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

NCT ID: NCT04021355

Last Updated: 2025-12-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-14
• Study Completion Date: 2025-07-31

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

Conditions

Obesity; Hypertension; Circadian Dysregulation; Salt; Excess

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Oral sodium supplementation

Intervention Type: OTHER

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

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.

Group Type: EXPERIMENTAL

Oral sodium supplementation

Intervention Type: OTHER

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

Interventions

Oral sodium supplementation

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

Intervention Type: OTHER

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

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Orlando M. Gutierrez, MD, MMSc

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Alabama

Birmingham, Alabama, United States

Countries

United States

Other Identifiers

IRB-300003394

Identifier Type: -

Identifier Source: org_study_id