Mitigating the Pro-inflammatory Phenotype of Obesity

Obesity Clinical Trial

— MAPLE  

Official title:

Mitigating the Pro-inflammatory Phenotype of Obesity

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04934228
• Other study ID #: 00147099
• Status: Recruiting
• Phase: Phase 1
• Start date: July 1, 2021
• Est. completion date: July 31, 2025

Study information

• Verified date: June 2022
• Source: University of Kansas Medical Center
• Contact: Seth W Holwerda, Ph,D
• Phone: 9729223230
• Email: sholwerda[@]kumc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: July 31, 2025
• Est. primary completion date: July 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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.

Related Conditions & MeSH terms

• Blood Pressure
• Diabetes
• Diuretics Drug Reactions
• Drug-Related Side Effects and Adverse Reactions
• Insulin Resistance
• Obesity
• Sympathetic Nerve Activity

Intervention

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
• 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
• 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.

Locations

Country	Name	City	State
United States	University of Kansas Medical Center	Kansas City	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
University of Kansas Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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-a) and interlukin-6 (IL6) Blood Test: pg/mL normal values: IL-6 was 6-31 pg/mL and TNF-a 5 pg/mL,; Nitrotyrosine (Oxidative stress)	Baseline
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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-a) and interlukin-6 (IL6) Blood Test: pg/mL normal values: IL-6 was 6-31 pg/mL and TNF-a 5 pg/mL,; Nitrotyrosine (Oxidative stress)	4 Week
Primary	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
Primary	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