Salt Sensitivity Evaluation Via N-of-1 Trials (SENSE-Salt) (SENSE-Salt)

Determining the Presence of Salt Sensitivity in Individuals With Elevated Blood Pressure Through Dietary Salt Interventions: A Series of N-of-1 Trials

Study Title: Determining the Presence of Salt Sensitivity in Individuals With Elevated Blood Pressure Through Dietary Salt Interventions: A Series of N-of-1 Trials

Objective: To evaluate whether there are differences in blood pressure responses to dietary sodium intake between salt-sensitive and salt-resistant individuals, as identified through a salt sensitivity test. The study will use repeated dietary interventions with varying sodium content (high-sodium, low-sodium) to assess blood pressure responses in each individual, aiming to determine whether salt sensitivity is a present characteristic.

Study Design: This study will utilize an N-of-1 randomized controlled trial design. It consists of two phases:

Salt Sensitivity Screening: A 2-week chronic salt-loading test will be used to identify salt-sensitive and salt-resistant individuals.

N-of-1 Trial: The identified salt-sensitive and salt-resistant individuals will undergo a 6-week N-of-1 trial, consisting of three cycles, with each cycle including one week of low-sodium diet and one week of high-sodium diet. This design aims to assess individual blood pressure responses to changes in sodium intake.

Sample Size: A total of 72 participants will be recruited for the salt sensitivity screening, with an expected 24 participants proceeding to the N-of-1 trial.

Study Population: Healthy individuals aged 20-65 years, not on antihypertensive medication or with a stable regimen for at least 3 months, with systolic blood pressure between 110-159 mmHg and diastolic blood pressure between 70-99 mmHg, who are able to eat at the research center.

Primary Outcome: Reproducibility of salt sensitivity response classification. Secondary Outcomes: Changes in mean arterial pressure, systolic and diastolic blood pressure; exploratory outcomes such as sleep, mood, gut microbiome, metabolomics; safety outcomes including hypotension and hyponatremia.

Study Overview

• Status: Not yet recruiting
• Conditions: Hypertension; Salt-Sensitivity of Blood Pressure
• Intervention / Treatment: Other: High-Sodium Diet; Other: Low-Sodium Diet

Detailed Description

Study Title: Determining the Presence of Salt Sensitivity in Individuals With Elevated Blood Pressure Through Dietary Salt Interventions: A Series of N-of-1 Trials

Objective:

1. Primary Objective: To assess whether there are differences in blood pressure responses between salt-sensitive and salt-resistant individuals.
2. Exploratory Objectives: To explore the effects of different sodium-content diets on individual pulse, sleep, and mood; to evaluate whether a low-sodium diet increases the incidence of hypotension; and to identify metabolic differences associated with salt sensitivity.

Study Design: This study will utilize a two-phase N-of-1 randomized controlled trial design. It consists of the following phases:

1. Salt Sensitivity Screening: Participants will undergo a 2-week dietary intervention (1 week of high-sodium diet: 200 mmol/day; 1 week of low-sodium diet: 85 mmol/day). Salt sensitivity will be determined by comparing changes in mean arterial pressure (MAP) between the high-sodium and low-sodium periods (△MAP). Individuals with △MAP ≥5 mmHg and in the upper 1/6 of the population will be classified as salt-sensitive (SS), while those with △MAP <5 mmHg and in the lower 1/6 will be classified as salt-resistant (SR).
2. N-of-1 Trial: The identified salt-sensitive and salt-resistant individuals will undergo a 6-week N-of-1 trial, consisting of three cycles. Each cycle will last 2 weeks (1 week of high-sodium diet and 1 week of low-sodium diet). This design aims to assess individual blood pressure responses to changes in sodium intake.

Sample Size: A total of 72 participants will be recruited for the salt sensitivity screening, with an expected 24 participants proceeding to the N-of-1 trial.

