Salt and HMB Study

NCT05515900 | Unknown

• 1 other identifier: 1810996
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Blood Pressure

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (4)

Sodium active, HMB active

EXPERIMENTAL

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; Dietary Supplement: HMB

Sodium active, HMB placebo

EXPERIMENTAL

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

Sodium placebo, HMB active

EXPERIMENTAL

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

Sodium placebo, HMB placebo

PLACEBO COMPARATOR

The subjects in this group will take placebo pills from baseline to week 8 while on reduced-sodium diet.

Other: Placebo

Interventions

Sodium DIETARY_SUPPLEMENT

Daily sodium supplementation of 2000 mg.

Sodium active, HMB active; Sodium active, HMB placebo

HMB DIETARY_SUPPLEMENT

Daily HMB supplementation of 3 g.

Sodium active, HMB active; Sodium placebo, HMB active

Placebo OTHER

Placebo pills that will be identical to sodium or HMB supplementations

Sodium placebo, HMB placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Augusta University: lead
• American Heart Association: collaborator

Study Sites (1)

Augusta University

Augusta, Georgia, 30912, United States

RECRUITING

MeSH Terms

Interventions

Sodium

Intervention Hierarchy (Ancestors)

Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals

Central Study Contacts

Li Chen, PhD

CONTACT

7067211764; lichen1@augusta.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2022
• First Posted: August 25, 2022
• Study Start: October 1, 2021
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2024
• Last Updated: August 25, 2022

Record last verified: 2022-08

Locations

US (1)