2023-507010-27-00
Recruiting
Phase 3
CUSHMAH - Benefit of steroidogenesis inhibitors in Mild Cushing syndrome (Mild Autonomous Cortisol Secretion): a randomized trial in patients with Primary Bilateral Macronodular Adrenocortical Hyperplasia
Assistance Publique Hopitaux De Paris13 sites in 1 country70 target enrollmentStarted: September 1, 2026Last updated:
Overview
- Phase
- Phase 3
- Status
- Recruiting
- Enrollment
- 70
- Locations
- 13
- Primary Endpoint
- At 6 months of treatment number of patients achieving: 1) improvement of blood pressure control and/or 2) improvement of diabetes
Overview
Brief Summary
Demonstrate that cortisol secretion inhibition by medical treatment (metyrapone) in PBMAH patients with MACS lead to improvement of hypertension and diabetes.
Eligibility Criteria
- Ages
- 18 years to 65+ years (18-64 Years, 65+ Years)
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age ≥ 18 years old
- •French speaking
- •Patient with PBMAH as determined by adrenal imaging (CT-scan and/or MRI) showing multiples bilateral supracentrimetric adrenal nodules
- •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
- •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 %)
- •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)
- •For women of childbearing potential (WOCBP), negative bHCG and highly effective contraception
- •For male, an effective method of contraception
- •Signed a written informed consent
- •Affiliated to social security regime or an equivalent system
Exclusion Criteria
- •Patients with a Cushing syndrome from another causes than PBMAH
- •Pregnancy or breastfeeding women
- •Steroidogenesis inhibitor treatment less than 6 weeks before inclusion
- •Pathology that is life-threatening in the short term (1 year)
- •Patients with major psychiatric disorders that may interfere with the smooth running of the study
- •Patients on AME (state medical aid)
- •Participation to another clinical trial on medicinal products for human use
- •Patients with proven primary adrenal insufficiency
- •Under glucocorticoid (systemic or high dose local) treatment
- •Contraindication to steroidogenesis inhibitor
Arms & Interventions
METYRAPONE ESTEVE 250 mg, capsule molle
Test
Intervention: METYRAPONE ESTEVE 250 mg, capsule molle (Drug)
Placebo of metyrapon 250 mg
Placebo
Intervention: Placebo of metyrapon 250 mg (Drug)
Outcomes
Primary Outcomes
At 6 months of treatment number of patients achieving: 1) improvement of blood pressure control and/or 2) improvement of diabetes
At 6 months of treatment number of patients achieving: 1) improvement of blood pressure control and/or 2) improvement of diabetes
Secondary Outcomes
- 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
- 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
- Mean change from baseline to M6 in day-time and night-time Systolic and Diastolic Blood Pressure irrespective of antihypertensive treatment adaptations
- Mean change from baseline to M6 in HbA1c irrespective of antidiabetic treatment adaptations
- 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
- Comparaison of the hormonal and clinical response according to the ARMC5, PDE11A4 and NR3C1 genotypes.
- Collecting data on adverse events
Investigators
Pr Jérôme BERTHERAT (Coordinating investigator)
Scientific
Assistance Publique Hopitaux De Paris
Study Sites (13)
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