Antihypertensive Mechanisms of Minocycline in Resistant Hypertension

NCT ID: NCT06246396

Last Updated: 2026-01-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-08
• Study Completion Date: 2028-07-31

Brief 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.

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.

Conditions

Hypertension, Resistant to Conventional Therapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Minocycline Hydrochloride

Minocycline hydrochloride 100 mg, administered twice daily for 3 months

Group Type: EXPERIMENTAL

Minocycline Hydrochloride

Intervention Type: DRUG

Minocycline Hydrochloride 100 mg twice daily

Placebo

Placebo administered twice daily for 3 months

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Minocycline Hydrochloride

Minocycline Hydrochloride 100 mg twice daily

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

Minocycline; Minocin

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Emory University

OTHER

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven M Smith, PharmD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

UF Clinical Research Center (UF CRC) - CTSI

Gainesville, Florida, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Joshua N Terrell

Role: CONTACT

jterrell5102@ufl.edu

352-294-8297

David B Smith

Role: CONTACT

dbsmith@cop.ufl.edu

352-294-8297

Facility Contacts

Joshua N Terrell

Role: primary

jterrell5102@ufl.edu

352-294-8297

David B Smith

Role: backup

dbsmith@cop.ufl.edu

352-294-8297

Other Identifiers

2R01HL132448-05A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB202301939

Identifier Type: -

Identifier Source: org_study_id