Calcium Channel Blockade in Primary Aldosteronism
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Change in 24-hour Urinary Aldosterone Excretion Rate
研究概览
简要总结
This pilot study explore whether the calcium channel blocker amlodipine can lower aldosterone levels in people with primary aldosteronism.
详细描述
BACKGROUND:
Primary aldosteronism is a common cause of hypertension. The cause of primary aldosteronism can be a unilateral aldosterone-producing adenoma (APA) or bilateral idiopathic hyperaldosteronism (IHA) whereby there is diffuse production of ectopic and non-physiologic aldosterone in the adrenal cortex. IHA likely contributes to the majority of all primary aldosteronism. Whereas surgical cure is the preferred therapy for APA, lifelong mineralocorticoid receptor antagonists (MRAs), such as spironolactone or eplerenone, are used to treat IHA. Treatment is important as patients with primary aldosteronism have an elevated risk of adverse cardiovascular and renal outcomes compared to patients with essential hypertension. It was long thought that curative surgery and lifelong medical therapy were equivalent treatment options, but more recent studies suggest that MRAs may not ameliorate the adverse cardiovascular and renovascular effects of primary aldosteronism to the same extent as surgery. For one, MRAs do not lower aldosterone levels, in fact, aldosterone levels are often increased with MRA therapy. Therefore, for IHA patients with primary aldosteronism in whom surgery is not an option, efforts to improve and optimize medical therapy are important.
Recent evidence in surgically removed adrenal glands from patients with primary aldosteronism and IHA has shown that even though IHA adrenal glands do not harbor adrenal tumors, they do harbor foci of ectopic aldosterone production and these foci are enriched for somatic mutations (gain of function) in CACNA1D, thereby suggesting that calcium channel mutations are predominant in the pathogenesis of IHA. This represents an intriguing target for medical therapy as blockade of this channel could lower intracellular calcium influx and hence decrease aldosterone production. Calcium channel blockade could also represent a more upstream therapy than mineralocorticoid receptor antagonists, which block the action of aldosterone at its receptor rather than lower its production.
This study is a pilot study to test the hypothesis that calcium channel blockade may lower autonomous aldosterone production in primary aldosteronism patients with IHA.
PROTOCOL:
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of primary aldosteronism
- •Idiopathic bilateral hyperaldosteronism subtype based on adrenal venous sampling
- •Primary aldosteronism treated with medical therapy (not surgery)
- •Plasma renin activity <1.0 ng/mL/h
排除标准
- •large or discrete adrenal adenoma on cross-sectional imaging
- •inability to stop calcium channel blocker and transition to alternative medication
- •inability to stop mineralocorticoid receptor antagonist and transition to alternative medication if plasma renin activity > 1.0 ng/mL/h
- •leukopenia
- •thrombocytopenia
- •breastfeeding
研究组 & 干预措施
Amlodipine
Amlodipine (dose 10 mg, once daily)
干预措施: Amlodipine (Drug)
结局指标
主要结局
Change in 24-hour Urinary Aldosterone Excretion Rate
时间窗: Baseline and 2 weeks of amlodipine therapy
Change in 24h urinary aldosterone excretion rate in response to maximal amlodipine therapy
Change in Plasma Aldosterone Concentration
时间窗: Baseline and 2 weeks of amlodipine therapy
Change in plasma aldosterone concentration in response to maximal amlodipine therapy
次要结局
- Acute Change in Plasma Aldosterone Concentration(Baseline plasma aldosterone concentration before amlodipine therapy and 6 hours post-amlodipine dose, compared to baseline plasma aldosterone after 2 weeks of amlodipine therapy and 6 hours post-amlodipine therapy.)
研究者
Anand Vaidya
Associate Professor of Medicine
Brigham and Women's Hospital