Salt and Gut Study

Study Overview
=================
Brief Summary
-----------------
High sodium intake is a significant risk factor for hypertension. Recently, animal studies connect high sodium intake to the gut-immune axis and highlight the gut microbiome as a potential therapeutic target to counteract salt-sensitive conditions and hypertension. The objective of this project is to determine the effects of high salt intake on gut microbiota composition and gut intestine barrier integrity, leading to increased BP in humans. The investigators also hypothesize that high salt intake affects the gut microbiome in a sex-specific manner. In this pilot study, The investigators also test whether telehealth or in-person nutritional coaching help to decrease dietary sodium intake and improve diet quality

Detailed Description
-----------------
The investigators will conduct a randomized, double-blind, placebo-controlled trial in normotensive and stage 1 hypertensive drug naïve participants (age 18-50 years, equal distribution of blacks and whites, and males and females, BP <140/90 mmHg). The average intake of sodium in the American diet is 3,400 mg per day. The average recommended dose is 2,300 mg per day. Eligible participants will be enrolled and provided with one-hour in-person/telehealth nutritional counseling at the GPI to reduce their sodium intake by 1,100 mg per day to achieve the sodium intake of 2,300 mg/day. Participants will then be randomized to receive either placebo or salt pills of 2,000 mg per day for four weeks while continuously receiving weekly telehealth nutritional counseling. The salt group's sodium intake will be 4,300 mg per day, while the sodium intake in the placebo group will be 2,300 mg per day. Participants will have a follow-up visit at six months after the 4-week sodium intervention. Participants will be tested four times (Figure 1). Participants will receive the first 1-hour in-person/telehealth nutrition counseling at GPI (baseline) and three weekly telehealth nutrition counseling during the 4-week intervention period.

Official Title
-----------------
High Sodium Intake, Gut Microbiome and Blood Pressure Control

Conditions
-----------------
High Blood Pressure

Intervention / Treatment
-----------------
* Dietary Supplement: Salt pills
* Dietary Supplement: Placebo pills


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Aged between 18-50 years African Americans (AAs) or European Americans (EAs) BP <140/90 mmHg Not on any prescription medications Normal kidney function (eGFR ≥ 90 ml/min/1.73 m2) Exclusion criteria: Pregnant or nursing Previous diagnosis of major cardiovascular diseases including myocardial infarction, congestive heart failure or stroke, diabetes, autoimmune, chronic liver and kidney disease Previous diagnosis of Crohn's disease or any other intestinal conditions Previous diagnosis of major lung diseases such as chronic obstructive pulmonary disease (COPD) Previous diagnosis of cancer Alcohol and drug abuse.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomized, double-blind, placebo-controlled trial. Half the participants will be in placebo arm, the other half will be in salt arm.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High sodium<br>Subjects will be counseled to consume a diet with 2,300 mg/d sodium which they will supplement with pills containing salt to achieve an intake of 4,300 mg/d sodium for 4 weeks. | Dietary Supplement: Salt pills<br>* Subjects will supplement salt pills with meals.<br>|
| Placebo Comparator: Placebo<br>Subjects will be counseled to consume a diet with 2,300 mg/d sodium and will supplement with taking placebo pills for 4 weeks. | Dietary Supplement: Placebo pills<br>* Subjects will supplement placebo pills with meals.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gut microbiota diversity using 16s rRNA Sequencing | Subjects will be provided instructions and kits on how to collect feces and saliva samples. Saliva samples will be collected on the testing day. Feces sample will be collected on the testing day if possible; if not, it will be brought back the following day. DNA will be extracted from collected feces and saliva samples using the MoBioPowerSoil kit. The V3-V5 region of the 16S rRNA will be amplified and sequenced using the Illumina MiSeq platform. The outcome variables for microbiome data will be alpha diversity, beta diversity, and overall composition. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gut intestine barrier integrity measured by non-invasive biomarkers | Gut intestine barrier function will be determined by non-invasive biomarkers. Plasma LPS, I-FABP, DAO, zonulin, IL-6, TLR4 will be measured. | 4 weeks |