Hypertension, Resistant to Conventional TherapyPhase 4NCT06246396
Antihypertensive Mechanisms of Minocycline in Resistant Hypertension
A Phase 4 study testing Minocycline Hydrochloride in people with Hypertension, Resistant to Conventional Therapy, run by University of Florida at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Hypertension, Resistant to Conventional Therapy
- What is being tested?
- Minocycline Hydrochloride
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jan 2025to Jul 2028
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UF Clinical Research Center (UF CRC) - CTSI
Gainesville, Florida, 32610
Joshua N Terrell, 352-294-8297, jterrell5102@ufl.edu
David B Smith, 352-294-8297, dbsmith@cop.ufl.edu
About this study
Official title: Antihypertensive Mechanisms of Minocycline in Resistant Hypertension: Role of the Gut Microbiota-brain-immune Axis
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.
- Being tested
- Minocycline Hydrochloride, Placebo
- Keywords
- minocycline, blood pressure
- Medical subject headings
- Hypertension Resistant to Conventional Therapy, cyclopia sequence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Minocycline HydrochlorideDrug
Also called Minocycline, Minocin
Minocycline Hydrochloride 100 mg twice daily
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Minocycline Hydrochloride | Experimental | Minocycline hydrochloride 100 mg, administered twice daily for 3 months Receives: Drug: Minocycline Hydrochloride |
| Placebo | Placebo comparator | Placebo administered twice daily for 3 months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
24-h systolic blood pressure
Change in mean 24-hour ambulatory systolic blood pressure
Measured: 3 months
Gut microbiome
Change in butyrate-producing gene abundance
Measured: 3 months
Gut inflammation and leakiness
Change in gut-homing inflammatory T-helper cells
Measured: 3 months
Neuroinflammation
Change in [18F]FEPPA radiotracer uptake on PET/MR imaging
Measured: 3 months
Secondary outcomes (6)
Mucin-degrading gene abundance
Change in mucin-degrading gene abundance
Measured: 3 months
IgA+ coated plasma cells
Change in IgA+ coated plasma cells
Measured: 3 months
Gut leakiness markers
Change in gut leakiness markers, including lipocalin-2, intestinal fatty-acid binding protein (I-FABP), zonulin, and lipopolysaccharides (LPS)
Measured: 3 months
24-h diastolic blood pressure
Change in mean 24-hour diastolic blood pressure
Measured: 3 months
24-h heart rate
Change in mean 24-hour heart rate
Measured: 3 months
Adverse Events
Incidence of treatment-related adverse events
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2024
- Study start8 Jan 2025
- Primary completionJul 2028 (estimated)
- Study completionJul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypertension, Resistant to Conventional TherapyStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Steven M Smith, PharmD, MPH, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06246396
- Sponsor's protocol ID
- IRB202301939
- Other IDs
- 2R01HL132448-05A1
- Status last verified
- Mar 2026
- First submitted
- 30 Jan 2024
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No