Effects of Metyrapone in Patients With Hypercortisolism (CEM)

February 16, 2024 updated by: Istituto Auxologico Italiano

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Estimated)

20

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with hypercortisolism referred to the outpatient clinic who were already on metirapone therapy.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
metyrapone treatment
hypercortisolemic patients taking metyrapone since less than a week (usually 250 mg/day, maximum dose 6000 mg/day)
Drug: Metyrapone Capsules
Exposure to 24 weeks of treatment with metyrapone

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes of thrombotic risk parameters
Time Frame: 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
Baseline, 12 and 24 weeks
Changes of lipid profile
Time Frame: Baseline, 12 and 24 weeks
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
Time Frame: 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
Baseline, 12 and 24 weeks
Normalization of cortisol circadian rhythm
Time Frame: 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).
baseline, 4 weeks, 12 weeks, 16 weeks, 24 weeks.
Amelioration of psychological symptoms
Time Frame: 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.
Baseline, 12 and 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istituto Auxologico Italiano

Collaborators

HRA Pharma

Investigators

  • Principal Investigator: Chiodini Chiodini, Professor, Istituto Auxologico Italiano IRCCS

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 28, 2022

Primary Completion (Estimated)

February 1, 2024

Study Completion (Estimated)

February 1, 2024

Study Registration Dates

First Submitted

February 14, 2022

First Submitted That Met QC Criteria

February 24, 2022

First Posted (Actual)

February 25, 2022

Study Record Updates

Last Update Posted (Actual)

February 20, 2024

Last Update Submitted That Met QC Criteria

February 16, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 05J102

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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