Prospective, Open-Label, Multicenter, International Study of Mifepristone for Symptomatic Treatment of Cushing's Syndrome Caused by Ectopic Adrenal Corticotrophin Hormone (ACTH) Secretion
Between 10% and 20% of patients with hypercortisolism (Cushing's Syndrome) have tumoral
ectopic production of adrenocorticotropin hormone (ACTH) that causes cortisol excess. If an
ectopic tumor cannot be found or if surgery cannot be done, the treatment options include
medicines that reduce cortisol production and bilateral adrenalectomy. The available
medications that reduce cortisol production have important adverse effects and are not
effective in some patients and adrenalectomy leads to lifelong requirements for medical
hormone replacement. Thus, additional treatment options would be welcome. This study
evaluates a potential new medication for the treatment of these patients; mifepristone
blocks the effects of cortisol rather than decreasing its production. The purpose of this
study is to see whether this agent can improve diabetes or other symptoms of Cushing's
syndrome in subjects with ectopic ACTH secretion. Another purpose is to evaluate adverse
effects with this drug. Patients with presumed ectopic ACTH secretion and diabetes will
take mifepristone 600 mg daily by mouth, and the effect on diabetes and other symptoms of
Cushing's syndrome will be measured. Subjects will return to the hospital at 2, 3, 6, 9, and
12 months after starting mifepristione for evaluation of diabetes and other symptoms. The
agent will be available for up to 12 months for patients in whom it is effective.
Patients take mifepristone by mouth 3 times a day. Each dose will contain 200 mg. Patients
may remain in the hospital for all or part of the initial safety studies, every two weeks
for eight weeks. During this period blood pressure, glucose tolerance and blood chemistries
are measured and EKG and urinalysis done every two weeks. The mifepristone dose can be
decreased or stopped if there are adverse effects. When the mifepristone dose is stable for
eight weeks, patients will be re-evaluated. Patients then return to the hospital for
evaluations one month later and then every 3 months. Those who do well on the drug may
continue to take it for up to 12 months.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Change in glucose control.
8 weeks at steady dose
Lynnette K Nieman, M.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
United States: Federal Government
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