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The Role of Gut Microbiota in Hypertension

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ClinicalTrials.gov Identifier: NCT02188381
Recruitment Status : Recruiting
First Posted : July 11, 2014
Last Update Posted : August 27, 2018
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
University of Florida

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.

Condition or disease Intervention/treatment
Hypertension Other: Stool Sample and Blood Sample

Detailed Description:
This is a prospective cohort design. This study will enroll 388 subjects: 81 patients without HTN as a reference group, 81 patients with controlled HTN, 55 patients with uncontrolled HTN, 55 with remodeled RH, and 81 patients with RH to characterize gut microbiota composition. Subjects will provide stool samples for analysis. Subjects will also provide a blood sample for inflammatory marker and stem cell analysis.

Study Type : Observational
Estimated Enrollment : 398 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Role of Gut Microbiota in Hypertension
Actual Study Start Date : July 2014
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bowel Movement

Group/Cohort Intervention/treatment
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
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
Subjects with controlled hypertension will provide a one time stool sample and a blood sample.
Other: Stool Sample and Blood Sample
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.

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
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.

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
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.

Remodeled Resistent Hypertension
Subjects with controlled hypertension will provide a one time stool sample and a blood sample.
Other: Stool Sample and Blood Sample
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.




Primary Outcome Measures :
  1. Characterize gut microbiota composition at phylum level [ Time Frame: 24 hours ]
    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.

  2. Characterize gut microbiota composition at genus level [ Time Frame: 24 hours ]
    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.


Secondary Outcome Measures :
  1. Reduction in BP is associated with changes in gut microbiota composition in RH subjects. [ Time Frame: Baseline, 3 months ]
    Stool samples from patients enrolled in NCT 02133871 that received minocycline medication for resistant hypertension. Will be used to analyze the composition of the microbiota and data (taxonomic assignment) will be analyzed using QIIMEv1.3 pipeline to enumerate microbial population between samples derived from the cohorts.

  2. IS hypertension associated with increased sympathetic activity and decreased parasympathetic activity and whether minocycline or other tetracyclines are effective to improve this balance [ Time Frame: Baseline and 3 months ]
    Stool samples from patients enrolled in NCT 02133871 that received minocycline

  3. To determine if characterization of gut microbiota in at risk patients predicts long term care utilization and/or cardiovascular outcomes [ Time Frame: Up to 5 years ]
    Stool samples


Biospecimen Retention:   Samples With DNA
Stool Samples


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
Criteria

Inclusion Criteria:

  • age >18 and <80
  • is competent and willing to provide consent

Inclusion criteria for each subject group:

  • Control subjects will have a systolic BP <140mmHg with no cardiovascular disease
  • Patients with controlled hypertension
  • Resistant hypertension subjects will have systolic blood pressure (BP) ≥140 mmHg despite ≥3 anti-hypertensive medications of different classes
  • Subjects participating in NCT 02133872 will be eligible to participate

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02188381


Contacts
Contact: Eileen M Handberg, PhD 352-273-8944 handbem@ufl.edu

Locations
United States, Florida
Cardiovascular Clinic at UF Health Recruiting
Gainesville, Florida, United States, 32610
Contact: Eileen M Handberg, PhD    352-273-8944    handbem@ufl.edu   
Principal Investigator: Carl J Pepine, MD         
Sub-Investigator: Yanfei Qi, PhD         
Principal Investigator: Eileen M Handberg, PhD         
Sponsors and Collaborators
University of Florida
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Carl Pepline, MD University of Florida

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT02188381     History of Changes
Other Study ID Numbers: IRB201400233-N
1R01HL132448-01 ( U.S. NIH Grant/Contract )
First Posted: July 11, 2014    Key Record Dates
Last Update Posted: August 27, 2018
Last Verified: August 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Florida:
Resistant Hypertension
Uncontrolled Hypertension

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases