Study 3: Minocycline Decreases Microglia Activation

Study 3: Effect of Minocycline Treatment on Drug-Resistant Hypertensive Patients

This study is a mechanistic study that will enroll 9 subjects who are participating in NCT02133872 (which is designed to evaluate minocycline to test the hypothesis that minocycline treatment would produce antihypertensive effects in drug-resistant neurogenic hypertensive individuals) to test whether the antihypertensive effect of minocycline is associated with a decrease in activated microglia in central nervous system autonomic regions as evidenced by changes in PET and MRI imaging.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Minocycline

Detailed Description

This study (Study 3) will recruit 9 subjects from NCT02133872 (Study1) who will agree to undergo additional autonomic testing and imaging studies at baseline and after 6 months of study treatment. Specialized imaging of the brain using magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning will be conducted at the Montreal Neurological Institute, in Montreal Canada.

For this study (Study 3) we include participants being enrolled Study 1 and/or participants who have completed participation in Study 1 and have not taken minocycline for 2 months will be approached to enroll in Study 3.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • UF Health Cardiovascular Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria for Minocycline Subjects:

• Subjects participating in Study 1 will be eligible to participate.
• (For Study 3 Participants only) Willing to travel to Montreal, Canada for specialized imaging of the participant's brain using magnetic resonance imaging (MRI), positron emission tomography (PET) scanning, Autonomic Nervous System Testing and blood drawing- if participant qualifies

Exclusion Criteria for Minocycline Subjects:

-Female participants with positive pregnancy test.

Inclusion Criteria for Controls:

• No diagnosis of neurogenic (treatment-resistant) hypertension.
• Not treated with minocycline.
• Willing to travel to Montreal, Canada for brain imaging and testing.
• Able to provide informed consent.

Exclusion Criteria for Controls:

-Female participants with positive pregnancy test.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Minocycline Treatment Group; Participants with neurogenic treatment-resistant hypertension who meet inclusion/exclusion criteria will receive minocycline at a dose determined to be most effective in lowering blood pressure (based on results from Study 1). Participants will undergo brain imaging with MRI and PET at baseline and 26 weeks. Intervention: Drug: Minocycline Dose: 50, 100, or 200 mg/day (based on optimal BP-lowering dose from Study 1) Frequency: Administered orally twice daily (BID) Duration: 26 weeks	Drug: Minocycline; Subjects will receive the dose of Minocycline determined to best lower BP and will undergo baseline and 26 week follow-up MRI and PET scans for changes in the paraventricular nucleus.
No Intervention: Control; Patients without a diagnosis of neurogenic (treatment-resistant) Hypertension and have not been treated with minocycline will be recruited. These participants will undergo one-time brain imaging visit (MRI and PET)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PET Changes in the Paraventricular Nucleus From Baseline to 26 Weeks.	This outcome represents the change in PET signal intensity in the bilateral paraventricular nucleus before and after minocycline treatment. PET imaging was performed using the radiotracer [¹¹C]PBR28, which binds to the Translocator Protein (TSPO), a marker of activated microglia and neuroinflammation. To ensure accurate anatomical localization, each participant's PET scan was co-registered with a high-resolution T1-weighted MRI. Regions of interest (ROIs) were manually drawn on the MRI and applied to the PET images to extract PET signal from the same brain structures. The signal was quantified as non-displaceable binding potential (BP_ND). The change in signal is calculated as the average change in BP_ND at baseline minus the average change in BP_ND after treatment. A positive value indicates that the PET signal decreased following treatment, reflecting a reduction in microglial activation and suggesting a favorable anti-inflammatory response to minocycline.	Change in Baseline to 26 weeks

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Carl Pepine, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2016
• Primary Completion (Actual): November 1, 2018
• Study Completion (Actual): November 1, 2018

Study Registration Dates

• First Submitted: August 7, 2014
• First Submitted That Met QC Criteria: August 7, 2014
• First Posted (Estimated): August 11, 2014

Study Record Updates

• Last Update Posted (Estimated): July 1, 2025
• Last Update Submitted That Met QC Criteria: June 13, 2025
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Resistent Hypertension
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertension; Anti-Bacterial Agents; Anti-Infective Agents; Minocycline
• Other Study ID Numbers: IRB201500594 -N; R01HL132448 (U.S. NIH Grant/Contract); RO1HL3361028 (Other Identifier: NHLBI); 2013-00102 Study 3 (Other Identifier: Univeristy of Florida)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes