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

NCT ID: NCT02133885

Last Updated: 2024-02-01

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-30
• Study Completion Date: 2024-03-31

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.

Detailed Description

This is a double-blind, placebo-controlled, cross over design to evaluate the effects of minocycline in patients with resistent hypertension. After providing informed consent, patients will have baseline and followup visits during which a brief physical examination will be performed, medical history, assessment of medication compliance and tolerance, and vital signs will be completed.

Subjects will undergo blood (lipid panel, high sensitivity-C reactive protein, high sensitivity troponin, glucose, metabolic profile, lipid panel, Cystatin C and albumin) and urine studies at the baseline visit and at 16, 19, 35 and 54 weeks. Patients will have ambulatory BP monitoring at baseline and at the end of each treatment period.

Patients will be randomized to drug scheme A or B. One scheme will follow the following order: 16 weeks of minocycline, followed by a 3 week wash out period, then 16 weeks of placebo, then 3 weeks of wash out and a final 16 week period of minocycline. The other scheme will consist of 16 weeks of placebo, followed by 3 week wash out period, followed by 16 weeks of minocycline, then 3 week wash out and a final 16 weeks of placebo. Study visits will occur at study entry (baseline/randomization), 16 weeks, 19 weeks, 35 weeks, 38 weeks, and 54 weeks for each group. Patient participation will end after 56 weeks.

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Minocycline Group

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.

Group Type: ACTIVE_COMPARATOR

Minocycline Group

Intervention Type: 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.

Placebo Group

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.

Group Type: PLACEBO_COMPARATOR

Placebo Group

Intervention Type: 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.

Interventions

Minocycline Group

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.

Intervention Type: DRUG

Placebo Group

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carl Pepine, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

UF Health Cardiovascular Clinic

Gainesville, Florida, United States

Countries

United States

Other Identifiers

RO1HL3361028

Identifier Type: OTHER

Identifier Source: secondary_id

2013-00102 Study 2

Identifier Type: OTHER

Identifier Source: secondary_id

R01HL132448-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB201500594-N

Identifier Type: -

Identifier Source: org_study_id