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

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.

Conditions

• Hypertension

Interventions

DRUG

Minocycline 50mg/d

Subjects will receive minocycline 50mg if no mean daytime ABPM SBP decline =/\> 5mm Hg; subjects will receive minocycline 100mg, if no mean daytime ABPM SBP decline =/\> 5mm Hg BP subjects will receive minocycline 200 mg.

DRUG

Minocycline 100mg/d

Subjects will receive minocycline 50mg if no mean daytime ABPM SBP decline =/\> 5mm Hg; subjects will receive minocycline 100mg, if no mean daytime ABPM SBP decline =/\> 5mm Hg BP subjects will receive minocycline 200 mg.

DEVICE

Minocycline 200mg/d

Subjects will receive minocycline 50mg if no mean daytime ABPM SBP decline =/\> 5mm Hg; subjects will receive minocycline 100mg, if no mean daytime ABPM SBP decline =/\> 5mm Hg BP subjects will receive minocycline 200 mg.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)

  collaborator NIH

• University of Florida

  lead OTHER

Principal Investigators

• Carl Pepine, MD · University of Florida

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-10-31

Primary Completion

2018-11-01

Completion

2018-11-01

Countries

• United States

Study Locations