Clinical trial NCT05255900: Effects of Metyrapone in Patients With Hypercortisolism
Official title: Metabolic, Pressor and Neuropsychological Effects of Metyrapone Treatment in Patients With Hypercortisolism
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hypercortisolism
Keywords: cortisol
metyrapone
hypercortisolism
mild hypercortisolism
Lead sponsor: Istituto Auxologico Italiano
Sponsor class: OTHER
Collaborators: name: HRA Pharma
First posted: 2022-02-25
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with hypercortisolism referred to the outpatient clinic who were already on metirapone therapy.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Baseline, 12 weeks, 24 weeks
measure: Proportion of type 2 diabetes mellitus (T2DM) patients with HbA1c ≥7% at baseline who achieved HbA1c <7%
timeFrame: Baseline, 12 weeks, 24 weeks
measure: Proportion of IFG-IGT and T2DM patients with any decrease in dose of antidiabetic drugs
timeFrame: Baseline, 12 weeks, 24 weeks
measure: Proportion of patients without optimal blood pressure (BP) levels at baseline who achieve an optimal BP control
timeFrame: Baseline, 12 weeks, 24 weeks
measure: Proportion of patients with a mean BP reduction of ≥5 mm Hg
timeFrame: Baseline, 12 weeks, 24 weeks
measure: Proportion of hypertensive patients with any decrease in dose of anti-hypertensive drugs
timeFrame: Baseline, 12 weeks, 24 weeks
Secondary outcomes:
measure: Changes of thrombotic risk parameters
timeFrame: Baseline, 12 and 24 weeks
measure: Changes of lipid profile
timeFrame: Baseline, 12 and 24 weeks
measure: Changes of bone turnover markers
timeFrame: Baseline, 12 and 24 weeks
measure: Normalization of cortisol circadian rhythm
timeFrame: baseline, 4 weeks, 12 weeks, 16 weeks, 24 weeks.
measure: Amelioration of psychological symptoms
timeFrame: Baseline, 12 and 24 weeks
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Istituto Auxologico Italiano
Study officials:
affiliation: Istituto Auxologico Italiano IRCCS
name: Chiodini Chiodini, Professor
role: PRINCIPAL_INVESTIGATOR
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