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.
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
5
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.
UF Health Cardiovascular Clinic
Gainesville, Florida, United States
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.
Time frame: Change in Baseline to 26 weeks
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