Mitigating the Pro-inflammatory Phenotype of Obesity

Purpose

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.

Conditions

  • Blood Pressure
  • Diabetes
  • Obesity
  • Insulin Resistance
  • Diuretics Drug Reactions
  • Sympathetic Nerve Activity

Eligibility

Eligible Ages
Between 18 Years and 79 Years
Eligible Genders
All
Accepts 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.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Mixed Model ANOVA 3-way analysis of variance to assess pain and BP responses to the clonidine, diuretic vs. placebo.
Primary Purpose
Other
Masking
Double (Participant, 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.

Arm Groups

ArmDescriptionAssigned Intervention
Placebo Comparator
Placebo 		KU Investigational Pharmacy will provide the drug prescription bottle with 35-day supply of placebo to the research coordinator to give to the research participant. The placebo is an inert substance with no intended medical value and is used as a negative control for comparison with the study drug. Participants will receive a Placebo Pill; has no active ingredients but is made to look like the study drug.
  • Drug: Placebo
    Will receive a 4 week supply (35 days) of Placebo Pills; has no active ingredients but is made to look like the study drug.
Experimental
Clonidine 		KU Investigational Pharmacy will provide the drug prescription bottle with 35-day supply of clonidine to the research coordinator to give to the research participant. 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
  • Drug: Clonidine 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
    Other names:
    • Clonidine
Experimental
Hydrochlorothiazide (HCTZ) 		KU Investigational Pharmacy will provide the drug prescription bottle with 35-day supply of Hydrochlorothiazide to the research coordinator to give to the research participant. 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
  • Drug: Hydrochlorothiazide 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
    Other names:
    • Hydrochlorothiazide

Recruiting Locations

University of Kansas Medical Center
Kansas City, Kansas 66103
Contact:
Seth W. W Holwerda
972-922-3230
sholwerda@kumc.edu

More Details

Status
Recruiting
Sponsor
University of Kansas Medical Center

Study Contact

Seth W Holwerda, Ph,D
9729223230
sholwerda@kumc.edu

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