Study Population: Healthy individuals aged 20-65 years, not on antihypertensive medication or with a stable regimen for at least 3 months, with systolic blood pressure between 110-159 mmHg and diastolic blood pressure between 70-99 mmHg, who are able to eat at the research center.

Primary Outcome: Reproducibility of salt sensitivity response classification. Secondary Outcomes:Changes in mean arterial pressure, systolic and diastolic blood pressure; exploratory outcomes such as sleep, mood, gut microbiome, and metabolomics; and safety outcomes including hypotension and hyponatremia.

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yifang Yuan; Phone Number: 0086-17310387323; Email: yyfjulie@163.com

Study Locations

• China
  • Beijing, China
    • Peking University
    • Contact: Yifang Yuan; Phone Number: 0086-17310387323; Email: yyfjulie@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Phase 1: Salt Sensitivity Screening

Inclusion:

1. Signed informed consent for the salt sensitivity test.
2. Systolic blood pressure between 110-159 mmHg and diastolic blood pressure between 70-99 mmHg.
3. Not taking any antihypertensive medication, or have had a stable antihypertensive regimen for the past three months and agree not to adjust their medication during the study period.
4. Able to comply with consuming the study-provided diet throughout the study period.

Exclusion:

1. Special dietary requirements, such as allergies to common foods (e.g., eggs, seafood, peanuts), or conditions like asthma, irritable bowel syndrome, lactose intolerance, chronic kidney disease stage 4 or higher, history of gastrointestinal surgery, or special dietary needs due to other illnesses, surgery, or weight loss.
2. Diagnosed with chronic diseases: any malignancy with a life expectancy of less than one year; chronic heart failure, severe depression or other mental disorders, long-term bedridden status, or mobility limitations.
3. Experienced acute myocardial infarction or stroke within the past 6 months.
4. Acute illnesses such as upper respiratory tract infection, fever, or severe diarrhea that have not yet resolved.
5. Alcohol abuse.
6. Pregnant or breastfeeding women, or women planning to become pregnant.
7. Individuals who are deaf, mute, or have cognitive impairments that hinder communication.

Phase 2: N-of-1 Trial

Inclusion:

1. Classified as salt-sensitive or salt-resistant through the Phase 1 screening:
2. Salt-Sensitive (SS) Group: Participants with a change in mean arterial pressure (ΔMAP) ≥ 5 mmHg and in the upper 1/6 of the distribution of ΔMAP from the salt sensitivity test.
3. Salt-Resistant (SR) Group: Participants with a change in mean arterial pressure (ΔMAP) < 5 mmHg and in the lower 1/6 of the distribution of ΔMAP from the salt sensitivity test.
4. Signed informed consent for the n-of-1 trial.

Exclusion:

1. Failed to complete the salt sensitivity test as required, or consumed less than 80% of the study-provided meals during the salt sensitivity test (i.e., fewer than 34 meals over 14 days).
2. Experienced adverse events during the salt sensitivity test that, in the investigator's judgment, make it inappropriate to continue in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: High-Sodium Diet; Daily dietary salt intake: 12 g （sodium 200 mmol）	Other: High-Sodium Diet; Daily dietary salt intake: 12 g （sodium 200 mmol）; Other: Low-Sodium Diet; Daily dietary salt intake: 5 g （sodium 85 mmol）
Other: Low-Sodium Diet; Daily dietary salt intake: 5 g （sodium 85 mmol）	Other: High-Sodium Diet; Daily dietary salt intake: 12 g （sodium 200 mmol）; Other: Low-Sodium Diet; Daily dietary salt intake: 5 g （sodium 85 mmol）

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reproducibility of salt-sensitivity classification	The proportion of participants with concordant salt-sensitivity classification across repeated assessments	Salt-sensitivity test: baseline through Day 14 N-of-1 trial: baseline through Day 42

