MAPLE: Mitigating the Pro-inflammatory Phenotype of Obesity
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 |
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Phase 1 |
Detailed Description
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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.
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Determine the extent to which inflammation in the body is caused by elevated sympathetic nerve activity
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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.
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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:
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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:
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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
Inclusion Criteria:
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Male or Female, age 18-79
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Obese: BMI > 30 m/kg2
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Hypertensive: blood pressure >130/80
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Elevated insulin resistance (HOMA-IR > 2.5)
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Waist circ: >102 cm (men) and >88 cm (women)
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Fasting glucose < 126 mg/dL
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Fasting triglycerides < 250 mg/dL
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HbA1c < 6.5%
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Willing to visit research lab (Fairway CTSU)
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Willing to undergo a blood draw
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Able to provide written informed consent
Exclusion Criteria:
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Current use of clonidine or beta-blockers
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Current smoker or History of smoking in the past 3 months.
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Hyperlipidemia: Fasting triglycerides > 250 mg/dL
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Currently taking hypertension medication
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History of heart disease (e.g., myocardial infarction, stent, byass, heart attack, stroke, heart failure, valvular heart disease, cardiomyopathy)
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History of neurological disorders
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History of transplant
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Actively participating in other studies, except for a registry study.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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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.- 00147099