The Role of Gut Microbiota in Hypertension

NCT02188381 | Completed

• 2 other identifiers: IRB201400233-N1R01HL132448-01
• Study Type: observational
• Target: 292
• Locations: 1 country
• Sites: 1

Brief Summary

Hypertension is the single most prevalent risk factor for heart diseases, heart failure, kidney failure and stroke. About 1 in 3 adults in the United States have hypertension. Approximately 28-30% of hypertensive patients suffer from resistant hypertension (RH). Inflammation has been implicated in the pathogenesis of the hypertension. Additional data suggests the involvement of gut microbiota in host normal cardiovascular functions and pathophysiology. Accumulating evidence demonstrates that antibiotic treatment benefits patients with acute coronary syndromes and reduces the incidence of ischemic cardiovascular events. Even though these studies did not address effects of antibiotic treatment on the gut microbiota, it is possible that gut microbiota could affect neurologic inflammation. Finally, intestinal microbiota has recently been proposed to modulate blood pressure (BP) through production of short-chain fatty acids. In order to investigate this, the investigators hypothesize that gut microbiota is involved in the neuroinflammation-mediated initiation and establishment of RH, and targeting gut microbiota by minocycline would produce beneficial outcomes in RH.

Conditions

Hypertension

Keywords

Resistant Hypertension (RH); Uncontrolled Hypertension

Outcome Measures

Primary Outcomes (2)

• Characterize gut microbiota composition at phylum level

  Stool samples to analyze the composition of the microbiota, extracted bacterial genomic DNA will be used as a template for PCR reactions targeting the V4-V5 variable regions of the 16S rRNA gene. Amplicons generated from the PCR will be run on the Illumina MiSeq sequencing platform available in our laboratory to profile microbial communities at phylum level.

  24 hours

• Characterize gut microbiota composition at genus level

  Stool samples to analyze the composition of the microbiota, extracted bacterial genomic DNA will be used as a template for PCR reactions targeting the V4-V5 variable regions of the 16S rRNA gene. Amplicons generated from the PCR will be run on the Illumina MiSeq sequencing platform available in our laboratory to profile microbial communities at genus level.

  24 hours

Secondary Outcomes (3)

• Reduction in BP is associated with changes in gut microbiota composition in RH subjects.

  Baseline, 3 months

• IS hypertension associated with increased sympathetic activity and decreased parasympathetic activity and whether minocycline or other tetracyclines are effective to improve this balance

  Baseline and 3 months

• To determine if characterization of gut microbiota in at risk patients predicts long term care utilization and/or cardiovascular outcomes

  Up to 5 years

Study Arms (5)

Normal controls without hypertension

Control subjects will have a systolic BP \<140mmHg with no cardiovascular disease. These subjects will provide a one time stool sample and a blood sample.

Other: Stool Sample and Blood Sample

Controlled hypertension

Subjects with controlled hypertension will provide a one time stool sample and a blood sample.

Other: Stool Sample and Blood Sample

Resistant hypertension

Resistant hypertension subjects will have systolic blood pressure (BP) ≥140 mmHg despite ≥3 anti-hypertensive medications of different classes. These subjects will provide a one time stool sample and a blood sample.

Other: Stool Sample and Blood Sample

Prior enrolled in NCT 02133872

These subject will be asked to provide two stool samples and two blood samples. One at baseline and one after 3 months of therapy.

Other: Stool Sample and Blood Sample

Remodeled Resistent Hypertension

Subjects with controlled hypertension will provide a one time stool sample and a blood sample.

Other: Stool Sample and Blood Sample

Interventions

Stool Sample and Blood Sample OTHER

All subjects will provide a stool sample and a blood sample at baseline. Subjects in NCT02133872 will provide a second stool sample and blood sample at their 3 month visit.

Controlled hypertension; Normal controls without hypertension; Prior enrolled in NCT 02133872; Remodeled Resistent Hypertension; Resistant hypertension

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study will initially enroll 10 patients without hypertension as normal controls, and 10 patients with controlled hypertension and 10 patients with resistant hypertension to characterize gut microbiota. In addition, all patients enrolled in IRB# 102-2013 will be approached for possible participation.

You may qualify if:

• age \>18 and \<80
• is competent and willing to provide consent
• Control subjects will have a systolic BP \<140mmHg with no cardiovascular disease
• Patients with controlled hypertension
• Patients with uncontrolled hypertension
• Resistant hypertension subjects will have systolic blood pressure (BP) ≥140 mmHg despite ≥3 anti-hypertensive medications of different classes one of which should be a diuretic
• Patients who are no longer RH subjects and have normal blood pressure
• Subjects participating in NCT 02133872 will be eligible to participate

You may not qualify if:

• currently pregnant or have been pregnant in the last 6 months;
• antibiotic treatment within 2 months of study enrollment;
• currently taking a medication (e.g., antibiotic, anti-inflammatory agents, glucocorticoids or other immune modulating medications);
• unwilling to discontinue vitamin or supplements, including probiotics, potentially affecting gut microbiota (vitamins/supplements and medications that possibly affect the gut microbiota should be discontinued for at least 2wks prior to stool collection);
• history of intestinal surgery, inflammatory bowel disease, celiac disease, lactose intolerance, chronic pancreatitis or other malabsorption disorder.

Sponsors & Collaborators

• University of Florida: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Cardiovascular Clinic at UF Health

Gainesville, Florida, 32610, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Stool Samples

MeSH Terms

Conditions

Hypertension

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Carl Pepline, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2014
• First Posted: July 11, 2014
• Study Start: July 1, 2014
• Primary Completion: August 1, 2020
• Study Completion: August 1, 2020
• Last Updated: August 17, 2025

Record last verified: 2024-01

Locations

US (1)