Clinical trial NCT05388032: Sodium Lowering Vascular Effects Trial
Official title: A Mechanistic Trial of Dietary Sodium Reduction on Vascular Structure and Function
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Endothelial Dysfunction
Vascular Stiffness
Left Ventricular Hypertrophy
Left Ventricular Dysfunction
Lead sponsor: Tulane University
Sponsor class: OTHER
Collaborators: name: Johns Hopkins University
First posted: 2022-05-24
Enrollment: 256
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible participants will be randomized 1:1 into the dietitian-led behavioral intervention and usual diet.
Primary purpose: BASIC_SCIENCE

Brief summary: The proposed mechanistic trial will test the effect of dietary sodium reduction on cardiac and vascular structure and function in those with elevated blood pressure or hypertension. Findings from this study will fill the knowledge gap on the underlying mechanisms of dietary sodium intake on cardiovascular disease risk in addition to blood pressure and could provide further evidence on sodium reduction for the prevention of cardiovascular disease.

Detailed description: High dietary sodium intake increases risk of cardiovascular disease (CVD) independent of established risk factors, including blood pressure (BP). Non-BP mediated mechanisms underlying the increased risk of CVD associated with dietary sodium intake are not well understood, but observational studies suggest direct target organ damage in the heart and vasculature might play an important role. Little evidence exists from randomized controlled trials (RCTs) on target organ effects of dietary sodium reduction, and the National Academy of Medicine has recommended future research to "test the effects of different sodium intake levels on endothelial and vascular function" in order to "to better characterize the relationship between sodium intake and chronic disease". The overall objective of the proposed mechanistic trial is to test the effect of dietary sodium reduction on cardiac and vascular structure and function. Specifically, the proposed trial will test whether dietary sodium reduction (targeting a dietary sodium intake of \<2,300 mg/day) will improve left ventricular mass index (LVMI), left ventricular global longitudinal strain (LVGLS), carotid-femoral pulse wave velocity (cfPWV), and flow-mediated dilation (FMD) compared to usual intake. Additionally, we will test whether this effect is independent from BP reduction. We will recruit 256 people with elevated BP or hypertension from the greater New Orleans area and randomly assign them to a dietitian-led behavioral intervention aimed at decreasing dietary sodium intake to \<2,300 mg/day for 12 months or to a usual diet. Study outcomes, including cardiac magnetic resonance imaging (CMR)-determined LVMI and LVGLS, cfPWV, and FMD, will be measured at baseline, 6-month, and 12-month clinic visits using standardized protocols with stringent quality control. These outcomes are validated biomarkers for target organ damage and predict the risk of clinical CVD events. In primary analyses, the effect of sodium reduction on each subclinical CVD endpoint will be compared between the sodium reduction and usual diet groups according to the intention-to-treat principle without adjusting for covariates. In secondary analyses, changes in ambulatory and clinical BP will be adjusted to assess the BP-independent effect of dietary sodium reduction on each subclinical CVD endpoint. The proposed trial has 85% statistical power to detect a clinically significant difference in changes of the four co-primary outcomes (10 g/m2 in LVMI, 1.3% in LVGLS, 0.9 m/s in cfPWV, and 1.1% in FMD) over 12 months between the two groups at a 2-sided significance level of 0.0125 (0.05/4). Findings from this trial will fill the knowledge gap of the underlying mechanisms of dietary sodium intake on CVD risk and provide further evidence on sodium reduction for CVD prevention.

Eligibility criteria: Inclusion Criteria:

* Men or women aged ≥40 years. Individuals \<40 years are at a low risk for clinical and subclinical CVD
* Elevated BP or hypertension (systolic BP ≥120 mmHg and diastolic BP ≥80 mmHg with or without use of antihypertensive medications)

Exclusion Criteria:

* Glomerular filtration rate (eGFR) \<30 or end-stage renal disease (kidney transplant or chronic dialysis)
* History of cardiovascular disease
* Shift worker or regularly work at night
* Cancer requiring chemotherapy or radiation treatment in the previous two years
* Current pregnancy or breastfeeding or plans to become pregnant during the study
* Consumption of ≥21 alcoholic drinks/week
* Current participation in another lifestyle intervention or drug trial
* Current residence or planned residence that makes it difficult to meet trial requirements
* Other concerns regarding ability to meet trial requirements (at the discretion of the study coordinator)

Primary outcomes:
measure: Change in Left Ventricular Global Longitudinal Strain (LVGLS) from baseline to 12 months
timeFrame: 12 months
measure: Change in Left Ventricular Mass Index (LVMI) from baseline to 12 months
timeFrame: 12 months
measure: Change in Pulse Wave Velocity (PWV) from baseline to 12 months
timeFrame: 12 months
measure: Change in Flow-Mediated Dilation (FMD) from baseline to 12 months
timeFrame: 12 months
Secondary outcomes:
measure: Left Ventricular Volumes
timeFrame: Baseline, 6 months, and 12 months
measure: Left Atrial Maximum and Minimum Volume
timeFrame: Baseline, 6 months, and 12 months
measure: Left Atrial Ejection Fraction
timeFrame: Baseline, 6 months, and 12 months
measure: Left Atrial Global Strain
timeFrame: Baseline, 6 months, and 12 months
measure: Aortic Pulse Wave Velocity
timeFrame: Baseline, 6 months, and 12 months
Other outcomes:
Locations:
city: New Orleans
country: United States
facility: Tulane University Office of Health Research
state: Louisiana
Study officials:
affiliation: Tulane University
name: Katherine T Mills, PhD
role: PRINCIPAL_INVESTIGATOR
References: