Salt and HMB Study

NCT ID: NCT05515900

Last Updated: 2022-08-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-01
• Study Completion Date: 2024-09-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Sodium

Intervention Type: DIETARY_SUPPLEMENT

Daily sodium supplementation of 2000 mg.

HMB

Intervention Type: DIETARY_SUPPLEMENT

Daily HMB supplementation of 3 g.

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.

Group Type: EXPERIMENTAL

Sodium

Intervention Type: DIETARY_SUPPLEMENT

Daily sodium supplementation of 2000 mg.

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.

Group Type: EXPERIMENTAL

HMB

Intervention Type: DIETARY_SUPPLEMENT

Daily HMB supplementation of 3 g.

Sodium placebo, HMB placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo pills that will be identical to sodium or HMB supplementations

Interventions

Sodium

Daily sodium supplementation of 2000 mg.

Intervention Type: DIETARY_SUPPLEMENT

HMB

Daily HMB supplementation of 3 g.

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Placebo pills that will be identical to sodium or HMB supplementations

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

American Heart Association

OTHER

Sponsor Role: collaborator

Augusta University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Augusta University

Augusta, Georgia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Li Chen, PhD

Role: CONTACT

lichen1@augusta.edu

7067211764

Other Identifiers

1810996

Identifier Type: -

Identifier Source: org_study_id