Study 2: Effect of Minocycline Treatment on Drug-Resistant Hypertensive Patients

• Status: Not yet recruiting
• Trial end date: 2023-05-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Florida
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Minocycline

Criteria

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

• eGFR of < 45 mL/min/1.73m2, using the MDRD calculation.

• More than one in-patient hospitalization for an anti-hypertensive crisis within the year.

• More than one episode(s) of orthostatic hypotension (reduction of SBP of ≥ 20 mmHg of diastolic blood pressure (DBP) of ≥ 10 mmHg within 3 minutes of standing).

• History of myocardial infarction (MI), unstable angina pectoris, syncope or a cardiovascular accident within 6 months of screening period

• Clinically significant atrioventricular (AV) conduction disturbances and/or arrhythmias (e.g. 2nd or 3rd degree AV block);

• Current of past history of heart failure (≤40% left ventricular ejection fraction (EF).

• Major of psychotropic agents and antidepressants.

• Use of nonsteroidal anti-inflammatory drug (NSAIDs)

• Known hypersensitivity or contraindication to Minocycline or other tetracycline.

• Smoking

• Concurrent severe disease (such as neoplasm or HIV positive or AIDS).