Mitigating the Pro-inflammatory Phenotype of Obesity (MAPLE)

University of Kansas

Status and phase: Enrolling; Phase 1

Conditions: Diabetes; Sympathetic Nerve Activity; Diuretics Drug Reactions; Insulin Resistance; Obesity; Blood Pressure

Treatments: Drug: Placebo; Drug: Clonidine Pill; Drug: Hydrochlorothiazide 12.5Mg Tab

Study type: Interventional

Funder types: Other

Identifiers

NCT04934228

00147099

Details and patient eligibility

About

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.

Full 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

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 79 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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60 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Clonidine

Experimental group

Description:

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

Treatment:

Drug: Clonidine Pill

Hydrochlorothiazide (HCTZ)

Experimental group

Description:

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

Treatment:

Drug: Hydrochlorothiazide 12.5Mg Tab