Study 3: Minocycline Decreases Microglia Activation

NCT02213575 | Completed Phase 2 Results FDA Drug

• 4 other identifiers: IRB201500594 -NRO1HL33610282013-00102 Study 3R01HL132448
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypertension

Keywords

Resistent Hypertension

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Minocycline Treatment Group

EXPERIMENTAL

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

Control

NO INTERVENTION

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)

Interventions

Minocycline DRUG

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.

Minocycline Treatment Group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Female participants with positive pregnancy test.
• 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.
• Female participants with positive pregnancy test.

Sponsors & Collaborators

• University of Florida: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

UF Health Cardiovascular Clinic

Gainesville, Florida, 32610, United States

Location

MeSH Terms

Conditions

Hypertension

Interventions

Minocycline

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Carl J. Pepine
• Organization: University of Florida

carl.pepine@medicine.ufl.edu

(352) 339-0696

Study Officials

• Carl Pepine, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2014
• First Posted: August 11, 2014
• Study Start: March 5, 2016
• Primary Completion: November 1, 2018
• Study Completion: November 1, 2018
• Last Updated: July 1, 2025
• Results First Posted: July 1, 2025

Record last verified: 2023-05

Locations

US (1)