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

NCT06801249 | Recruiting Phase 4 DMC

• 1 other identifier: GR-MET-19
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

Brief Summary

Drug interventional, controlled, randomized open-label, parallel-group, multicenter study in patients with bilateral adrenal incidentalomas associated with subclinical Cushing's syndrome

Conditions

Adrenal Incidentalomas; Cushing Syndrome

Outcome Measures

Primary Outcomes (1)

• Change in Number and/or Dosage of Antihypertensive Drugs at 12 Months with Metirapone Treatment, Maintaining Target Blood Pressure Range

  This measure will assess any change in the number or dosage of antihypertensive medications required after 12 months of treatment with Metirapone, while maintaining the target blood pressure range (BP \>100/60 mmHg and \<130/85 mmHg).

  through study completion, an average of 2 months

Secondary Outcomes (2)

• "Concentration of Key Biomarkers in Plasma for Monitoring Efficacy of Metirapone Therapy

  through study completion, an average of 2 months

• "Assessment of Changes in Adrenal Gland Morphology Following Metirapone Therapy

  through study completion, an average of 2 months

Study Arms (2)

Group A

EXPERIMENTAL

Metirapone in addition to standardized antihypertensive therapy, as provided in the normal course of care and in accordance with current European guidelines. Metirapone will be provided in 250-mg capsules, in the form of commercially available packs. In Group A, patients will receive Metirapone at the initial dosage of 250 mg, 1 capsule per day. Dosage may be adjusted according to clinical response and tolerability, up to a maximum of 750 mg (3 capsules per day). The drug should be taken after a meal. The drug should be stored at room temperature. The expected duration of study treatment is 12 months, after which patients will discontinue Metirapone and continue with therapies as per the normal course of care.

Drug: Metarapone

Group B

ACTIVE COMPARATOR

Standardized antihypertensive therapy, as provided in the normal course of care and in accordance with current European guidelines.

Drug: Standardized antihypertensive therapy

Interventions

Metarapone DRUG

Metirapone is an inhibitor of the enzyme 11-β-adrenal hydroxylase, which is deputed to catalyze the conversion of 11-desoxycortisol (11-S) to cortisol and 11-deoxycorticosterone (DOC) to corticosterone.

Group A

Standardized antihypertensive therapy DRUG

Standardized antihypertensive therapy, as provided in the normal course of care and in accordance with current European guidelines.

Group B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• IRCCS Azienda Ospedaliero-Universitaria di Bologna: lead

Study Sites (3)

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Bologna, 40138, Italy

RECRUITING

Azienda Ospedaliera Universitaria Federico II

Napoli, 80131, Italy

RECRUITING

Azienda Ospedale-Università Padova

Padua, 35128, Italy

RECRUITING

MeSH Terms

Conditions

Adrenal incidentaloma; Cushing Syndrome

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases

Study Officials

• Guido Di Dalmazi, MD

  IRCCS Azienda Ospedaliero-Universitaria di Bologna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guido Di Dalmazi, MD

CONTACT

+390512143009; guido.didalmazi@unibo.it

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2024
• First Posted: January 30, 2025
• Study Start: February 23, 2021
• Primary Completion: November 30, 2024
• Study Completion: February 17, 2025
• Last Updated: January 30, 2025

Record last verified: 2024-12

Locations

IT (3)