Salt and HMB Study

Blood Pressure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05515900
• Other study ID #: 1810996
• Status: Recruiting
• Phase: N/A
• Start date: October 1, 2021
• Est. completion date: September 30, 2024

Study information

• Verified date: August 2022
• Source: Augusta University
• Contact: Li Chen, PhD
• Phone: 7067211764
• Email: lichen1[@]augusta.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: September 30, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Blood Pressure

Intervention

Dietary Supplement:
• Sodium
Daily sodium supplementation of 2000 mg.
• HMB
Daily HMB supplementation of 3 g.

Other:
• Placebo
Placebo pills that will be identical to sodium or HMB supplementations

Locations

Country	Name	City	State
United States	Augusta University	Augusta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Augusta University	American Heart Association

Country where clinical trial is conducted

United States, 

Outcome

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