MAPLE: Mitigating the Pro-inflammatory Phenotype of Obesity

Sponsor

University of Kansas Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04934228

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Blood Pressure Diabetes Obesity Insulin Resistance Diuretics Drug Reactions Sympathetic Nerve Activity	Drug: Hydrochlorothiazide 12.5Mg Tab Drug: Clonidine Pill Drug: Placebo	Phase 1

Detailed Description

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.
Determine the extent to which inflammation in the body is caused by elevated sympathetic nerve activity

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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

Masking:

Double (Participant, Investigator)

Masking Description:

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.

Primary Purpose:

Other

Official Title:

Mitigating the Pro-inflammatory Phenotype of Obesity

Actual Study Start Date :

Jul 1, 2021

Anticipated Primary Completion Date :

Jul 31, 2025

Anticipated Study Completion Date :

Jul 31, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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 [Baseline]
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)
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 [Baseline]
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,
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 [Baseline]
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
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 [1 Week]
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.
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 [2 Week]
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.
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 [4 Week]
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)
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 [4 Week]
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,
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 [4 Week]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 79 Years

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Kansas Medical Center	Kansas City	Kansas	United States	66103

Sponsors and Collaborators

University of Kansas Medical Center

Investigators

Principal Investigator: Seth W. W Holwerda, PhD, University of Kansas Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Seth Holwerda PhD, Principal Investigator, University of Kansas Medical Center

ClinicalTrials.gov Identifier:

NCT04934228

Other Study ID Numbers:

00147099

First Posted:

Jun 22, 2021

Last Update Posted:

Jun 21, 2022

Last Verified:

Jun 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Study Results

No Results Posted as of Jun 21, 2022