- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04329806
Sympathetic Mechanisms in the Cardiovascular and Metabolic Alterations of Obesity
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Continuing Review (CR, 2021/08/04) Update: Removal of the angiotensin receptor blockade arm of the study
The presence of obesity increases the risk for hypertension and diabetes, in part due to the development of insulin resistance. Obesity is also associated with sympathetic activation and the overarching hypothesis is that sympathetic activation contributes to insulin resistance with impairment of its vascular and metabolic actions. Preliminary studies suggest that 1) Blood pressure can be normalized by autonomic blockade in obese hypertensives, 2) Sympathetic activation provides no metabolic benefit because the increase in resting energy expenditure associated with obesity is due to an increase in fat free mass rather than sympathetic activation. On the contrary, autonomic blockade: 3) Improves insulin sensitivity in obese hypertensives, 4) Reverses their impaired NO-mediated dilation, and 5) Reduces plasma isoprostanes, a measure of oxidative stress. Furthermore, these abnormalities are interrelated in negative feedback loops, whereby inflammation/oxidative stress impairs nitric oxide mechanisms, which in turn reduces insulin-mediated vasodilation important for substrate delivery, thus contributing to insulin resistance; insulin resistance leads to compensatory increases in insulin levels, which contributes to further sympathetic activation. Current treatment guidelines do not specifically address the treatment of obesity hypertension, and do not target sympathetic activation as a first line approach. It is important, therefore, to determine whether or not targeting sympathetic activation offers unique advantages in the treatment of obesity hypertension over current approaches. The investigators propose a proof-of-concept mechanistic study comparing the metabolic, vascular, and anti-inflammatory effects of sympathetic inhibition, calcium channel blockade and angiotensin receptor blockade in obesity hypertension. The investigators will test the hypotheses that sympathetic activation contributes to 1) metabolic insulin resistance, which impairs the suppression of endogenous glucose production and the stimulation of glucose uptake normally provided by insulin, 2) vascular insulin resistance, which impairs insulin-mediated vasodilation and microvascular recruitment that normally promote glucose uptake, and 3) inflammation and oxidative stress, which contribute to insulin resistance and hypertension. The proposed studies will gauge the contribution of sympathetic activation to the cardiovascular and metabolic complications of obesity and provide the mechanistic insight to determine whether or not it should foster the efforts currently under way to develop novel therapies targeting sympathetic activation for hypertension.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Cynthia D Laws, MS,RHIA,CCRP
- Phone Number: 615-421-1994
- Email: autonomicgroup@vumc.org
Study Contact Backup
- Name: Alfredo Gamboa
- Phone Number: 615-875-1003
- Email: alfredo.gamboa@vumc.org
Study Locations
-
-
Tennessee
-
Nashville, Tennessee, United States, 37232
- Recruiting
- Vanderbilt University
-
Contact:
- Cynthia D Laws, MS, RHIA,ASQ-CQIA, CCRP
- Phone Number: 615-421-1994
- Email: autonomicgroup@vumc.org
-
Sub-Investigator:
- Andre Diedrich, MD/PhD
-
Sub-Investigator:
- Emily C Smith
-
Sub-Investigator:
- Luis E Okamoto, MD
-
Principal Investigator:
- Italo Biaggioni, MD
-
Sub-Investigator:
- Alfredo Gamboa, MD
-
Sub-Investigator:
- Cyndya A Shibao, MD
-
Contact:
- Emily C Smith, RN
- Phone Number: 615.875.1516
- Email: autonomics@vumc.org
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Males and females of all races between 18 and 60 years of age
- Hypertension defined by two or more properly measured seated blood pressure readings >130/85 mmHg or currently on antihypertensive medication.
- Obesity will be defined as having a body mass index (BMI) ≥ 30 kg/m2.
- Able and willing to provide informed consent.
Exclusion Criteria:
- Pregnancy or breast feeding
- Current smokers or history of heavy smoking (>2 packs/day)
- History of alcohol or drug abuse
- Previous allergic reaction to study medications
- Evidence of type I diabetes
- Cardiovascular disease other than hypertension
- History of serious cerebrovascular disease
- History or presence of immunological or hematological disorders
- Impaired renal function
- Treatment with any investigational drug in the 1 month preceding the study
- Inability to give, or withdraw, informed consent
- Other factors which in the investigator's opinion would prevent the subject from completing the protocol
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Moxonidine
Moxonidine to be administered at a dose to produce a decrease in BP of at least 20% of baseline for 9 weeks
|
Moxonidine 0.2 MG twice daily
|
Active Comparator: Amlodipine
Amlodipine to be administered at a dose to produce a decrease in BP of at least 20% of baseline for 9 weeks
|
Amlodipine 5 MG twice daily
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Insulin Sensitivity
Time Frame: 6 hours
|
Dose response curve to insulin ( measure as glucose infusion rate In mg/kg/min)
|
6 hours
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Italo Biaggioni, MD, Vanderbilt University Medical Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Overnutrition
- Nutrition Disorders
- Overweight
- Body Weight
- Hyperinsulinism
- Obesity
- Insulin Resistance
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Vasodilator Agents
- Membrane Transport Modulators
- Calcium-Regulating Hormones and Agents
- Calcium Channel Blockers
- Amlodipine
- Moxonidine
Other Study ID Numbers
- 190479
- R01HL149386 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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