Sympathetic Regulation of Large Artery Stiffness in Humans With ISH

Study Overview
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Brief Summary
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Stiffening of your blood vessels, particularly the large vessels from your heart (called the aorta and carotids) you age contributes to the development of cardiovascular disease (CVD) such as heart attack and stroke. Nerve activity from your brain to your body also increases with advancing age but it is unknown if this nerve activity contributes directly to the stiffening on your blood vessels in older adults in addition to high blood pressure. Therefore, successful completion of the proposed aims will have a significant clinical impact by identifying if nerve activity from your brain could be a novel target for therapies that would lower stiffness of the aorta and carotid arteries in older adults.

Official Title
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Sympathetic Regulation of Large Artery Stiffness in Humans With Age-Related Isolated Systolic Hypertension

Conditions
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Hypertension, Systolic, Stiffness, Aortic

Intervention / Treatment
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* Drug: Clonidine
* Drug: Hydrochlorothiazide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 60-85 non-smoking clinically healthy untreated or treated stage 1 isolated systolic hypertension (ISH) (systolic BP 130-139 mmHg; diastolic BP <90 mmHg) or stage 2 ISH (systolic BP 140-159 mmHg; diastolic BP <90 mmHg) per 2017 AHA/ACC hypertension guidelines if subject is on antihypertensive medications, they will stop taking medication for a one-week washout period after Visit 1 before they return for Visit 2. They will come in at day 3 and day 7 of the one-week washout for a BP reading, to confirm that systolic BP is <160 mmHg. Exclusion Criteria: no history of cardiovascular disease (e.g., myocardial infarction, bypass surgery, angioplasty/stent, heart failure, cardiomyopathy, pacemaker/defibrillator, peripheral artery disease), pulmonary disease, liver disease, Type I or II diabetes, cancer (treated by chemotherapy and/or radiation), psychiatric illness, on aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs). aspirin, NSAIDs, vitamins, herbal supplements, omega-3-fatty acids will have to discontinue for at least 1 week before participation and remain discontinued during the study. blood thinners, serotonin reuptake inhibitors (SSRIs), or PDE5 inhibitors will also be excluded. Women must be postmenopausal for at least 6 months (surgical or natural) and not currently on hormone replacement therapy. Subjects not on antihypertensive will not be eligible if their resting clinic systolic BP is <130 mmHg or >160 mmHg and diastolic BP >90 mmHg.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, placebo controlled, parallel design
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clonidine<br>0.2 mg/day oral | Drug: Clonidine<br>* Clonidine 0.2 mg/day oral tablet<br>|
| Active Comparator: Hydrochlorothiazide<br>37.5 mg/day oral | Drug: Hydrochlorothiazide<br>* Hydrochlorothiazide 37.5 mg/day oral tablet<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in carotid-femoral pulse wave velocity | Aortic stiffness | Baseline and after 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in carotid distensibility index | Change in carotid distensibility | Baseline and after 4 weeks | 
| Change in carotid flow pulsatility index | Change in carotid flow pulsatility | Baseline and after 4 weeks | 
| Change in carotid intimal medial thickness (IMT) | Change in carotid wall thickness | Baseline and after 4 weeks |