Mitigating the Pro-inflammatory Phenotype of Obesity (MAPLE)

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.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Diabetes; Insulin Resistance; Blood Pressure; Diuretics Drug Reactions; Sympathetic Nerve Activity
• Intervention / Treatment: Drug: Placebo; Drug: Clonidine Pill; Drug: Hydrochlorothiazide 12.5Mg Tab

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 Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Seth W Holwerda, Ph,D; Phone Number: 9729223230; Email: sholwerda@kumc.edu
• Study Contact Backup: Name: Davina A Clonch; Phone Number: 9132266009; Email: dclonch@kumc.edu

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66103
      • Recruiting
      • University of Kansas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: 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.	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.
EXPERIMENTAL: 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; Condition/disease indication(s): Vascular function and blood flow; Subject population: Hypertension; Dose(s): 0.1 mg (oral); Administration: Oral; Dosing regimen: 0.1 mg twice daily by mouth	Drug: Clonidine Pill; Will receive 4 week supply (35 days) of Clonidine Pills (0.1 mg twice/day) Planned use in this study; Condition/disease indication(s): Vascular function and blood flow; Subject population: Hypertension; Dose(s): 0.1 mg (oral); Administration: Oral; Dosing regimen: 0.1 mg twice daily by mouth; Other Names: Clonidine
EXPERIMENTAL: 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; Condition/disease indication(s): Hypertension; Subject population: Hypertension; Dose(s): 25 mg/day; Administration: Oral; Dosing regimen: 12.5 mg twice per day	Drug: 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; Condition/disease indication(s): Hypertension; Subject population: Hypertension; Dose(s): 25 mg/day; Administration: Oral; Dosing regimen: 12.5 mg twice per day; Other Names: Hydrochlorothiazide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2021
• Primary Completion (ANTICIPATED): July 31, 2025
• Study Completion (ANTICIPATED): July 31, 2025

Study Registration Dates

• First Submitted: March 31, 2021
• First Submitted That Met QC Criteria: June 17, 2021
• First Posted (ACTUAL): June 22, 2021

Study Record Updates

• Last Update Posted (ACTUAL): June 21, 2022
• Last Update Submitted That Met QC Criteria: June 15, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Glucose Metabolism Disorders; Metabolic Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Hyperinsulinism; Obesity; Insulin Resistance; Drug-Related Side Effects and Adverse Reactions; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sympatholytics; Sodium Chloride Symporter Inhibitors; Hydrochlorothiazide; Clonidine
• Other Study ID Numbers: 00147099

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No