Timing of Sodium Intake and Nocturnal Sodium Excretion and Blood Pressure in Obese African Americans

Obesity Clinical Trial

Official title:

Timing of Sodium Intake and Nocturnal Sodium Excretion and Blood Pressure in Obese

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04021355
• Other study ID #: IRB-300003394
• Status: Recruiting
• Phase: N/A
• Start date: July 14, 2020
• Est. completion date: September 30, 2025

Study information

• Verified date: March 2024
• Source: University of Alabama at Birmingham
• Contact: Orlando Gutierrez, MD
• Phone: 205-996-2736
• Email: ogutierrez[@]uabmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 55
• Est. completion date: September 30, 2025
• Est. primary completion date: July 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronobiology Disorders
• Circadian Dysregulation
• Hypertension
• Obesity
• Salt; Excess

Intervention

Other:
• Oral sodium supplementation
Participants will receive dietary sodium supplementation in the form of tablets to be taken either with breakfast or dinner.

Locations

Country	Name	City	State
United States	University of Alabama	Birmingham	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	24-hour blood pressure	Difference in nocturnal blood pressure between study arms	7 days
Primary	Core Body Temperature	Difference in core body temperature between study arms	7 days
Primary	Timing of plasma melatonin increase under dim-light conditions (dim-light melatonin onset)	Difference in the rise of plasma melatonin during the night under dim-light conditions between study arms	8 days
Secondary	24-hour urinary sodium excretion	Difference in day-night urinary sodium excretion between study arms	8 days
Secondary	Buccal cell clock gene expression (CLOCK, Bmal1, per1, per2, Rev-erb-alpha, cry1, cry2)	Difference in buccal cell clock gene expression (CLOCK, Bmal1, per1, per2, Rev-erb-alpha, cry1, cry2) between study arms. Measures of clock gene expression will all be analyzed as fold change from baseline.	8 days
Secondary	Concentrations of plasma melatonin	Difference in plasma melatonin concentrations between study arms	8 days
Secondary	Concentrations of plasma cortisol	Difference in plasma cortisol concentrations between study arms	8 days
Secondary	Peripheral blood monocyte clock gene (CLOCK, Bmal1, per1, per2, Rev-erb-alpha, cry1, cry2) expression	Difference in peripheral blood monocyte clock gene ((CLOCK, Bmal1, per1, per2, Rev-erb-alpha, cry1, cry2)) expression between study arms. Measures of clock gene expression will all be analyzed as fold change from baseline.	8 days
Secondary	Flow cytometric analysis of circulating immune cells (CD3+, CD4+, CD8+, CD14+, CD45+)	Difference in flow cytometric analysis of circulating immune cells (CD3+, CD4+, CD8+, CD14+, CD45+) between study arms. All flow cytometric analyses will be analyzed as percentage of total nucleated cells.	8 days
Secondary	Concentrations of plasma and urine endothelin 1	Difference in plasma and urine endothelin 1 concentrations between study arms	8 days
Secondary	Concentrations of plasma and urine aldosterone	Difference in plasma and urine aldosterone concentrations between study arms	8 days
Secondary	Concentrations of plasma vasopressin	Difference in plasma vasopressin concentrations between study arms	8 days
Secondary	Concentrations of plasma cytokine (TNA-alpha, IL-1, IL-6, IL-12, IL-17, IL-18, IL-23, IL-10, TGB-beta)	Difference in plasma cytokine measures ((TNA-alpha, IL-1, IL-6, IL-12, IL-17, IL-18, IL-23, IL-10, TGB-beta) between study arms. All cytokine measurements will be analyzed as pg/ml.	8 days