Antihypertensive Mechanisms of Minocycline in Resistant Hypertension

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified February 2026 by University of Florida
Sponsor
University of Florida
Information Provided by (Responsible Party)
University of Florida
Clinicaltrials.gov Identifier
NCT06246396
Other Study ID Numbers:
IRB202301939
First Submitted
January 29, 2024
First Posted
February 6, 2024
Last Update Posted
March 5, 2026
Last Verified
February 2026

ClinicalTrials.gov processed this data on March 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

One hundred twenty patients with treatment-resistant hypertension will be enrolled. A total of 34 patients (17 from each treatment arm), who are participants in the main study, will also be enrolled in a substudy that includes neuroimaging. The study will last 3 months, and will include 3 visit time points (screening, randomization visit, 3-month follow-up visit).

Participants will be randomly assigned, in a 1:1 allocation, to minocycline 100 mg twice per day, or matching placebo, each provided by the study, and investigators will be blinded to treatment assignment.

At the baseline and 3-month follow-up visit, subjects will undergo:

* A comprehensive medical history and examination, including assessment of antihypertensive treatment history

* A series of behavioral activity questionnaires

* Blood tests (plasma renin activity, aldosterone, catecholamines, serum creatinine, lipid panel, hemoglobin a1c, as well as various biomarkers of immune and inflammatory activity, and gut leakiness markers)

* Urine/saliva tests for antihypertensive adherence

* Gut microbiota profiling via whole metagenomic sequencing of stool samples

* Blood pressure (BP) measurement, including unattended office BP and 24-hour ambulatory BP

Subjects enrolled in the neuroimaging substudy will also have PET/MR imaging performed at each visit. Neuroimaging activities will take place at Emory University in Atlanta, GA.

At the final visit (3-month follow-up), participants will also have blood tests to measure study drug concentration, as a measure of adherence to the assigned treatment.

Condition or DiseaseIntervention/Treatment
Hypertension, Resistant to Conventional Therapy
Drug: Minocycline HydrochlorideDrug: Placebo

Study Design

Study TypeInterventional
Actual Enrollment120 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingTriple
Primary PurposeTreatment
Official TitleAntihypertensive Mechanisms of Minocycline in Resistant Hypertension: Role of the Gut Microbiota-brain-immune Axis
Study Start DateJanuary 7, 2025
Actual Primary Completion Date2yrs 1mo from now
Actual Study Completion Date2yrs 1mo from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Minocycline Hydrochloride
Minocycline hydrochloride 100 mg, administered twice daily for 3 months
Drug: Minocycline Hydrochloride
Minocycline Hydrochloride 100 mg twice daily
Placebo
Placebo administered twice daily for 3 months
Drug: Placebo
Placebo

Outcome Measures

Primary Outcome Measures
  1. 24-h systolic blood pressure
    Change in mean 24-hour ambulatory systolic blood pressure
  2. Gut microbiome
    Change in butyrate-producing gene abundance
  3. Gut inflammation and leakiness
    Change in gut-homing inflammatory T-helper cells
  4. Neuroinflammation
    Change in \[18F\]FEPPA radiotracer uptake on PET/MR imaging
Secondary Outcome Measures
  1. Mucin-degrading gene abundance
    Change in mucin-degrading gene abundance
  2. IgA+ coated plasma cells
    Change in IgA+ coated plasma cells
  3. Gut leakiness markers
    Change in gut leakiness markers, including lipocalin-2, intestinal fatty-acid binding protein (I-FABP), zonulin, and lipopolysaccharides (LPS)
  4. 24-h diastolic blood pressure
    Change in mean 24-hour diastolic blood pressure
  5. 24-h heart rate
    Change in mean 24-hour heart rate
  6. Adverse Events
    Incidence of treatment-related adverse events

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
Age ≥18 years
Uncontrolled TRH, defined as uncontrolled blood pressure (mean 24-hour ambulatory systolic BP ≥125 mm Hg or diastolic BP ≥80 mm Hg) while being adherent to a stable (no changes in ≥14 days prior) antihypertensive regimen of 3 or more drugs, including an adequately dosed diuretic or unable to tolerate a diuretic.
The participant agrees to have all study procedures performed
Exclusion Criteria
Known hypersensitivity or contraindication to minocycline or other tetracyclines
Recent (≤3 months prior), ongoing, or expected use of oral antibiotics
Estimated glomerular filtration rate (eGFR) of \<45mL/min/1.73m2, using the MDRD equation
Known secondary hypertension
History of hypertensive crisis, defined as any in-patient hospitalizations for hypertensive crisis/emergency within the past year
History of orthostatic hypotension, defined as two or more episode(s) of orthostatic hypotension (reduction of SBP of \>20 mm Hg or DBP of \>10 mm Hg within 3 minutes of standing) in the past year
History of myocardial infarction, unstable angina, syncope, or cerebrovascular accident in prior 6 months
Evidence of alcoholism or drug abuse
Severe comorbid conditions (i.e., neoplasms or HIV positive or AIDS)
Current pregnancy or anticipated pregnancy during the study.

Contacts and Locations

Sponsors and CollaboratorsUniversity of Florida
Locations
UF Clinical Research Center (UF CRC) - CTSI | Gainesville Florida, United States, 32610
Investigators
Principal Investigator: Steven M Smith, PharmD, MPH, University of Florida