Open-label Study on Treatment of Primary Aldosteronism With Everolimus
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Aldosterone level
研究概览
简要总结
The overall objective is to evaluate everolimus as an aldosterone-lowering drug in the treatment of primary hyperaldosteronism.
详细描述
The purpose of this study is to evaluate everolimus as an aldosterone-lowering drug in treatment of primary aldosteronism.
Primary aldosteronism is defined as a group of disorders in which aldosterone production is inappropriately high and relatively autonomous from regulation by the renin-angiotensin-aldosterone system. It often presents with increased blood pressure and constitutes the most common cause of endocrine hypertension. It is associated with an increased risk of cardiovascular complications, structural and functional renal abnormalities and metabolic syndrome. The goal of primary aldosteronism treatment is to prevent mortality and morbidity associated with hypertension, hypokalemia and direct aldosterone-associated organ damage.
Treatment depends on the underlying cause of primary aldosteronism. In general, patients with aldosterone-producing adenoma and unilateral adrenal hyperplasia are recommended to have adrenalectomy while patients with bilateral adrenal hyperplasia and those not willing to obtain surgery are offered targeted treatment with mineralocorticoid receptor antagonists. However, the use of mineralocorticoid receptor antagonist is related to side effects that include breast tenderness, gynecomastia, sexual dysfunction and menstrual irregularities.
The primary purpose of this proof-of-concept study is to evaluate whether inhibition of adrenocortical mammilian target of rapamycin (mTOR) signalling with everolimus decreases circulating aldosterone levels. The study also aims to determine whether potential changes in aldosterone levels result solely from a direct effect of everolimus on the adrenal gland or could be caused by changes in aldosterone metabolism and/or levels of canonical regulators of adrenal function (ACTH, AngII). The secondary purpose of this study is to test whether everolimus treatment ameliorates hypertension, improves cardiac function and to better understand molecular mechanisms leading to the development of primary aldosteronism.
Participants will receive Everolimus 0.75mg b.i.d. orally for a duration of 14 days. Blood pressure measurements, haemodynamic measurements, blood tests, 24h urine collection and saline Infusion tests will be conducted in order to compare changes in blood pressure, cardiac and kidney function, aldosterone and steroid hormone metabolite levels, activity of the renin-angiotensin-aldosterone system before and after treatment.
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
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
- •Patient with primary aldosteronism
- •Age ≥ 18 years
- •Office blood pressure <160/90 mmHg on antihypertensive therapy
- •For subjects with reproductive potential, willingness to use contraceptive measures adequate to prevent the subject or the subject's partner from becoming pregnant during the study
排除标准
- •Signs of current infection
- •Neutropenia (leukocyte count < 1.5 × 109/L or absolute neutrophil count (ANC) < 0.5 × 109/L)
- •Anemia (hemoglobin < 11 g/dL for males, < 10 g/dL for females)
- •Clinically significant kidney or liver disease (creatinine > 1.5 mg/dL, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2 × ULN, alkaline phosphatase > 2 × ULN, total bilirubin > 1.5 × ULN)
- •Current immunosuppressive treatment or documented immunodeficiency
- •Uncontrolled congestive heart failure
- •Currently pregnant or breastfeeding
研究组 & 干预措施
Intervention
Everolimus 0.75 mg b.i.d. orally for 14 days.
干预措施: Everolimus 0.75 mg (Drug)
结局指标
主要结局
Aldosterone level
时间窗: 28 days
Change in aldosterone level after saline infusion test after the treatment period (Day 15) and after the washout period (Day 28) compared to baseline (Day 0).
次要结局
- Level of plasma renin activity(28 days)
- Steroid hormone metabolites in urine(28 days)
- Level of plasma ACTH(28 days)
- Blood pressure values(28 days)
- Kidney function(28 days)
- Steroid hormones in serum(28 days)
- Level of Potassium(28 days)
- Level of plasma angiotensin II (ATII)(28 days)