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RecruitingNCT06246396Updated Mar 6, 2026

Antihypertensive Mechanisms of Minocycline in Resistant Hypertension

A Phase 4 interventional study of Minocycline Hydrochloride and Placebo in Hypertension, Resistant to Conventional Therapy, sponsored by University of Florida. Recruiting at 1 site in United States. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2026-03-06.

Sponsored by University of Florida · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
120
Allocation
Randomized
Ages
18 Years to 100 Years
Sex
All
01

Study summary

The goal of this clinical trial is to learn about the mechanisms by which minocycline effect blood pressure in individuals with treatment-resistant hypertension. The main questions it aims to answer are:

  • To what extent does minocycline lower blood pressure?
  • Are such blood pressure effects mediated through changes in gut microbiota, gut leakiness, systemic inflammation, neuroinflammation, or some combination of these?

Participants will be randomly assigned to treatment with minocycline or placebo, treated daily for 3 months, to evaluate these questions.

Read the detailed 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.

02

Conditions studied

  • Hypertension, Resistant to Conventional Therapy

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Keywords

  • minocycline
  • blood pressure
03

Who can participate

Ages eligible
18 Years to 100 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
120 participants (estimated)

Study arms

  • Experimental
    Minocycline Hydrochloride

    Minocycline hydrochloride 100 mg, administered twice daily for 3 months

    Drug: Minocycline Hydrochloride

  • Placebo comparator
    Placebo

    Placebo administered twice daily for 3 months

    Drug: Placebo

Interventions

  • DrugMinocycline Hydrochloride

    Minocycline Hydrochloride 100 mg twice daily

    Also known as: Minocycline, Minocin

  • DrugPlacebo

    Placebo

05

What researchers measure

Primary outcomes

  1. 24-h systolic blood pressure

    Change in mean 24-hour ambulatory systolic blood pressure

    Time frame: 3 months

  2. Gut microbiome

    Change in butyrate-producing gene abundance

    Time frame: 3 months

  3. Gut inflammation and leakiness

    Change in gut-homing inflammatory T-helper cells

    Time frame: 3 months

  4. Neuroinflammation

    Change in \[18F\]FEPPA radiotracer uptake on PET/MR imaging

    Time frame: 3 months

Secondary outcomes

  1. Mucin-degrading gene abundance

    Change in mucin-degrading gene abundance

    Time frame: 3 months

  2. IgA+ coated plasma cells

    Change in IgA+ coated plasma cells

    Time frame: 3 months

  3. Gut leakiness markers

    Change in gut leakiness markers, including lipocalin-2, intestinal fatty-acid binding protein (I-FABP), zonulin, and lipopolysaccharides (LPS)

    Time frame: 3 months

  4. 24-h diastolic blood pressure

    Change in mean 24-hour diastolic blood pressure

    Time frame: 3 months

  5. 24-h heart rate

    Change in mean 24-hour heart rate

    Time frame: 3 months

  6. Adverse Events

    Incidence of treatment-related adverse events

    Time frame: 3 months

06

Study locations

1 of 1 sites recruiting
  • UF Clinical Research Center (UF CRC) - CTSI
    Gainesville, Florida 32610, United States
    Recruiting
07

Registry details

Key details

Study ID
NCT06246396
Lead sponsor
University of Florida
Collaborators
Emory University, National Heart, Lung, and Blood Institute (NHLBI)
Responsible party
Sponsor
First posted
Feb 7, 2024
Start date
Jan 8, 2025
Primary completion
Jul 2028 (estimated)
Completion
Jul 2028 (estimated)
Last update
Mar 6, 2026

Study contacts

Joshua N Terrell
Contact
jterrell5102@ufl.edu
352-294-8297
David B Smith
Contact
dbsmith@cop.ufl.edu
352-294-8297
Steven M Smith, PharmD, MPH
principal investigator · University of Florida

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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