Salt and HMB Study

The Roles of HMB and Sodium in Blood Pressure Regulation and Gut Microbiome

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.

Study Overview

• Status: Recruiting
• Conditions: Blood Pressure
• Intervention / Treatment: Dietary supplement: Sodium; Dietary supplement: HMB; Other: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Li Chen, PhD; Phone Number: 7067211764; Email: lichen1@augusta.edu

Study Locations

• United States
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Recruiting
      • Augusta University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sodium active, HMB active; 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.	Dietary supplement: Sodium; Daily sodium supplementation of 2000 mg.; Dietary supplement: HMB; Daily HMB supplementation of 3 g.
Experimental: Sodium active, HMB placebo; 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.	Dietary supplement: Sodium; Daily sodium supplementation of 2000 mg.
Experimental: Sodium placebo, HMB active; 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.	Dietary supplement: HMB; Daily HMB supplementation of 3 g.
Placebo Comparator: Sodium placebo, HMB placebo; The subjects in this group will take placebo pills from baseline to week 8 while on reduced-sodium diet.	Other: Placebo; Placebo pills that will be identical to sodium or HMB supplementations

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Augusta University
• Collaborators: American Heart Association

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Anticipated): September 30, 2024
• Study Completion (Anticipated): September 30, 2024

Study Registration Dates

• First Submitted: July 20, 2022
• First Submitted That Met QC Criteria: August 23, 2022
• First Posted (Actual): August 25, 2022

Study Record Updates

• Last Update Posted (Actual): August 25, 2022
• Last Update Submitted That Met QC Criteria: August 23, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 1810996

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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