Study 3: Minocycline Decreases Microglia Activation

Study Overview
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Brief Summary
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This study is a mechanistic study that will enroll 9 subjects who are participating in NCT02133885 (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
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This study will recruit 9 subjects from NCT02133885 who will agree to undergo additional autonomic testing and imaging studies at baseline and after 3-6 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.

Official Title
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Effect of Minocycline Treatment on Drug-Resistant Hypertensive Patients

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Minocycline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects participating in IRB approved protocol #102-2013 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 control and resistant hypertensive subjects include: currently pregnant or have been pregnant in the last 6 months; antibiotic treatment within 2 months of study enrollment; currently taking a medication (e.g., antibiotic, anti-inflammatory agents, glucocorticoids or other immune modulating medications); unwilling to discontinue vitamin or supplements, including probiotics, potentially affecting gut microbiota (vitamins/supplements and medications that possibly affect the gut microbiota should be discontinued for at least 2wks prior to stool collection); history of intestinal surgery, inflammatory bowel disease, celiac disease, lactose intolerance, chronic pancreatitis or other malabsorption disorder.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Minocycline<br>Subjects will receive the dose of Minocycline determined to best lower BP and will undergo baseline and week 12-24 follow-up MRI and PET scans for changes in the paraventricular nucleus. | Drug: Minocycline<br>* Subjects will receive the dose of Minocycline determined to best lower BP and will undergo baseline and week 12-24 follow-up MRI and PET scans for changes in the paraventricular nucleus.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI changes in the paraventricular nucleus | MRI changes in the paraventricular nucleus from baseline to 12 weeks. Increased binding in the autonomic brain regions (paraventricular nucleus) | Change from baseline to 12 weeks | 
| MRI changes in the paraventricular nucleus | MRI changes in the paraventricular nucleus from baseline to 24 weeks. Increased binding in the autonomic brain regions (paraventricular nucleus) | Change in Baseline to 24 weeks | 
| PET changes in the paraventricular nucleus | PET changes in the paraventricular nucleus from baseline to 12 weeks. Increased binding in the autonomic brain regions (paraventricular nucleus) | Change from baseline to 12 weeks | 
| PET changes in the paraventricular nucleus | PET changes in the paraventricular nucleus from baseline to 24 weeks. Increased binding in the autonomic brain regions (paraventricular nucleus) | Change in Baseline to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Resistent Hypertension