Mitigating the Pro-inflammatory Phenotype of Obesity

NCT ID: NCT04934228

Last Updated: 2025-06-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-01
• Study Completion Date: 2027-08-01

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

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Will receive a 4 week supply (35 days) of Placebo Pills; has no active ingredients but is made to look like the study drug.

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

Group Type: EXPERIMENTAL

Clonidine Pill

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Hydrochlorothiazide 12.5Mg Tab

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Hydrochlorothiazide; Clonidine

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Kansas Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Seth Holwerda PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Seth W. W Holwerda, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Kansas Medical Center

Locations

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Seth W Holwerda, Ph,D

Role: CONTACT

sholwerda@kumc.edu

9729223230

Davina A Clonch

Role: CONTACT

dclonch@kumc.edu

9132266009

Facility Contacts

Seth W. W Holwerda

Role: primary

sholwerda@kumc.edu

9729223230

Other Identifiers

00147099

Identifier Type: -

Identifier Source: org_study_id