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

NCT02133872 | Completed Phase 2 Results

• 4 other identifiers: IRB2015005 -NRO1HL33610282013-00102 Study 11R01HL132448-01
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Resistent Hypertension

Outcome Measures

Primary Outcomes (1)

• Categorical Classification of Subjects Into Responders vs. Non-responders

  The primary measure of interest was the categorical classification of subjects into responders vs. non-responders upon treatment with a specific minocycline dose: 50, 100 or 200 mg/d. Responders are defined as subjects who achieve a drop of \>5 mmHg in mean daytime SBP, based on daytime ABPM measurements (7 am to 10 pm). For these participants, the discontinuation or lowering of the dose of a concurrent anti-hypertensive drug due to excessive SBP reduction will also be assessed. Excessive SBP reduction is defined as an office SBP \<120 mmHg or \>10 mmHg SBP decrease associated with symptom(s). On the other hand, non-responders are defined as the participants that fail to show any change in their average daytime SBP measured through ABPM despite being exposed to the different minocycline doses evaluated.

  180 days

Secondary Outcomes (2)

• Change in 24 Hour SBP by ABPM

  180 days

• Changes in Office SBP Over Time

  180 days

Study Arms (3)

Minocycline (50 mg/d)

EXPERIMENTAL

Subjects received minocycline 50mg/d.

Drug: Minocycline 50mg/d

Minocycline (100 mg/d)

EXPERIMENTAL

Subjects received minocycline 50mg escalating to 100 mg/d.

Drug: Minocycline 100mg/d

Minocycline (200 mg/d)

EXPERIMENTAL

Subjects received minocycline 50mg escalating to 100 mg then 200 mg/d.

Device: Minocycline 200mg/d

Interventions

Minocycline 50mg/d DRUG

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.

Minocycline (50 mg/d)

Minocycline 100mg/d DRUG

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.

Minocycline (100 mg/d)

Minocycline 200mg/d DEVICE

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.

Minocycline (200 mg/d)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Florida: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

UF Health Cardiovascular Clinic

Gainesville, Florida, 32610, United States

Location

MeSH Terms

Conditions

Hypertension

Interventions

Minocycline

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Carl J. Pepine
• Organization: University of Florida

carl.pepine@medicine.ufl.edu

(352) 339-0696

Study Officials

• Carl Pepine, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open label, dose effectiveness trial

Study Record Dates

• First Submitted: May 6, 2014
• First Posted: May 8, 2014
• Study Start: October 1, 2014
• Primary Completion: November 1, 2018
• Study Completion: November 1, 2018
• Last Updated: October 23, 2025
• Results First Posted: October 23, 2025

Record last verified: 2025-10

Locations

US (1)