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

Official title

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

Overview

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.

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.

Interventions

• 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）

Primary outcome measures

• Reproducibility of salt-sensitivity classification [Time frame: Salt-sensitivity test: baseline through Day 14 N-of-1 trial: baseline through Day 42]

Secondary outcome measures (5)

• The change in mean arterial pressure [Time frame: Salt-sensitivity test: baseline through Day 14 N-of-1 trial: baseline through Day 42]
• The change in systolic blood pressure [Time frame: Salt-sensitivity test: baseline through Day 14 N-of-1 trial: baseline through Day 42]
• The change in diastolic blood pressure [Time frame: Salt-sensitivity test: baseline through Day 14 N-of-1 trial: baseline through Day 42]
• Incidence of hypotension [Time frame: From baseline of the salt-sensitivity test through the end of the n-of-1 trial, up to 8 weeks]
• The incidence of hyponalemia [Time frame: From baseline of the salt-sensitivity test through the end of the n-of-1 trial, up to 8 weeks]

Eligibility criteria

Phase 1: Salt Sensitivity Screening

Inclusion:

• Signed informed consent for the salt sensitivity test.
• Systolic blood pressure between 110-159 mmHg and diastolic blood pressure between 70-99 mmHg.
• 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.
• Able to comply with consuming the study-provided diet throughout the study period.

Exclusion:

• 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.
• 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.
• Experienced acute myocardial infarction or stroke within the past 6 months.
• Acute illnesses such as upper respiratory tract infection, fever, or severe diarrhea that have not yet resolved.
• Alcohol abuse.
• Pregnant or breastfeeding women, or women planning to become pregnant.
• Individuals who are deaf, mute, or have cognitive impairments that hinder communication.

Phase 2: N-of-1 Trial

Inclusion:

• Classified as salt-sensitive or salt-resistant through the Phase 1 screening:
• 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.
• 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.
• Signed informed consent for the n-of-1 trial.

Exclusion:

• 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).
• Experienced adverse events during the salt sensitivity test that, in the investigator's judgment, make it inappropriate to continue in the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Triple blind

Primary purpose

Prevention

Study locations

China · 1 center

• Peking University — Beijing

Identifiers

NCT: NCT07614724 · 1052-25187

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