Salt and HMB Study

Not Applicable

Recruiting

• Conditions: Blood Pressure
• Interventions: Dietary Supplement: Sodium; Other: Placebo; Dietary Supplement: HMB

• Registration Number: NCT05515900
• Lead Sponsor: Augusta University

Brief Summary

Hypertension affects one-third of adults in the US. High salt diet is a key risk factor for elevated blood pressure (BP). The associations of gut microbiome with high salt diet and hypertension have been established in both animal and human studies. However, the underlying biological mechanisms linking sodium to BP elevation and gut microbiome alteration are not clear. Increasing evidence supports a pivotal role of leucine metabolism in hypertension. Leucine is initially catalyzed by the branched-chain amino acid aminotransferase enzyme (BCAT), producing α-ketoisocaproate (α-KIC), which can be further metabolized to β-hydroxy-β-methylbutyrate (HMB). Leucine/α-KIC/HMB metabolism pathway shows a promising involvement in the relationships among salt, gut microbiome, and elevated BP. Preliminary studies show that dietary sodium reduction increases circulating HMB, which is further associated with reduced BP, and that HMB treatment decreases Firmicutes/Bacteroidetes ratio, and increases α-diversity and gut microbiota-derived short-chain fatty acids (SCFAs). However, the leucine/α-KIC/HMB metabolism pathway has never been targeted in human studies. To establish causality, I propose a double-blind, two-stage randomized, placebo-controlled trial of sodium and HMB supplements for the following specific aims: Aim 1 will determine the effect of sodium supplement on leucine/α-KIC/HMB metabolism pathway. Aim 2 will determine the effect of HMB supplement on office BP and 24-hour ambulatory BP (Aim 2a), and α- and β-diversities and Firmicutes/Bacteroidetes ratio (Aim 2b). Secondary Aim will test the hypothesis that HMB supplement could partially block the detrimental effects of sodium intake on BP and gut microbiota. The proposed project would help to uncover the role of leucine/α-KIC/HMB metabolism pathway in salt-induced hypertension and the alteration in gut microbiome. Most importantly, the project will provide the training opportunities for me as a junior faculty, to study the new area of gut microbiome, acquire new experience and skills to conduct human trials. In addition, this project will generate rich preliminary data on the role of leucine/α-KIC/HMB metabolism pathway in salt-induced BP elevation, and test the feasibility for developing future NIH R01 project.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-10-01
• Study First Submitted: 2022-07-20
• Status Verified: 2022-08
• Study First Submitted QC: 2022-08-23
• Last Update Submitted: 2022-08-23
• Study First Posted: 2022-08-25
• Last Update Posted: 2022-08-25
• Primary Completion: 2024-09-30
• Study Completion: 2024-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• normotensive [SBP<140 mmHg and diastolic BP (DBP)<90 mmHg];
• self-identified black or white; c. aged from 18 to 65 years.

Exclusion Criteria

• taking medication that would affect BP or gut microbiome;
• being pregnant;
• with health conditions that would compromise sodium handling.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sodium active, HMB active	Sodium	The subjects in this group will take sodium pills of 2,000 mg/day from baseline to week 8, and take HMB pills of 3 g/day from week 5 to week 8 while on reduced-sodium diet.
Sodium active, HMB active	HMB	The subjects in this group will take sodium pills of 2,000 mg/day from baseline to week 8, and take HMB pills of 3 g/day from week 5 to week 8 while on reduced-sodium diet.
Sodium placebo, HMB active	HMB	The subjects in this group will take placebo pills from baseline to week 8, and take HMB pills of 3 g/day from week 5 to week 8 while on reduced-sodium diet.
Sodium placebo, HMB placebo	Placebo	The subjects in this group will take placebo pills from baseline to week 8 while on reduced-sodium diet.
Sodium active, HMB placebo	Sodium	The subjects in this group will take sodium pills of 2,000 mg/day from baseline to week 8, and take placebo pills of 3 g/day from week 5 to week 8 while on reduced-sodium diet.

Primary Outcome Measures

Name	Time	Method
Leucine/α-KIC/HMB metabolism	4 weeks	Changes in blood levels of metabolites leucine, α-KIC, and HMB from baseline to week 4.
Blood pressure	4 weeks	Changes in systolic and diastolic blood pressure from week 5 to week 8.
Gut microbiome	4 weeks	Changes in the composition of gut microbiome from week 5 to week 8.

Trial Locations

Locations (1)

Augusta University; 🇺🇸 Augusta, Georgia, United States