Study 1: Effect of Minocycline Treatment on Drug-Resistant Hypertensive Patients

• Status: Recruiting
• Trial end date: 2021-09-30
• Target enrollment: 0
• Participant gender: All

Summary

Hypertension (HTN) is the single most prevalent risk factor for cardiovascular disease, diabetes, obesity and metabolic syndrome. Recent American Heart Association (AHA) statistics indicate that one-third of all adults in the United States of America suffer from HTN. 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. A surgical approach such as the recently developed "Simplicity Catheter" assisted renal denervation remains one of the few options available to these patients. Thus, a mechanism-based breakthrough is imperative to develop novel strategies to prevent and perhaps eventually cure neurogenic hypertension (NH). This study is designed to evaluate a low and high dose of minocycline to test the hypothesis that minocycline treatment would produce antihypertensive effects in drug-resistant neurogenic hypertensive individuals. Minocycline has been selected because of its demonstrated effects on inhibiting microglial activation and its ability to penetrate the blood brain barrier. There is no other compound available that is safer and displays specificity better than Minocycline in inhibiting microglial activation. Thus, the potential therapeutic benefits of this inexpensive, well tolerated, already FDA-approved drug that has minimal side effects would be enormous.

• Phase: Phase 4
• 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

• Full-tolerated doses of 3 or more antihypertensive 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.

• The individual agrees to have all study procedures performed

• Willing to provide written consent

Exclusion

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

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

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

• Known hypersensitivity or contraindication to Minocycline or other tetracycline.

• Evidence of alcoholism or drug abuse;

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

• Women of childbearing potential