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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01HL132448-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Controlled hypertension | Subjects with controlled hypertension will provide a one time stool sample and a blood sample. |
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| 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. |
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| 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. |
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| Remodeled Resistent Hypertension | Subjects with controlled hypertension will provide a one time stool sample and a blood sample. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Reduction in BP is associated with changes in gut microbiota composition in RH subjects. | 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. |
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Inclusion Criteria:
Inclusion criteria for each subject group:
Exclusion Criteria:
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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.
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| Name | Affiliation | Role |
|---|---|---|
| Carl Pepline, MD | University of Florida | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
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| Cardiovascular Clinic at UF Health | Gainesville | Florida | 32610 | United States |
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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Stool Samples
| 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 | Stool samples from patients enrolled in NCT 02133871 that received minocycline | Baseline and 3 months |
| To determine if characterization of gut microbiota in at risk patients predicts long term care utilization and/or cardiovascular outcomes | Stool samples | Up to 5 years |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |