Metyrapone Treatment in Patients With Hypercortisolism

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05255900
• Other study ID #: 05J102
• Status: Recruiting
• Start date: April 28, 2022
• Est. completion date: February 2024

Study information

• Verified date: February 2024
• Source: Istituto Auxologico Italiano
• Contact: Chiodini Chiodini, Professor
• Phone: 02619112506
• Email: i.chiodini[@]auxologico.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: February 2024
• Est. primary completion date: February 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Adrenocortical Hyperfunction
• Cushing Syndrome
• Hypercortisolism

Intervention

Drug:
• Metyrapone Capsules
Exposure to 24 weeks of treatment with metyrapone

Locations

Country	Name	City	State
Italy	Istituto Auxologico Italiano	Milano

Sponsors (2)

Lead Sponsor	Collaborator
Istituto Auxologico Italiano	HRA Pharma

Country where clinical trial is conducted

Italy, 

References & Publications (39)

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* Note: There are 39 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Proportion of type 2 diabetes mellitus (T2DM) patients with HbA1c =7% at baseline who achieved HbA1c <7%		Baseline, 12 weeks, 24 weeks
Primary	Proportion of IFG-IGT and T2DM patients with any decrease in dose of antidiabetic drugs		Baseline, 12 weeks, 24 weeks
Primary	Proportion of patients without optimal blood pressure (BP) levels at baseline who achieve an optimal BP control	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)	Baseline, 12 weeks, 24 weeks
Primary	Proportion of patients with a mean BP reduction of =5 mm Hg	BP levels will be measured with arterial blood pressure monitoring (ABPM)	Baseline, 12 weeks, 24 weeks
Primary	Proportion of hypertensive patients with any decrease in dose of anti-hypertensive drugs		Baseline, 12 weeks, 24 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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, 4 weeks, 12 weeks, 16 weeks, 24 weeks.
Secondary	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