Prospective, Open-Label, Multicenter, International Study of Mifepristone for Symptomatic Treatment of Cushing's Syndrome Caused by Ectopic Adrenal Corticotrophin Hormone (ACTH) Secretion

Study Summary

This study will evaluate whether the drug mifepristone can improve the symptoms of Cushing's syndrome in people with ectopic adrenal corticotrophin hormone (ACTH) secretion. Cushing's syndrome occurs when the adrenal glands produce too much cortisol, a hormone that helps to regulate the body's use of salt and food. Excessive cortisol is usually the result of too much ACTH, the hormone that causes the adrenal glands to make cortisol. The extra ACTH is made either by a tumor in the pituitary gland (called Cushing's disease) or by a tumor somewhere else (called ectopic ACTH secretion). Mifepristone blocks the action of cortisol in the body. The drug has been used safely to treat a few people with Cushing's syndrome and patients with certain kinds of cancer, gynecological diseases and psychiatric disorders. People between 18 and 85 years of age with Cushing's syndrome caused by EXCESS ACTH secretion may be eligible for this study. Candidates are admitted to the hospital for evaluation to confirm Cushing's syndrome and to determine its cause. The evaluation includes blood and urine tests, imaging tests, dexamethasone and corticotropin-releasing hormone tests and inferior petrosal sinus sampling. Patients determined to have Cushing's syndrome due to ECTOPIC ACTH secretion undergo imaging studies (CT, MRI and a nuclear medicine scan) and begin mifepristone therapy. Participants remain in the hospital for the following tests and procedures: * Physical examination, electrocardiogram (EKG) and blood and urine tests * Completion of medical questionnaires * DEXA scan to determine bone mineral density and body composition * Glucose tolerance test * Urine pregnancy test and ultrasound to measure uterine lining thickness (for women) Patients take mifepristone by mouth 3 times a day. The dose is increased every week or so until symptoms improve or the highest dosage allowed is reached. Patients may remain in the hospital for all or part of the dose-finding part of the study. Du

Primary Outcome

Criteria for improvement or normalization of glycemic disorders: A. For diabetic patients (known or diagnosed at pre-inclusion visit) * Decrease in HbA1c \> 0.3% B. For patients with IGT * Normalization of OGTT (2-hour glucose plasma level after 75 g OGTT \< 7.8 mmol/L (140 mg/dL) D. For patients with IFG If impaired fasting glucose is also associated with impaired glucose tolerance during OGTT at pre-inclusion: \- Normalization of OGTT (2-hour glucose plasma level after 75 g OGTT \< 7.8 mmo

Interventions

• DRUG Mifepristone