Mitigating the Pro-inflammatory Phenotype of Obesity

NCT04934228 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 00147099
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (8)

• 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

  Difference in inflammatory markers in blood 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)

  Baseline

• 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

  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,

  Baseline

• 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

  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

  Baseline

• 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

  The difference in electrolytes blood test of participants in the Clonidine group compared with a BP-lowering control condition using hydrochlorothiazide (HCTZ) and a separate placebo treatment. • Blood Test: Electrolyte check by examining potassium concentration in blood. If potassium is 3.5 millimoles per liter or lower, oral 10 mg KCL will be prescribed to subject by a physician.

  1 Week

• 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

  The difference in electrolytes blood test of participants in the Clonidine group compared with a BP-lowering control condition using hydrochlorothiazide (HCTZ) and a separate placebo treatment. • Blood Test: Electrolyte check by examining potassium concentration in blood. If potassium is 3.5 millimoles per liter or lower, oral 10 mg KCL will be prescribed to subject by a physician.

  2 Week

• 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

  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)

  4 Week

• 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

  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,

  4 Week

• 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

  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

  4 Week

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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

Clonidine

EXPERIMENTAL

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

Hydrochlorothiazide (HCTZ)

EXPERIMENTAL

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

Interventions

Hydrochlorothiazide 12.5Mg Tab 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

Also known as: Hydrochlorothiazide

Hydrochlorothiazide (HCTZ)

Clonidine Pill 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

Also known as: Clonidine

Clonidine

Placebo 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.

Placebo

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Kansas Medical Center: lead

Study Sites (1)

University of Kansas Medical Center

Kansas City, Kansas, 66103, United States

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus; Obesity; Insulin Resistance

Interventions

Hydrochlorothiazide; Clonidine

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Imidazolines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Seth W. W Holwerda, PhD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Seth W Holwerda, Ph,D

CONTACT

9729223230; sholwerda@kumc.edu

Davina A Clonch

CONTACT

9132266009; dclonch@kumc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Mixed Model ANOVA 3-way analysis of variance to assess pain and BP responses to the clonidine, diuretic vs. placebo.

Study Record Dates

• First Submitted: March 31, 2021
• First Posted: June 22, 2021
• Study Start: July 1, 2021
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: June 5, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)