A Phase II, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Metyrapone in Subjects Diagnosed With Mild Autonomous Cortisol Secretion (MACS)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- Mayo Clinic
- 入组人数
- 90
- 主要终点
- Glucocorticoid to androgen ratio
研究概览
简要总结
single-center, randomized, double-blind, placebo-controlled Phase 2 study to evaluate safety and efficacy of overnight metyrapone in patients with MACS.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provide written informed consent.
- •Stated willingness to comply with all study procedures and availability for the duration of the study.
- •Age ≥ 18 years
- •Diagnosed with MACS i. at least 2 abnormal post-dexamethasone cortisol results1 mg post-dexamethasone cortisol >1.8 mcg/dL or ii. 8 mg post-dexamethasone cortisol >1 mcg/dL b. Historical dexamethasone suppression test results can be used if performed within 24 months prior to enrollment.
- •Adrenal imaging phenotype consistent with benign disease (adrenal adenoma/s, macronodular or micronodular adrenal hyperplasia)
- •At least one of the following comorbidities:
- •obesity (BMI>30 kg/m2)
- •dysglycemia
- •dyslipidemia
- •hypertension
- •osteoporosis
- •fragility fractures
- •Ability to take oral medication and be willing to adhere to the study intervention regimen.
- •For persons of childbearing potential: : agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of ≤ 5% per year during the treatment period and for 1 month after the last dose of study treatment.
- •Stable timing for bedtime for at least one week prior to on-site study visits.
- •History of difficulty providing blood via standard blood draw methods
排除标准
- •Planned alternative therapy for MACS within 12 months after joining the study.
- •Current use of oral exogenous glucocorticoid therapy
- •Current use of opioid therapy >20 MME/day
- •Planned use of oral exogenous glucocorticoid therapy
- •Planned use of opioid therapy >20 MME/day
- •Use of injectable glucocorticoid within 6 weeks prior to Day 1
- •Investigator's judgement based on history/physical examination that a comorbidity or concomitant medication may impact the hypothalamic-pituitary-adrenal axis or steroid metabolome
- •Uncontrolled intercurrent illness including, but not limited to:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnancy or lactation
- •Known allergic reactions to metyrapone
- •Suspected false positive post-dexamethasone cortisol results due to increased metabolism, poor absorption, or noncompliance with dexamethasone
- •Treatment with another investigational drug or other intervention within lower than specific therapy washout period
研究组 & 干预措施
Placebo
Subjects in the placebo arm will receive a placebo in lieu of study drug
干预措施: Placebo (Drug)
Metyrapone
Subjects in the Metyrapone arm will receive the study drug
干预措施: Metyrapone 250 mg Oral Tablets (Drug)
结局指标
主要结局
Glucocorticoid to androgen ratio
时间窗: 3 and 6 months
Glucocorticoid to androgen ratio will be calculated based on total glucocorticoids and total androgens measured through 25-steroid urine profiling.
Delta salivary cortisone
时间窗: 3 and 6 months
Waking salivary cortisone and bedtime salivary cortisone will be assessed, and delta calculated.
次要结局
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0(0-6 months)
- Change in body mass index (BMI)(3 and 6 months)
- Improvement in hyperglycemia(3 and 6 months)
- Quality of life as assessed by SF36 form(3 and 6 months)
- Adrenal insufficiency symptoms as assessed by the AddiQoL Survey(Baseline, 1 week post dose titration, 3 and 6 months)
- Adrenal insufficiency as assessed through morning ACTH and cortisol measurements.(baseline, 3, 6 months)
- Improvement in hypertension(3 and 6 months)