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in mean arterial pressure	the change in mean arterial pressure (MAP) is defined as the difference between the mean follow-up MAP during the high-sodium period and the mean follow-up MAP during the low-sodium period.	Salt-sensitivity test: baseline through Day 14 N-of-1 trial: baseline through Day 42
The change in systolic blood pressure	the change in systolic blood pressure (SBP) is defined as the difference between the mean follow-up SBP during the high-sodium period and the mean follow-up SBP during the low-sodium period.	Salt-sensitivity test: baseline through Day 14 N-of-1 trial: baseline through Day 42
The change in diastolic blood pressure	the change in diastolic blood pressure (DBP) is defined as the difference between the mean follow-up DBP during the high-sodium period and the mean follow-up DBP during the low-sodium period.	Salt-sensitivity test: baseline through Day 14 N-of-1 trial: baseline through Day 42
Incidence of hypotension	Hypotension is defined as at least two blood pressure readings <90/60 mm Hg during follow-up, or symptomatic hypotension diagnosed by a physician during treatment.	From baseline of the salt-sensitivity test through the end of the n-of-1 trial, up to 8 weeks
The incidence of hyponalemia	A new case of hyponalemia is defined as having serum sodium<135 mmol/L in any follow-up or during the study period with normal serum sodium at the baseline, regardless of clinical manifestations.	From baseline of the salt-sensitivity test through the end of the n-of-1 trial, up to 8 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Home self-measured blood pressure	Home self-measured blood pressure is defined as the values obtained by participants using the electronic sphygmomanometer provided by the research team.	From baseline of the salt-sensitivity test through the end of the n-of-1 trial, up to 8 weeks
The change in spot urine sodium	the change in spot urine sodium is defined as the difference between the mean follow-up urine sodium during the high-sodium period and the mean follow-up urine sodium during the low-sodium period.	Salt-sensitivity test: baseline, day 7, day 14 follow-up. N of 1 trial: baseline, day 7, day 14, day 21, day 28, day 35, day 42 follow-up.
Total sleep time during the study	Measured using continuous wristband monitoring. Total sleep time will be recorded in minutes per night.	From baseline of the salt-sensitivity test through the end of the n-of-1 trial, up to 8 weeks
Number of nighttime awakenings during the study	Measured using continuous wristband monitoring. The number of nighttime awakenings will be recorded as events per night.	From baseline of the salt-sensitivity test through the end of the n-of-1 trial, up to 8 weeks
Changes in mood parameters	Measured with the Center for Epidemiologic Studies Depression Scale-10 item version (CESD-10). The total score ranges from 0 to 30, with higher scores indicating worse depressive symptoms/mood status.	From baseline of the salt-sensitivity test through Day 42 of the n-of-1 trial, up to 8 weeks
Fecal metabolites	Fecal metabolomic profiles will be analyzed using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS).	Salt-sensitivity test: baseline, day 7, day 14 follow-up. N of 1 trial: baseline, day 7, day 14, day 21, day 28, day 35, day 42 follow-up.
Fecal microbiota	Gut microbial composition and functional features will be assessed using shotgun metagenomic sequencing of fecal samples.	Salt-sensitivity test: baseline, day 7, day 14 follow-up. N of 1 trial: baseline, day 7, day 14, day 21, day 28, day 35, day 42 follow-up.
Metabolomics profiling	Metabolomic profiling will be performed using urine and fecal samples collected during follow-up. Baseline serum samples will also be included in the metabolomic analyses.	Salt-sensitivity test: baseline, day 7, day 14 follow-up. N of 1 trial: baseline, day 7, day 14, day 21, day 28, day 35, day 42 follow-up.

Collaborators and Investigators

• Sponsor: Peking University
• Investigators: Principal Investigator: Yifang Yuan, Peking University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: May 17, 2026
• First Submitted That Met QC Criteria: May 22, 2026
• First Posted (Actual): May 29, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: blood pressure; salt-sensitivity
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertension; Therapeutics; Diet, Food, and Nutrition; Physiological Phenomena; Nutritional Physiological Phenomena; Diet Therapy; Nutrition Therapy; Diet; Diet, Sodium-Restricted
• Other Study ID Numbers: 1052-25187

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No