single-center, randomized, double-blind, placebo-controlled Phase 2 study to evaluate safety and efficacy of overnight metyrapone in patients with MACS.
This study is a double blind, placebo-controlled phase II trial of the safety and efficacy of Metyrapone, in the treatment of MACS. Subjects will be remotely screened and interested qualified subjects will be remotely consented. Subjects will be randomized 2:1 for 6 months of the main study. At 6 months, two options will be available for subjects for months 6-12: open-label arm, observational arm.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
90
Subjects will receive metyrapone beginning at 500 mg and titrating up to 1000 mg
Subjects will receive placebo at 500 mg dose and titrated up to 1000 mg to match interventional arm and prevent unblinding
Glucocorticoid to androgen ratio
Glucocorticoid to androgen ratio will be calculated based on total glucocorticoids and total androgens measured through 25-steroid urine profiling.
Time frame: 3 and 6 months
Delta salivary cortisone
Waking salivary cortisone and bedtime salivary cortisone will be assessed, and delta calculated.
Time frame: 3 and 6 months
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
The investigators will assess adverse events using CTCAE v4.0 at baseline and continuously.
Time frame: 0-6 months
Change in body mass index (BMI)
The investigators will assess for change in the body mass index with metyrapone therapy.
Time frame: 3 and 6 months
Adrenal insufficiency symptoms as assessed by the AddiQoL Survey
The investigators will administer AddiQoL Survey at baseline, 1 week after each dose titration, and at 3 and 6 months.
Time frame: Baseline, 1 week post dose titration, 3 and 6 months
Adrenal insufficiency as assessed through morning ACTH and cortisol measurements.
The investigators will measure ACTH and cortisol in the morning at baseline, 3 and 6 months to assess for biochemical adrenal insufficiency.
Time frame: baseline, 3, 6 months
Improvement in hyperglycemia
The investigators will assess for improvement in hyperglycemia by using a composite assessment defined as: 1) decrease in fasting glucose of Hb1C, or 2) Stable biochemical measurements with a decrease in intensity of hyperglycemia therapy
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Time frame: 3 and 6 months
Improvement in hypertension
The investigators will assess for improvement in hypertension using a composite assessment: 1) improvement in blood pressure measurements while on stable therapy, or 2) stable blood pressure measurements while on a lower intensity hypertension therapy.
Time frame: 3 and 6 months
Quality of life as assessed by SF36 form
The investigators will assess quality of life using SF36 at baseline, 3 and 6 months.
Time frame: 3 and 6 months