Evaluating Alternative Medical Therapies in Primary Hyperparathyroidism
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 69
- 试验地点
- 1
- 主要终点
- Change in Parathyroid Hormone Levels
研究概览
简要总结
This study will evaluate whether blocking the mineralocorticoid receptor, alone, or in combination with the calcimimetic cinacalcet, can lower parathyroid hormone and calcium levels in primary hyperparathyroidism.
详细描述
To conduct a double-blinded, placebo-controlled, randomized intervention study to investigate whether mineralocorticoid receptor (MR) antagonism, alone or in combination with cinacalcet, is an effective therapy for primary hyperparathyroidism (P-HPTH).
Hypothesis
MR antagonism, as a monotherapy or in combination with a calcimimetic, is a mechanism to lower parathyroid hormone (PTH) in primary hyperparathyroidism (P-HPTH).
Study Design: Sixty subjects with P-HPTH will be enrolled to randomly receive eplerenone (a potassium-sparing diuretic that directly blocks the MR), amiloride (a potassium-sparing diuretic that does not directly block the MR), or placebo for 4 weeks. Thereafter, all subjects will receive cinacalcet therapy (a calcimimetic that lowers PTH) in addition to their randomized intervention for an additional 2 weeks.
Anticipated Results: In this proof-of-concept study, eplerenone therapy will lower PTH, serum calcium, and markers of bone resorption in P-HPTH, when compared to placebo. The PTH response to amiloride will resemble that of placebo, suggesting that the eplerenone mediated reductions in PTH are specific to interactions with the MR. Combination therapy with eplerenone + cinacalcet will result in additive or synergistic reductions in PTH, when compared to placebo + cinacalcet or placebo + amiloride.
Implications: MR antagonism (alone or in combination with cinacalcet) may be a mechanism to lower PTH and calcium in P-HPTH, thereby identifying a new potential option in the limited medical therapies for P-HPTH.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •physician diagnosis of active P-HPTH (Serum calcium > upper limit of reference range and serum PTH > ULRR; or Serum Calcium > ULRR AND serum PTH > 30 pg/mL; or Serum Calcium within 0.2 mg/dL of the ULRR and PTH>ULRR).
- •negative pregnancy test in women aged 18-45
排除标准
- •estimated glomerular filtration rate < 60mL/min/1,73m2
- •serum potassium > 5.0 mmol/L
- •age <18 or >80 years
- •diabetes that is not well controlled (HbA1c>8%)\
- •liver failure
- •heart failure
- •history of myocardial infarction or stroke
- •active use of lithium
- •active chronic inflammatory conditions (such as inflammatory bowel disease, rheumatoid arthritis, sarcoidosis)
- •initiation within 3 months of bisphosphonates or cinacalcet
- •need for imminent parathyroidectomy (within the next 6-8 weeks) as determined by their endocrinologist or surgeon
- •absolute serum calcium >13.0 mg/dL
- •positive pregnancy test on any of the study visits for women ages 18-45.
研究组 & 干预措施
Eplerenone + Cinacalcet
Patients with primary hyperparathyroidism will receive eplerenone for 4 weeks followed by the addition of cinacalcet for 2 weeks
干预措施: eplerenone (Drug)
Placebo + Cinacalcet
Patients with primary hyperparathyroidism will receive placebo for 4 weeks followed by the addition of cinacalcet for 2 weeks
干预措施: Placebo (Drug)
Placebo + Cinacalcet
Patients with primary hyperparathyroidism will receive placebo for 4 weeks followed by the addition of cinacalcet for 2 weeks
干预措施: Cinacalcet (Drug)
Amiloride + Cinacalcet
Patients with primary hyperparathyroidism will receive amiloride for 4 weeks followed by the addition of cinacalcet for 2 weeks
干预措施: amiloride (Drug)
Amiloride + Cinacalcet
Patients with primary hyperparathyroidism will receive amiloride for 4 weeks followed by the addition of cinacalcet for 2 weeks
干预措施: Cinacalcet (Drug)
Eplerenone + Cinacalcet
Patients with primary hyperparathyroidism will receive eplerenone for 4 weeks followed by the addition of cinacalcet for 2 weeks
干预措施: Cinacalcet (Drug)
结局指标
主要结局
Change in Parathyroid Hormone Levels
时间窗: Change in circulating PTH levels before and after 4 weeks of double-blinded monotherapy intervention when compared to placebo (PTH at 4 weeks minus PTH at baseline)
Change in circulating PTH levels before and after 4 weeks of double-blinded intervention when compared to placebo
次要结局
- Change in Calcium Levels(Change in serum calcium levels before and after 4 weeks of double-blinded monotherapy intervention when compared to placebo (calcium at 4 weeks minus calcium at baseline))
研究者
Anand Vaidya
Assistant Professor of Medicine, Harvard Medical School
Brigham and Women's Hospital