Isturisa in Management of Mild Autonomous Cortisol Secretion (MACS)
概览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Change in fasting glucose, HbA1c
概览
简要总结
To characterize the impact of Isturisa on clinical features and comorbidities associated with MACS. The investigators hypothesize that patients treated with Isturisa will exhibit significantly better metabolic indicators (such as fasting glucose, HbA1c, and lipid profile), blood pressure, weight, body composition and bone mineral density than at Baseline. The investigators also assess the effect of Isturisa on quality of life and psychological symptoms in patients with MACS. The investigators hypothesize that treatment with Isturisa will lead to significant improvements in quality-of-life scores and reductions in depression scores compared to Baseline.
详细描述
Mild autonomous cortisol secretion (MACS) is diagnosed in up to 48% of patients with incidentally discovered adrenal tumors or hyperplasia. Based on the finding of adrenal masses in 5% of adults undergoing cross-sectional imaging, the overall prevalence of MACS is about 1-2%. MACS is characterized by autonomous cortisol secretion without the overt symptoms of Cushing syndrome. It is usually associated with low ACTH and DHEAS levels as an indicator of autonomous cortisol secretion. The European Society of Endocrinology-European Network for the Study of Adrenal Tumors (ESE-ENSAT) and the American Association of Clinical Endocrinology (AACE) recommend a cortisol >1.8 μg/dL after 1 mg-DST to define MACS. Several metabolic abnormalities are associated with MACS, including increased cardiovascular disease, mood alteration, hypertension, osteoporosis, hyperglycemia, obesity, weight gain, and lipid abnormalities. Additionally, increased mortality has been reported in MACS patients. Given these complications and increased mortality, there is a need for effective management and treatment options for MACS.
This research aims to evaluate the efficacy and safety of Isturisa in patients with MACS to address the current gap in treatment strategies. By assessing how effectively Isturisa improves cardiometabolic disorders and monitoring its safety profile, the research will seek to provide a clearer understanding of its role as a treatment option in MACS patients who are not a surgical candidate or do not want to pursue surgery. This evaluation is crucial for developing more effective treatment options and improving management strategies for MACS, ultimately contributing to better patient management.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This is an open-label study. No parties are masked
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
- •Adults aged ≥18 years.
- •Diagnosis of mild autonomous cortisol secretion (MACS) defined by:
- •Serum cortisol \>1.8 µg/dL after 1 mg overnight dexamethasone suppression test (DST).
- •Presence of adrenal adenoma confirmed by imaging (CT or MRI).
- •Ability to provide informed consent.
- •Willingness to undergo study procedures including DEXA scan and laboratory assessments.
排除标准
- •Known diagnosis of Cushing's syndrome or overt hypercortisolism.
- •Current or recent (within 3 months) treatment with glucocorticoids or medications affecting cortisol production (e.g., ketoconazole, metyrapone).
- •Severe hepatic impairment or renal failure.
- •Pregnancy or breastfeeding.
- •Known allergy or contraindication to osilodrostat (Isturisa).
- •Participation in another interventional clinical trial within the last 30 days.
- •Any medical or psychiatric condition that, in the investigator's judgment, may interfere with study participation or safety.
研究组 & 干预措施
Isturisa Treatment Arm
Participants diagnosed with Mild Autonomous Cortisol Secretion (MACS) will receive Osilodrostat (Isturisa) as an investigational treatment. The intervention aims to evaluate comorbidities associated with MACS after the initiation of osilodrostat(Isturisa).
干预措施: Osilodrostat (Isturisa) (Drug)
结局指标
主要结局
Change in fasting glucose, HbA1c
时间窗: Baseline, and then every 3 months up to 2 years
glycemic control: fasting glucose, HbA1c
Change in bone mineral density (g/cm²)
时间窗: Baseline, 1 year, and 2 years
Bone mineral density (g/cm²) measured by DEXA scan.
Change in body weight (kg) from baseline during Isturisa treatment
时间窗: Baseline and every 3 months up to 2 years
Change in body weight will be measured at baseline and every follow-up visit (approximately every 3 months) throughout the 2-year treatment period with Isturisa.
Change in lipid profile from baseline during Isturisa treatment
时间窗: Baseline and every 3 months up to 2 years
Serum lipid profile (LDL-C, HDL-C, total cholesterol, triglycerides) will be assessed at baseline and every follow-up visit (approximately every 3 months) during the 2-year treatment period.
Change in body composition (kg)
时间窗: baseline, 1 year and 2 years
Body composition including lean mass and fat mass (kg) measured by DEXA scan.
次要结局
- Change in Quality of Life as assessed by Short Form -36 (SF-36)(Baseline and every 3 months up to 2 years)
- Change in carotid intima-media thickness (CIMT)(Baseline, 1 year, and 2 years)
- Change in adrenal adenoma/hyperplasia size (mm)(Baseline, 1 year, and 2 years)
- Change in Depression Scores as assessed by the Beck Depression Inventory-II(Baseline and every 3 months up to 2 years)