The Relationship Between Serine Threonine Kinase 39 (STK39) Genotypes, Salt Sensitivity, Thiazide Diuretics-induced Blood Pressure Response
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 124
- 试验地点
- 1
- 主要终点
- Fasting Glucose Change After 7 Days of High Dose (25mg) of HCTZ
研究概览
简要总结
The investigators of this study propose to examine the relationships between STK39 (Serine Threonine Kinase 39) genotypes and responses to salt loading and to thiazide diuretics, hydrochlorothiazide. The investigators hypothesize that STK39 genotypes will be associated with the outcome of both interventions and can contribute to personalized care for hypertension.
详细描述
Although hypertension can be easily diagnosed and there are many medications available to treat hypertension, this condition is poorly managed in many patients and is a leading cause of morbidity and mortality worldwide. Because a newly identified hypertension susceptibility gene, STK39 (Serine Threonine Kinase 39), plays a central role in kidney sodium transport, the investigators propose a pharmacogenetics study to examine the relationships between STK39 genotypes and blood pressure responses to salt loading and to thiazide diuretics, hydrochlorothiazide. In addition, STK39 genotypes may also predict those hypertension patients more likely to develop thiazide-induced hyperglycemia. The investigators hypothesize that STK39 genotypes of those single nucleotide polymorphisms (SNPs) that are associated with baseline systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension status, will be associated with the outcome of both interventions. Therefore these SNPs can act as markers and contribute to personalized care for hypertension by identifying patients most likely to effectively control their blood pressure by adopting salt-reducing diet versus patients most likely to effectively and safely control their blood pressure by taking thiazide diuretics.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Old Order Amish
- •Age 18 to 65
- •Have systolic blood pressure between 120 and 160 and diastolic blood pressure between 80 and 100
排除标准
- •History of myocardial infarction, stroke, congestive heart failure, liver disease
- •Known cause of secondary hypertension
- •Diabetes or Fasting glucose > 100 mg/dL
- •Women who are pregnant, on oral contraceptives, or menstruating
- •Used hydrochlorothiazide (HCTZ) in the last 8 weeks or known allergy to HCTZ
- •Taking non-steroidal anti-inflammatory drugs
- •Estimated glomerular filtration rate < 80 mL/m
- •Intention to alter dietary habit during the study
- •Abuse of alcohol or drug
研究组 & 干预措施
Salt-loading and thiazide diuretic (HCTZ)
Salt loading:2 L of 0.9% NaCl. HCTZ:12.5/ 25 mg of HCTZ for 1 week
干预措施: Salt loading (Procedure)
Salt-loading and thiazide diuretic (HCTZ)
Salt loading:2 L of 0.9% NaCl. HCTZ:12.5/ 25 mg of HCTZ for 1 week
干预措施: Hydrochlorothiazide (HCTZ) (Drug)
结局指标
主要结局
Fasting Glucose Change After 7 Days of High Dose (25mg) of HCTZ
时间窗: Fasting glucose was measured on day 0 and day 8
Values on Day 8 subtracts Day 0.
Blood Pressure Change After 7 Days of Low Dose (12.5 mg) of HCTZ
时间窗: 24-hr Ambulatory blood pressure were measured every hour on day 0 and day 8
Blood pressure change is defined as SBP or DBP average over the 24 hour period, Day 8 subtracts Day 0.
Blood Pressure Change After 7 Days of High Dose (25 mg) of HCTZ
时间窗: 24-hr Ambulatory blood pressure were measured every hour on day 0 and day 8
Blood pressure change is defined as SBP or DBP average over the 24 hour period, Day 8 subtracts Day 0.
Fasting Glucose Change After 7 Days of Low Dose (12.5 mg) of HCTZ
时间窗: Fasting glucose was measured on day 0 and day 8
Values on Day 8 subtracts Day 0.
Blood Pressure Change During Salt Loading
时间窗: Every 15 minutes for 4 hours
Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured every 15 minutes for 4 hours. Blood pressure change is calculated by the trapezoid method. Essentially we use the average of blood pressure at each pair of time points (for example, DBP 30min + DBP 15min)/2 + (DBP 45min + DBP 30min)/2 + ... up to 4 hours.) normalized by baseline SBP/DBP.
次要结局
- Change in Plasma Sodium/Potassium Level Due to Salt-loading(Plasma sodium and potassium measured from blood collected pre and post salt loading)
- Change in Plasma Sodium/Potassium Level During Low Dose of HCTZ(Plasma sodium and potassium measured from blood collected pre and post salt loading)
- Change in Plasma Aldosterone Level Due to Salt-loading(Aldosterone was measured from blood collected pre and post salt loading)
- Change in Plasma Renin Activity Due to Salt-loading(Renin was measured from blood collected pre and post salt loading)
- Change in Plasma Sodium/Potassium Level During High Dose of HCTZ(Plasma sodium and potassium measured from blood collected pre and post salt loading)
研究者
Yen-Pei Christy Chang
Associate Professor
University of Maryland, Baltimore