Evaluation of Intestinal Microbiota Manipulation to Treat Resistant Hypertension

Summary

The gastrointestinal tract begins its colonization shortly after birth. During the first two years of life, gut microbiota is unstable and less diverse than in adulthood. Its complexity and diversity are modified by external factors that shall influence the composition of gut microbiota, especially the diet, the personal hygiene and the food cleansing, as well as the chronic use of antibiotics. Some recent evidence suggests that the microbiome may affect the likelihood of various diseases, including obesity, diabetes and cardiovascular disease. Among cardiovascular diseases, hypertension (HT) accompanied with increased cardiovascular morbidity and mortality. Hypertensive individuals may present controlled blood pressure (use of up to 03 antihypertensive drugs) or resistant without blood pressure control, even in the use of 03 or more antihypertensive drugs. Objectives: Evaluating gut microbiota of resistant hypertensive individuals, we shall compare it with those of normotensive and controlled hypertensive individuals. The resistant hypertensive ones will also receive a therapeutic intervention with prebiotics to determine if the changes in microbiota and in the production of microbiota metabolites can lower blood pressure. Methods: The study will be composed of two phases, one observational and one interventional. The observational phase will be composed of adults of both genders, aged between 40 and 70 years old, divided into three groups: normotensive, controlled hypertensive and resistant hypertensive individuals. Nutritional assessment, biochemistry and stool analysis will be performed to study the microbiota in all groups, in addition to the evaluation of peripheral and central hemodynamic parameters. The intervention phase will consist of a, randomized, double-blinded, placebo-controlled crossover study using a prebiotic formula during 04 weeks in the resistant hypertensive group. After a washout period of 4 weeks, the protocol will be repeated in the other arm. Participants will visit the clinic in 4 occasions, which shall include biochemical tests \[for small chain fatty acids (SCFAs), noradrenaline, gut dysbiosis, immunomodulation\] and fecal sample collection (for SCFAs and gut microbiome determination), besides the evaluation of flow-mediated dilation and peripheral and central hemodynamic parameters.

Conditions

• Hypertension
• Resistant Hypertension

Interventions

DIETARY_SUPPLEMENT

Prebiotic

It shall be a double-blinded, randomized, placebo-controlled crossover study and treatment with prebiotic for 4 weeks. After a washout period of 4 weeks, the study protocol will be repeated in the other arm. Participants will receive supplementary diet based on high-amylose cornstarch, which releases large amounts of SCFA (acetate and butyrate) in a sachet with a powder that must be dissolved in a glass of liquid to your choice, during 4 weeks (20 g 2x/day). Participants will undergo anthropometric, biochemistry and GUT microbiota assessment, before and after the end of the first phase of the crossover study. Later, when the inversion of the treatment groups occur all participants will also be subjected to the same procedures before and after the end of the second phase of the study.

Sponsors & Collaborators

• Sao Jose do Rio Preto Medical School

  collaborator OTHER

• Hospital de Base

  lead OTHER

Principal Investigators

• José F Vilela-Martin, MD PhD FAHA · State Medical School at São José do Rio Preto (FAMERP), São Paulo, Brazil

• Francine Z Marques, PhD · School of Biological Sciences, Faculty of Science, Monash University, Melbourne, VIC, Australia

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

40 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2019-02-01

Primary Completion

2021-06-30

Completion

2022-01-31

Countries

• Brazil

Study Locations