METYRAPONE for Primary bilateral macronodular adrenal hyperplasia | Mild autonomous cortisol secretion (Mild Cushing syndrome)

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years old\n- Patient with PBMAH as determined by adrenal imaging (CT-scan and/or MRI) showing multiples bilateral supracentrimetric adrenal nodules\n- Mild autonomous cortisol secretion: plasma cortisol after 1 mg overnight dexamethasone test > 50 nmol/L, 24 h Urinary free cortisol < 1,5 upper limit of Normal\n- Adrenal origin of cortisol excess: morning plasma ACTH < 10 pg/ml or between 10 and 20 pg/ml non responsive to CRH stimulation (stimulation < 50 %)\n- Hypertension (systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg) or treated hypertension and/or diabetes that can be treated with antidiabetic treatments (WHO criteria)\n- For women of childbearing potential (WOCBP), negative bHCG and highly effective contraception\n- For male, an effective method of contraception\n- Signed a written informed consent\n- Affiliated to social security regime or an equivalent system\n- French speaking"}

Exclusion criteria

• {"criterion_text":"- Patients with a Cushing syndrome from another causes than PBMAH\n- Patients with proven primary adrenal insufficiency\n- Under glucocorticoid (systemic or high dose local) treatment\n- Contraindication to steroidogenesis inhibitor\n- Hypersensitivity to the active substance or to one of its excipients\n- Uncontrolled diabetes (HBA1c > 9 %)\n- Loop diuretics and thiazide or thiazide-like diuretic that can cause hypokaliemia\n- Patients at high risk of cardiac rhythm disorders with QT/QTc interval > 470ms (for women) and > 450ms (for men)\n- Drugs with a known risk of QT prolongation as listed in https://crediblemeds.org\n- Pregnancy or breastfeeding women\n- Steroidogenesis inhibitor treatment less than 6 weeks before inclusion\n- Pathology that is life-threatening in the short term (1 year)\n- Patients with major psychiatric disorders that may interfere with the smooth running of the study\n- Patients on AME (state medical aid)\n- Participation to another clinical trial on medicinal products for human use"}

Primary endpoints

• {"endpoint_text":"- At 6 months of treatment number of patients achieving: 1) improvement of blood pressure control and/or 2) improvement of diabetes","definition_or_measurement_approach":"Assessed at 6 months; number of patients achieving improvement in blood pressure control and/or improvement of diabetes. Related measures in secondary endpoints include blood pressure measured by 24h ABPM and diabetes assessed by HbA1c and glucose monitoring at M0, M3 and M6."}

Secondary endpoints

• {"endpoint_text":"- Change of urinary cortisol, salivary cortisol during the circadian rhythm, steroid profile (mass spectrometry analysis) and morning ACTH plasma level at M0, M3 and M6","definition_or_measurement_approach":"Measured at M0, M3 and M6: urinary cortisol, salivary cortisol across circadian rhythm, steroid profile by mass spectrometry, and morning ACTH plasma level."}
• {"endpoint_text":"- Evolution of Body Mass Index, insulin sensitivity as determined by HOMA, glycemia as determined by glucose continuous monitoring, total cholesterol, HDL, LDL, triglyceride at M0, M3 and M6","definition_or_measurement_approach":"Measured at M0, M3 and M6: BMI, HOMA for insulin sensitivity, continuous glucose monitoring for glycaemia, and lipid profile (total cholesterol, HDL, LDL, triglycerides)."}
• {"endpoint_text":"- Mean change from baseline to M6 in day-time and night-time Systolic and Diastolic Blood Pressure irrespective of antihypertensive treatment adaptations","definition_or_measurement_approach":"Mean change from baseline to M6 in daytime and nighttime systolic and diastolic BP; measurement method not specified in primary endpoint but secondary objectives reference 24h ABPM."}
• {"endpoint_text":"- Mean change from baseline to M6 in HbA1c irrespective of antidiabetic treatment adaptations","definition_or_measurement_approach":"Mean change from baseline to M6 in HbA1c."}
• {"endpoint_text":"- Change in the score of the 3 following quality of life and depression questionnaires at M0, M3 and M6: Medical Outcomes Study 36-item short-form health survey (SF-36), the Beck depression inventory (BECK BDI-II) and the QolCushing","definition_or_measurement_approach":"Questionnaire scores (SF-36, Beck BDI-II, QolCushing) assessed at M0, M3 and M6."}
• {"endpoint_text":"- Comparaison of the hormonal and clinical response according to the ARMC5, PDE11A4 and NR3C1 genotypes.","definition_or_measurement_approach":"Comparative analysis of hormonal and clinical responses stratified by genotypes ARMC5, PDE11A4 and NR3C1."}
• {"endpoint_text":"- Collecting data on adverse events","definition_or_measurement_approach":"Safety monitoring: collection of adverse events throughout the study."}

France

Earliest CTIS Part Ii Submission Date

11-02-2026

Latest Decision Or Authorization Date

05-03-2026

Processing Time Days

22

Number Of Sites

13

Number Of Participants

70

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"ESTEVE Pharmaceuticals","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"","full_name":"Ministry of Health - PHRC","duties_or_roles":"Source of monetary support","organisation_type":""}