Clinical trial NCT04934228: Mitigating the Pro-inflammatory Phenotype of Obesity
Official title: Mitigating the Pro-inflammatory Phenotype of Obesity
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Blood Pressure
Diabetes
Obesity
Insulin Resistance
Diuretics Drug Reactions
Sympathetic Nerve Activity
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
First posted: 2021-06-22
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

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

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Baseline
measure: 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
timeFrame: Baseline
measure: 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
timeFrame: Baseline
measure: 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
timeFrame: 1 Week
measure: 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
timeFrame: 2 Week
measure: 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
timeFrame: 4 Week
measure: 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
timeFrame: 4 Week
measure: 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
timeFrame: 4 Week
Secondary outcomes:
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
Study officials:
affiliation: University of Kansas Medical Center
name: Seth W. W Holwerda, PhD
role: PRINCIPAL_INVESTIGATOR
References: