Mitigating the Pro-inflammatory Phenotype of Obesity

Phase 1

Recruiting

• Conditions: Blood Pressure; Insulin Resistance; Diabetes; Diuretics Drug Reactions; Sympathetic Nerve Activity; Obesity
• Interventions: Drug: Placebo; Drug: Clonidine Pill; Drug: Hydrochlorothiazide 12.5Mg Tab

• Registration Number: NCT04934228
• Lead Sponsor: University of Kansas Medical Center

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

Study Timeline

• Study First Submitted: 2021-03-31
• Study First Submitted QC: 2021-06-17
• Study First Posted: 2021-06-22
• Study Start: 2021-07-01
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-04
• Last Update Posted: 2024-10-08
• Primary Completion: 2025-07-31
• Study Completion: 2025-07-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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.
Clonidine	Clonidine Pill	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
Hydrochlorothiazide (HCTZ)	Hydrochlorothiazide 12.5Mg Tab	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

Primary Outcome Measures

Name	Time	Method
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	4 Week	Difference in inflammatory markers in blood, endothelial cells, and central adipose 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	4 Week	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	4 Week	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

Trial Locations

Locations (1)

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States