Angiotensin and Neuroimmune Activation in Hypertension
Angiotensin and Neuroimmune Activation in Hypertension
Hypertension (HTN) is the single most prevalent risk factor for cardiovascular disease, diabetes, obesity and metabolic syndrome. Despite advances in life style modification and multi-drug therapies, 20-30% of all hypertensive patients remain resistant.
These individuals exhibit autonomic dysregulation due to elevated sympathetic activity and norepinephrine spillover, and low parasympathetic activity. It is generally accepted that this uncontrolled, resistant HTN is primarily "neurogenic" in origin, involving over activity of the sympathetic nervous system that initiates and sustains HTN. Thus, a mechanism-based breakthrough is imperative to develop novel strategies to prevent and perhaps eventually cure neurogenic hypertension (NH).
This study is a double-blind, placebo-controlled, cross-over design to test the hypothesis that minocycline treatment would produce antihypertensive effects in drug-resistant neurogenic hypertensive individuals.
This is a double-blind, placebo-controlled, cross over design to evaluate the effects of minocycline in patients with resistent hypertension. After providing informed consent, patients will have baseline and followup visits during which a brief physical examination will be performed, medical history, assessment of medication compliance and tolerance, and vital signs will be completed.
Subjects will undergo blood (lipid panel, high sensitivity-C reactive protein, high sensitivity troponin, glucose, metabolic profile, lipid panel, Cystatin C and albumin) and urine studies at the baseline visit and at 16, 19, 35 and 54 weeks. Patients will have ambulatory BP monitoring at baseline and at the end of each treatment period.
Patients will be randomized to drug scheme A or B. One scheme will follow the following order: 16 weeks of minocycline, followed by a 3 week wash out period, then 16 weeks of placebo, then 3 weeks of wash out and a final 16 week period of minocycline. The other scheme will consist of 16 weeks of placebo, followed by 3 week wash out period, followed by 16 weeks of minocycline, then 3 week wash out and a final 16 weeks of placebo. Study visits will occur at study entry (baseline/randomization), 16 weeks, 19 weeks, 35 weeks, 38 weeks, and 54 weeks for each group. Patient participation will end after 56 weeks.
Inclusion:
Greater than 18 and less than 86 years of age;
On stable medication regimen
o Full-tolerated doses of 3 or more anti-hypertensive medications of different classes, one of which must be a diuretic (with no changes for a minimum of two months prior to screening) that is expected to be maintained without changes for at least 3 months.
Office systolic blood pressure (SBP) of greater than 160 mmHg based on an average of 3 blood pressure readings measured at both initial screening visit
The individual agrees to have all study procedures performed
Willing to provide written consent
Females with childbearing potential must not be pregnant.
Exclusion