Clinical trial NCT04021355: Timing of Sodium Intake and Nocturnal Sodium Excretion and Blood Pressure in Obese African Americans
Official title: Timing of Sodium Intake and Nocturnal Sodium Excretion and Blood Pressure in Obese
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Obesity
Hypertension
Circadian Dysregulation
Salt; Excess
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2019-07-16
Enrollment: 55
Sex: ALL
Minimum age (years): 25
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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.

Detailed description: 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

Eligibility criteria: Inclusion Criteria:

* obese (BMI 30-50 kg/m2)
* 25-45 years of age

Exclusion Criteria:

* 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

Primary outcomes:
measure: 24-hour blood pressure
timeFrame: 7 days
measure: Core Body Temperature
timeFrame: 7 days
measure: Timing of plasma melatonin increase under dim-light conditions (dim-light melatonin onset)
timeFrame: 8 days
Secondary outcomes:
measure: 24-hour urinary sodium excretion
timeFrame: 8 days
measure: Buccal cell clock gene expression (CLOCK, Bmal1, per1, per2, Rev-erb-alpha, cry1, cry2)
timeFrame: 8 days
measure: Concentrations of plasma melatonin
timeFrame: 8 days
measure: Concentrations of plasma cortisol
timeFrame: 8 days
measure: Peripheral blood monocyte clock gene (CLOCK, Bmal1, per1, per2, Rev-erb-alpha, cry1, cry2) expression
timeFrame: 8 days
measure: Flow cytometric analysis of circulating immune cells (CD3+, CD4+, CD8+, CD14+, CD45+)
timeFrame: 8 days
measure: Concentrations of plasma and urine endothelin 1
timeFrame: 8 days
measure: Concentrations of plasma and urine aldosterone
timeFrame: 8 days
measure: Concentrations of plasma vasopressin
timeFrame: 8 days
measure: Concentrations of plasma cytokine (TNA-alpha, IL-1, IL-6, IL-12, IL-17, IL-18, IL-23, IL-10, TGB-beta)
timeFrame: 8 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
Study officials:
References: