Blood Pressure, Diabetes, Diuretics Drug Reactions, Insulin Resistance, Obesity, Sympathetic Nerve Activity
Conditions
Brief summary
The purpose of this study is to examine the hypothesize that 4 weeks of sympathetic nerve activity (SNA) inhibition (oral clonidine) will cause a significant reduction in circulating blood concentrations and endothelial cell expression of inflammatory markers (e.g., TNF-α, IL-6). Our study is a prospective study using a randomized, double-blinded design to test 4 weeks of SNA blockade (oral clonidine) compared with a BP-lowering control condition (diuretic, hydrochlorothiazide) or a placebo.
Detailed description
1. Using a randomized, double-blinded, parallel-design approach, we hypothesize that 4 weeks of SNA blockade (oral clonidine) will cause a significant reduction in expression of inflammatory markers in blood, endothelial cells, and central adipose compared with a BP-lowering control condition using hydrochlorothiazide (HCTZ) and a separate placebo treatment. 2. Determine the extent to which inflammation in the body is caused by elevated sympathetic nerve activity
Interventions
DRUGHydrochlorothiazide 12.5Mg Tab
Will receive 4 week supply (35 days) of Hydrochlorothiazide Pills (12.5 mg twice a day) Planned use in this study 1. Condition/disease indication(s): Hypertension 2. Subject population: Hypertension 3. Dose(s): 25 mg/day 4. Administration: Oral 5. Dosing regimen: 12.5 mg twice per day
DRUGClonidine Pill
Will receive 4 week supply (35 days) of Clonidine Pills (0.1 mg twice/day) Planned use in this study 1. Condition/disease indication(s): Vascular function and blood flow 2. Subject population: Hypertension 3. Dose(s): 0.1 mg (oral) 4. Administration: Oral 5. Dosing regimen: 0.1 mg twice daily by mouth
DRUGPlacebo
Will receive a 4 week supply (35 days) of Placebo Pills; has no active ingredients but is made to look like the study drug.
Sponsors
University of Kansas Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Masking description
Randomized, double-blinded, parallel-design approach. Randomization to either the clonidine, diuretic vs. placebo will occur determined/generated by computer generated randomization and stratified by age and sex to balance the three groups.
Intervention model description
Mixed Model ANOVA 3-way analysis of variance to assess pain and BP responses to the clonidine, diuretic vs. placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Male or Female, age 18-79 * Obese: BMI \> 30 m/kg2 * Hypertensive: blood pressure \>130/80 * Elevated insulin resistance (HOMA-IR \> 2.5) * Waist circ: \>102 cm (men) and \>88 cm (women) * Fasting glucose \< 126 mg/dL * Fasting triglycerides \< 250 mg/dL * HbA1c \< 6.5% * Willing to visit research lab (Fairway CTSU) * Willing to undergo a blood draw * Able to provide written informed consent
Exclusion criteria
* Current use of clonidine or beta-blockers * Current smoker or History of smoking in the past 3 months. * Hyperlipidemia: Fasting triglycerides \> 250 mg/dL * Currently taking hypertension medication * History of heart disease (e.g., myocardial infarction, stent, byass, heart attack, stroke, heart failure, valvular heart disease, cardiomyopathy) * History of neurological disorders * History of transplant * Actively participating in other studies, except for a registry study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood Work: Efficacy of 4-week supply of Clonidine Compared VS 4-week supply of control condition using hydrochlorothiazide (HCTZ) and a separate placebo treatment | Baseline | Difference in inflammatory markers in blood compared with a BP-lowering control condition using hydrochlorothiazide (HCTZ) and a separate placebo treatment * Norepinephrine (inflammation) Blood Test: pg/mL normal range for norepinephrine is 70 to 1700 pg/mL * Tumor necrosis factor-alpha (TNF-α) and interlukin-6 (IL6) Blood Test: pg/mL normal values: IL-6 was 6-31 pg/mL and TNF-α 5 pg/mL, * Nitrotyrosine (Oxidative stress) |
| Endothelial Cell Sample: Efficacy of 4-week supply of Clonidine Compared VS 4-week supply of control condition using hydrochlorothiazide (HCTZ) and a separate placebo treatment | Baseline | Difference in endothelial cells samples compared with a BP-lowering control condition using hydrochlorothiazide (HCTZ) and a separate placebo treatment Endothelial cell tissue will be assessed by the KU Histology Core for markers of inflammation and oxidative stress independently from the PI's lab, |
| Adipose Tissue Sample: Efficacy of 4-week supply of Clonidine Compared VS 4-week supply of control condition using hydrochlorothiazide (HCTZ) and a separate placebo treatment | Baseline | Difference in central adipose compared with a BP-lowering control condition using hydrochlorothiazide (HCTZ) and a separate placebo treatment Adipose tissue are expected following 4 weeks of clonidine but not HCTZ or placebo |
Countries
United States
Contacts
Primary ContactSeth W Holwerda, Ph,D
Backup ContactDavina A Clonch
Outcome results
None listed