Evaluation of Metyrapone on Cardiovascular Risk Factors in Patients with Adrenal Incidentalomas and Subclinical/Mild Cushing's Syndrome

The primary objective of this study is to evaluate the **efficacy** of adding Metyrapone to standard antihypertensive treatment in improving blood pressure control in hypertensive patients with subclinical/mild Cushing's syndrome (SCS) and bilateral adrenal tumors. This is clinically relevant as effective blood pressure management in these patients can potentially reduce cardiovascular risk, which is a significant concern in individuals with SCS and adrenal incidentalomas.

Secondary objectives include:

• Identifying **biomarkers** of treatment efficacy and monitoring.
• Evaluating adrenal morphology after treatment with Metyrapone.

The clinical trial involves **patients with adrenal incidentalomas and subclinical/mild Cushing’s syndrome**. The study population includes both male and female participants, aged between 18 and 75 years. Participants are selected based on the presence of monolateral or bilateral adrenal nodules with benign radiological characteristics and an enlarged adrenal limb width greater than 5 mm, as determined by CT scan. The trial targets individuals with subclinical Cushing’s syndrome, characterized by specific cortisol levels after a dexamethasone suppression test and associated with arterial hypertension. Participants are required to have blood pressure readings within a specified range while undergoing antihypertensive therapy. The trial does not include candidates for adrenalectomy. The sponsor has not provided information regarding the total number of participants. The study population is considered vulnerable, and lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **metyrapone** in improving blood pressure control in hypertensive patients with subclinical Cushing's syndrome (SCS) and bilateral adrenal tumors. This is a Phase IV, randomized, double-blind, controlled trial. The study will span approximately 12 months, with an estimated end date of February 20, 2025. Participants will be randomly assigned to receive either metyrapone or a placebo, in addition to their standard antihypertensive treatment. The primary endpoint is the reduction in the number and/or dose of antihypertensive drugs while maintaining blood pressure within a target range.

The trial will commence with a screening visit to assess eligibility based on inclusion criteria, such as age between 18 and 75 years, presence of adrenal nodules with benign characteristics, and specific cortisol levels. Participants will then enter a run-in phase to ensure stability of blood pressure under current antihypertensive therapy. Following successful completion of the run-in phase, eligible participants will be randomized into the treatment phase. Study visits will occur at regular intervals to monitor blood pressure, medication adherence, and any adverse events. The end-of-study visit will evaluate the primary endpoint and overall health status of the participants.

Participant involvement is expected to last for the entire 12-month duration of the trial. However, early termination may occur if participants experience significant adverse effects, fail to adhere to the study protocol, or withdraw consent. The trial is conducted under strict ethical guidelines, ensuring the safety and well-being of all participants throughout the study period.

The clinical trial involves the administration of **Cormeto 250 mg capsule molli**, which contains the active substance **metyrapone**. This experimental medication is presented in a soft capsule form, designed for oral administration. The primary objective of the trial is to evaluate the efficacy of metyrapone in conjunction with standard antihypertensive treatment for improving blood pressure control in patients with subclinical or mild Cushing's syndrome and bilateral adrenal tumors. The maximum daily dose of metyrapone is set at 750 mg, with a total maximum dose of 268.50 grams over the course of the study. The treatment period is limited to a maximum of 12 months. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

In addition to the experimental treatment, participants will continue to receive their standard-of-care antihypertensive therapy. This non-experimental treatment serves as a comparator to assess the added benefit of metyrapone in managing blood pressure. The trial does not include a placebo group, as the focus is on the combination of metyrapone with existing antihypertensive medications. The study protocol emphasizes the importance of maintaining consistent dosing schedules and monitoring participant compliance to accurately assess the treatment's efficacy and safety.

The efficacy of the clinical trial investigating the effect of **metyrapone** on cardiovascular risk factors in patients with adrenal incidentalomas and subclinical/mild Cushing's syndrome will be assessed primarily through the reduction in the number and/or dose of antihypertensive drugs required to maintain blood pressure within a pre-fixed target range. This target range is defined as greater than 100/60 mmHg and less than 130/85 mmHg. The primary endpoint will be evaluated after 12 months of treatment with metyrapone.