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

NCT02133885 | Withdrawn Phase 1 FDA Drug

• 4 other identifiers: IRB201500594-NRO1HL33610282013-00102 Study 2R01HL132448-01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hypertension

Keywords

Resistent Hypertension; Systolic Blood Pressure

Outcome Measures

Primary Outcomes (1)

• Reduction of ambulatory blood pressure

  Change in systolic blood pressure.

  Change in baseline to week 54

Study Arms (2)

Minocycline Group

ACTIVE COMPARATOR

These subjects will start with minocycline for 16 weeks, followed by a washout period for 3 weeks, then will receive a placebo for 16 weeks, followed by a washout period for 3 weeks, then will finish with minocycline for 16 weeks.

Drug: Minocycline Group

Placebo Group

PLACEBO COMPARATOR

These subjects will start with placebo (this will look like minocycline) for 16 weeks, followed by a washout period for 3 weeks, then will receive a minocycline for 16 weeks, followed by a washout period for 3 weeks, then will finish with placebo for 16 weeks.

Other: Placebo Group

Interventions

Minocycline Group DRUG

These subjects will start with minocycline for 16 weeks, followed by a washout period for 3 weeks, then will receive a placebo for 16 weeks, followed by a washout period for 3 weeks, then will finish with minocycline for 16 weeks.

Minocycline Group

Placebo Group OTHER

These subjects will start with placebo (tablet looking just like minocycline) for 16 weeks, followed by a washout period for 3 weeks, then will receive minocycline for 16 weeks, followed by a washout period for 3 weeks, then will finish with placebo for 16 weeks.

Placebo Group

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
• 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.

You may not qualify if:

• 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).

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

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• Carl Pepine, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2014
• First Posted: May 8, 2014
• Study Start: January 30, 2023
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2024
• Last Updated: February 1, 2024

Record last verified: 2024-01

Locations

US (1)