Study 2: Effect of Minocycline Treatment on Drug-Resistant Hypertensive Patients
| Status: | Recruiting |
|---|---|
| Conditions: | High Blood Pressure (Hypertension) |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 1/18/2019 |
| Start Date: | December 2016 |
| End Date: | May 2019 |
| Contact: | Dana Leach, DNP |
| Email: | leachdd@medicine.ufl.edu |
| Phone: | 352-273-8933 |
Angiotensin and Neuroimmune Activation in Hypertension
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.
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.
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.
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.
Inclusion:
- Greater than 18 and less than 80 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 weeks
prior to screening) that is expected to be maintained without changes for at least 6-9
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).
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