Timing of Sodium Intake and Nocturnal Sodium Excretion and Blood Pressure in Obese
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 61
- 试验地点
- 1
- 主要终点
- Sleep Systolic Blood Pressure
研究概览
简要总结
Experimental data have shown that timing of sodium intake impacts diurnal patterns of sodium excretion. The purpose of this study is to test the hypothesis that the time of day for salt intake impacts (1) blood pressure rhythms and urinary sodium excretion and (2) circadian timing of factors responsible for blood pressure regulation and cardiometabolic health in obese individuals. These studies will address two aims. The first aim will test the hypothesis that limiting high salt intake prior to sleep increases day-night differences in blood pressure, improves timing of urinary sodium excretion, and improves metabolic risk factors. The second aim will test the hypothesis that limiting high salt intake prior to sleep preferentially improves rhythmicity in peripheral vs. central circadian clock factors linked to renal sodium handling. The proposed hypothesis-driven studies will determine how timing of sodium intake affects diurnal blood pressure and circadian timing of factors responsible for blood pressure control and metabolic health, with the ultimate goal of identifying novel strategies to treat nocturnal hypertension and metabolic disease in obesity.
详细描述
Timing of food intake affects a variety of pathophysiological systems. The Western diet, which is high in salt, also contributes to excess morbidity and mortality related to obesity and hypertension. Nocturnal hypertension frequently occurs in obesity and is recognized as an important consequence of hypertension risk, yet the mechanisms involved in this phenomenon are poorly understood. Experimental data from our group have shown that timing of sodium intake impacts diurnal patterns of sodium excretion. Further, we recently reported that high salt intake causes a shift in expression of circadian control genes in the kidney. Additional studies demonstrate that obese animals have an impaired response to a natriuretic stimulus.
Given the established contribution of high salt intake to obesity-dependent hypertension, particularly, nocturnal hypertension, we hypothesize that the time of day for salt intake impacts (1) blood pressure rhythms and urinary sodium excretion and (2) circadian timing of factors responsible for blood pressure regulation and cardiometabolic health in obese individuals. We will conduct a cross-over feeding study of 55 obese adults.
These studies will address two aims. The first aim will test the hypothesis that limiting high salt intake prior to sleep increases day-night differences in blood pressure, improves timing of urinary sodium excretion, and improves metabolic risk factors. We will monitor 24-hour blood pressure by ambulatory blood pressure monitoring to determine the role of timing of sodium intake on diurnal blood pressure patterns. Day- and night-time sodium excretion will be used to determine whether improvements in blood pressure are mediated by enhanced sodium excretion during the day. We will also assess the effects of timing of sodium intake on lipids, leptin, adiponectin, insulin sensitivity, inflammatory cytokines, and immune cell activation over 24 hours.
The second aim will test the hypothesis that limiting high salt intake prior to sleep preferentially improves rhythmicity in peripheral vs. central circadian clock factors linked to renal sodium handling. Circadian measures of plasma cortisol, dim light melatonin onset, and core body temperature (telemetry) will be used to assess the phase and amplitude of the core circadian clock. Circadian measures of peripheral clock genes in buccal cells and peripheral blood monocytes will be used to determine the phase and amplitude of the peripheral clock.
The proposed hypothesis-driven studies will determine how timing of sodium intake affects diurnal blood pressure and circadian timing of factors responsible for blood pressure control and metabolic health, with the ultimate goal of identifying novel strategies to treat nocturnal hypertension and metabolic disease in obesity
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 25 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •obese (BMI 30-50 kg/m2)
- •25-45 years of age
排除标准
- •evidence of kidney disease (eGFR < 60 ml/min/1.73m2 or abnormal urinalysis)
- •elevated BP (>150/90 mmHg [measured at screening in duplicate after 10min lying recumbent])
- •elevated fasting glucose (>126 g/dL on screening labs)
- •severe anemia (hemoglobin < 8 g/dL for women or < 9 g/dL for men)
- •significant psychiatric illness (as assessed by a validated screening form)
- •past or present drug or alcohol abuse (drug screen)
- •taking 2 or more BP medications or supplements on a regular basis
- •alcohol intake more than 2 drinks/day
- •pregnancy
- •women taking hormone replacement therapy, or post-menopausal women;
- •shift worker
- •sleep disorders (such as sleep apnea assessed by Apnea Link)
- •major chronic disease (e.g., diabetes, lymphocyte disorders)
- •history of smoking or use of tobacco products within the past year
- •use of sleep medications, hypnotics, stimulants, or anti-depressants
研究组 & 干预措施
Late Sodium
Late sodium load: participants will consume a standardized diet providing 2.3 g of sodium per day for 7 days (run-in period), after which they will continue to consume the standardized diet for the next 9 days and in addition will take 2 g of sodium with dinner each day.
干预措施: Oral sodium supplementation (Other)
Early Sodium
Early sodium load: participants will consume a standardized diet providing 2.3 g of sodium per day for 7 days (run-in period), after which they will continue to consume the standardized diet for 9 days and in addition will take 2 g of sodium in the form of salt tablets with breakfast each day.
干预措施: Oral sodium supplementation (Other)
结局指标
主要结局
Sleep Systolic Blood Pressure
时间窗: On the 8th day of consuming the standarized diet plus chicken-based broth
Systolic blood pressure measured during sleep by 24-hour ambulatory blood pressure monitor starting on the 8th day of consuming the standarized diet plus chicken-based broth
次要结局
- 24-hour Urinary Sodium Excretion(On the 9th day of consuming the standarized diet plus chicken-based broth)
- Concentrations of Plasma Melatonin(On the 9th day of consuming the standarized diet plus chicken-based broth)
- Concentrations of Plasma Cortisol(On the 9th day of consuming the standarized diet plus chicken-based broth)
- Concentrations of Plasma Endothelin 1(On the 9th day of consuming the standarized diet plus chicken-based broth)
- Concentrations of Plasma Aldosterone(On the 9th day of consuming the standarized diet plus chicken-based broth)
- Core Body Temperature(On the 8th day of consuming the standardized diet plus chicken-based broth)
- Timing of Plasma Melatonin Increase Under Dim-light Conditions (Dim-light Melatonin Onset)(On the 9th day of consuming the standardized diet plus chicken-based broth)
- Peripheral Blood Monocyte Clock Gene (CLOCK, Bmal1, per1, per2, Rev-erb-alpha, cry1, cry2) Expression(On the 9th day of consuming the standarized diet plus chicken-based broth)
- Concentrations of Plasma Cytokine (TNA-alpha, IL-1, IL-6, IL-12, IL-17, IL-18, IL-23, IL-10, TGB-beta)(On the 9th day of consuming the standarized diet plus chicken-based broth)
- Flow Cytometric Analysis of Circulating Immune Cells (CD3+, CD4+, CD8+, CD14+, CD45+)(On the 9th day of consuming the standarized diet plus chicken-based broth)
研究者
Orlando M. Gutierrez, MD, MMSc
Principal Investigator
University of Alabama at Birmingham