Evaluation of Intestinal Microbiota Manipulation to Treat Resistant Hypertension

NCT04398693 | Unknown

• 1 other identifier: VALORIS
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Microbiota; Gastrointestinal Microbiome; Hypertension; Randomized Controlled Study; Prebiotics

Outcome Measures

Primary Outcomes (1)

• Change of blood pressure

  This study will provide a background for the use of a new strategy to lower the BP. The study primary outcome will be to observe the lowering of blood pressure.

  12 weeks

Secondary Outcomes (2)

• Change of inflammatory activity

  12 weeks

• Microbiota modulation

  12 weeks

Study Arms (3)

Normotensive Patients

NO INTERVENTION

40 normotensive patients with systolic BP (SBP) \< 140 mmHg and diastolic BP (DBP) \< 90 mmHg at the office, without the use of antihypertensive drugs and evaluated through ambulatory blood pressure monitoring (ABPM) to confirm normotension (BP \< 130/80 mmHg) and the exclusion of possible masked hypertension.

Controlled Hypertensive Patients

NO INTERVENTION

40 controlled hypertensive patients using up to three antihypertensive drugs with SBP \< 130 mmHg and DBP \< 80 mmHg evaluated through 24 hours ambulatory blood pressure monitoring (ABPM).

Resistant Hypertensive Patients

ACTIVE COMPARATOR

The study will be double-blinded, randomized, placebo-controlled crossover Initially, 20 individuals of the resistant hypertensive group will take prebiotic for 4 weeks, while other 20 individuals this group will use placebo. After a washout period of 4 weeks, the study protocol will be repeated in the other arm.

Dietary Supplement: Prebiotic

Interventions

Prebiotic DIETARY_SUPPLEMENT

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.

Resistant Hypertensive Patients

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be normotensive, controlled hypertensive or resistant hypertensive.
• Body Mass Index (BMI) \&lt; 35 kg/m 2 .
• If diabetic, glycated hemoglobin must be ≤ 9.0%.
• Agree and sign the Free Informed Consent Form (FICF).

You may not qualify if:

• BMI ≥ 35 kg/m 2 ;
• Urinary Sodium ≥ 200mEq/L in 24-hour urine;
• Bariatric Surgery;
• Recent use of antibiotics or probiotics (\&lt;3 months);
• Prior Cardiovascular Disease: Acute Myocardial Infarction, Stroke, Heart Failure, Angina Pectoris, Peripheral Arterial Insufficiency;
• Chronic kidney disease (glomerular filtration rate (GFR) \&lt; 30 mL/min/m 2 );
• Chronic Disease limiting participation at the study or life expectancy (e.g.: cancer, among others);
• Gastrointestinal diseases (including inflammatory bowel disease, celiac disease, lactose intolerance, chronic pancreatitis or other disabsortive disease)
• Pregnant or having the intension of become pregnant in the next two years;
• Participation in any other clinical studies in the past six months.

Sponsors & Collaborators

• Hospital de Base: lead
• Sao Jose do Rio Preto Medical School: collaborator

Study Sites (1)

State Medical School at São José do Rio Preto (FAMERP), São Paulo, Brazil

São José do Rio Preto, São Paulo, 15090-000, Brazil

RECRUITING

MeSH Terms

Conditions

Hypertension

Interventions

Prebiotics

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dietary Fiber; Dietary Carbohydrates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Food; Diet, Food, and Nutrition; Physiological Phenomena; Dietary Supplements; Food and Beverages

Study Officials

• José F Vilela-Martin, MD PhD FAHA

  State Medical School at São José do Rio Preto (FAMERP), São Paulo, Brazil

  PRINCIPAL INVESTIGATOR

• Francine Z Marques, PhD

  School of Biological Sciences, Faculty of Science, Monash University, Melbourne, VIC, Australia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

José F Vilela-Martin, MD PhD FAHA

CONTACT

+55 (17) 3201-5727; vilelamartin@uol.com.br

Letícia A Barufi-Fernandes, Master

CONTACT

+55 (17) 98134-4296; nutricionistaleticiabarufi@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator and Clinical Professor

Model Details: 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 acetate and butyrate in a sachet with a powder that must be dissolved in a glass of liquid 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. Afterwards, endothelial function studies, evaluating the vasodilation mediated by flow (flow-mediated dilation-FMD), and peripheral and central hemodynamics are also performed before and after the two treatment periods.

Study Record Dates

• First Submitted: October 6, 2019
• First Posted: May 21, 2020
• Study Start: February 1, 2019
• Primary Completion: June 1, 2021
• Study Completion: January 1, 2022
• Last Updated: February 25, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)