Hypertension
Conditions
Keywords
Resistent Hypertension
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.
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.
Interventions
DRUGMinocycline
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.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of Florida
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PET Changes in the Paraventricular Nucleus From Baseline to 26 Weeks. | Change in 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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
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. | 5 |
| 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) | 0 |
| Total | 5 |
Baseline characteristics
| Characteristic | Minocycline Treatment Group | Total |
|---|---|---|
| Age, Continuous | 69.20 Years STANDARD_DEVIATION 3.7 | 69.20 Years STANDARD_DEVIATION 3.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants |
| Region of Enrollment United States | 5 participants | 5 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 0 |
| other Total, other adverse events | 0 / 5 | 0 / 0 |
| serious Total, serious adverse events | 0 / 5 | 0 / 0 |
Outcome results
Primary
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
Population: One subject was identified as a slow metabolizer of \[¹¹C\]PBR28 and therefore their data could not be used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline Treatment Group | PET Changes in the Paraventricular Nucleus From Baseline to 26 Weeks. | 0.0350 Binding Potential (non-displaceable) | Standard Deviation 0.0292 |