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Mitigating the Pro-inflammatory Phenotype of Obesity (MAPLE)

Primary Purpose

Blood Pressure, Diabetes, Obesity

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Hydrochlorothiazide 12.5Mg Tab
Clonidine Pill
Placebo
Sponsored by
University of Kansas Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Blood Pressure

Eligibility Criteria

18 Years - 79 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • University of Kansas Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

Placebo

Clonidine

Hydrochlorothiazide (HCTZ)

Arm Description

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.

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

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

Outcomes

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
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
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
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
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
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
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
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
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

Secondary Outcome Measures

Full Information

First Posted
March 31, 2021
Last Updated
June 15, 2022
Sponsor
University of Kansas Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT04934228
Brief Title
Mitigating the Pro-inflammatory Phenotype of Obesity
Acronym
MAPLE
Official Title
Mitigating the Pro-inflammatory Phenotype of Obesity
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2021 (Actual)
Primary Completion Date
July 31, 2025 (Anticipated)
Study Completion Date
July 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Kansas Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. 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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Blood Pressure, Diabetes, Obesity, Insulin Resistance, Diuretics Drug Reactions, Sympathetic Nerve Activity

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Mixed Model ANOVA 3-way analysis of variance to assess pain and BP responses to the clonidine, diuretic vs. placebo.
Masking
ParticipantInvestigator
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.
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Clonidine
Arm Type
Experimental
Arm Description
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
Arm Title
Hydrochlorothiazide (HCTZ)
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Hydrochlorothiazide 12.5Mg Tab
Other Intervention Name(s)
Hydrochlorothiazide
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Clonidine Pill
Other Intervention Name(s)
Clonidine
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Will receive a 4 week supply (35 days) of Placebo Pills; has no active ingredients but is made to look like the study drug.
Primary Outcome Measure Information:
Title
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
Description
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)
Time Frame
Baseline
Title
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
Description
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,
Time Frame
Baseline
Title
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
Description
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
Time Frame
Baseline
Title
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
Description
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.
Time Frame
1 Week
Title
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
Description
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.
Time Frame
2 Week
Title
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
Description
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)
Time Frame
4 Week
Title
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
Description
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,
Time Frame
4 Week
Title
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
Description
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
Time Frame
4 Week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Seth W Holwerda, Ph,D
Phone
9729223230
Email
sholwerda@kumc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Davina A Clonch
Phone
9132266009
Email
dclonch@kumc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Seth W. W Holwerda, PhD
Organizational Affiliation
University of Kansas Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66103
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Seth W. W Holwerda
Phone
972-922-3230
Email
sholwerda@kumc.edu

12. IPD Sharing Statement

Plan to Share IPD
No

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Mitigating the Pro-inflammatory Phenotype of Obesity

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