Impact of Metyrapone on Heart Health in Patients with Adrenal Issues

"Effect of Metyrapone on Cardiovascular Risk Factors in Patients With Adrenal Incidentalomas and Subclinical/Mild Cushing's Syndrome

This study is testing if Metyrapone can improve heart health and lower blood pressure in people with adrenal problems like incidentalomas and subclinical Cushing's syndrome.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna (Academic / other)
• Locations: 3 sites (Bologna and 2 other locations)
• Trial ID: NCT06801249 on ClinicalTrials.gov

What this trial studies

This interventional study evaluates the effects of Metyrapone on cardiovascular risk factors in patients with bilateral adrenal incidentalomas and subclinical Cushing's syndrome. It involves a controlled, randomized, open-label design across three phases: a run-in phase with standardized antihypertensive therapy, followed by randomization and an interventional phase. Patients will undergo regular monitoring of blood pressure and cardiovascular health indicators throughout the study. The aim is to assess how Metyrapone influences blood pressure and other cardiovascular metrics in this specific patient population.

Who should consider this trial

Good fit: Ideal candidates include individuals with bilateral adrenal nodules and subclinical Cushing's syndrome who are experiencing hypertension and cannot undergo surgery.

Not a fit: Patients without adrenal incidentalomas or those who do not have hypertension may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved management of cardiovascular risks in patients with adrenal incidentalomas and Cushing's syndrome.

How similar studies have performed: Other studies have shown promising results with similar interventions in managing cardiovascular risks associated with hormonal disorders.

Eligibility criteria

Inclusion Criteria:

Inclusion criteria - run-in (phase 1)

* Unilateral or bilateral adrenal nodules with benign features associated with thickening of the adrenal arms \>5 mm on abdominal CT scan
* SCS (detected 2 times in the 6 months before run-in) defined by the absence of catabolic signs of Cushing's syndrome in association with any of these 3 conditions:

  * Cortisol levels after dexamethasone 1 mg test \>50 nmol/L associated with baseline ACTH \<10 pg/mL
  * Cortisol levels after dexamethasone 1 mg test \>50 nmol/L associated with increased nocturnal (11 pm) salivary cortisol
  * Cortisol levels after dexamethasone 1 mg test \>138 nmol/L
* Hypertension (BP ≥140/90 mmHg and/or ongoing antihypertensive treatment)
* Patients who cannot undergo surgery
* Acquisition of informed consent.

Inclusion criteria - randomization (phase 2)

\- BP \>100/60 mmHg and \<130/85 mmHg on antihypertensive therapy (lowest effective dose) within 6-10 months after enrollment.

Exclusion Criteria:

* Body mass index ≥40 kg/m2
* Pregnant or lactating women; diagnosis of pregnancy will be made by serum β-HCG assay
* Women of childbearing age using contraceptive measures other than barrier contraception. Barrier contraceptive measures are: o Male or female condom with or without spermicide o Cervical cup, diaphragm or sponges with spermicide o Combination of male condom and cervical cup, diaphragm or sponges with spermicide (dual barrier methods)
* Treatment with steroids in the last year before enrollment
* Taking medications known to interfere with Metirapone
* Known or suspected hypersensitivity to the drug or drug class under study
* Patients with serious clinical conditions that, in the opinion of the Investigator, contraindicate the patient's participation in the study
* Patients with primary corticosurrenal insufficiency, impaired adrenal secretion, and severe hypopituitarism
* Patients with impaired liver function
* Patients with untreated hypothyroidism or being treated with drugs that have an action on the hypothalamic-pituitary-adrenal axis
* Patients with hypersensitivity to the active ingredient or any of the excipients listed in section 6.1 of the RCP - Metirapone.

Where this trial is running

Bologna and 2 other locations

• IRCCS Azienda Ospedaliero-Universitaria di Bologna — Bologna, Italy (Recruiting)
• Azienda Ospedaliera Universitaria Federico II — Naples, Italy (Recruiting)
• Azienda Ospedale-Università Padova — Padova, Italy (Recruiting)

Study contacts

• Principal investigator: Guido Di Dalmazi, MD — IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Study coordinator: Guido Di Dalmazi, MD

Conditions Adrenal Incidentalomas; Cushing Syndrome