Role of Sympathetic Vasoconstriction on Insulin-Mediated Microvascular Recruitment and Glucose Uptake in Obesity

NCT03318094 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 162097
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to better understand the contribution of sympathetic vasoconstriction to impaired insulin-mediated vasodilation and subsequently insulin-mediated glucose uptake. The investigators will test the hypothesis that removal of sympathetic vasoconstriction can result in improvement in insulin-mediated vasodilation and subsequently sensitivity to insulin-mediated glucose uptake.

Conditions

Healthy; Insulin Resistance; Obesity

Keywords

insulin resistance; phentolamine; microvascular recruitment; autonomic nervous system

Outcome Measures

Primary Outcomes (1)

• Contrast Enhanced-Ultrasonography (CEU)

  The Primary Outcome will be the change in CEU induced by insulin during hyperinsulinemic clamp compared to baseline. To test the null hypothesis that insulin will not produce any changes in microvascular blood volume using CEU in response to α-adrenergic blockade (phentolamine) in the isolated forearm model.

  Before clamp and 15 minutes after clamp

Study Arms (3)

Intact Day

PLACEBO COMPARATOR

Saline

Other: Saline

Blocked Day

EXPERIMENTAL

Phentolamine

Drug: Phentolamine

Vasodilator Comparison

ACTIVE COMPARATOR

Sodium Nitroprusside

Drug: Sodium Nitroprusside

Interventions

Phentolamine DRUG

Intrabrachial phentolamine will be given on the blocked day

Also known as: alpha-adrenergic blocker

Blocked Day

Saline OTHER

Intrabrachial saline will be given this day

Intact Day

Sodium Nitroprusside DRUG

Intrabrachial sodium nitroprusside will be given this day to compare with phentolamine

Also known as: Active comparison

Vasodilator Comparison

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males and females of all races between 18 and 60 years of age.
• Obesity defined as body mass index between 30-40 kg/m2
• Insulin resistance defined as homeostasis model assessment 2 insulin resistance (HOMA2-IR) score \>1.6 (never diagnosed or treated type 2 diabetic), or being a well-controlled type 2 diabetic on metformin only.
• Able and willing to provide informed consent

You may not qualify if:

• Pregnancy or breastfeeding
• Current smokers or history of heavy smoking (\>2 packs/day)
• History of alcohol or drug abuse
• Morbid obesity (BMI \> 40 kg/m2)
• Previous allergic reaction to study medications
• Evidence of type I diabetes.
• Cardiovascular disease other than hypertension such as myocardial infarction within 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third-degree heart block, mitral valve stenosis, aortic stenosis, or hypertrophic cardiomyopathy
• History of serious cerebrovascular disease such as cerebral hemorrhage, stroke, or transient ischemic attack
• History or presence of immunological or hematological disorders
• Impaired hepatic function \[aspartate amino transaminase (AST) and/or alanine amino transaminase (ALT) \> 2.0 x upper limit of normal range\]
• Impaired renal function (serum creatinine \>1.5 mg/dl)
• Moderate to severe anemia (hemoglobin \<11 g/dl)
• Treatment with serotonin-norepinephrine reuptake inhibitors (SNRIs) or norepinephrine transporter (NET) inhibitors
• Treatment with phosphodiesterase 5 inhibitors
• Treatment with anticoagulants

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Autonomic Dysfunction Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Insulin Resistance; Obesity

Interventions

Phentolamine; Adrenergic alpha-Antagonists; Sodium Chloride; Nitroprusside

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Ferricyanides; Cyanides; Anions; Ions; Electrolytes; Ferric Compounds; Iron Compounds; Hydrogen Cyanide; Nitrogen Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Medicine and Pharmacology

Study Record Dates

• First Submitted: October 17, 2017
• First Posted: October 23, 2017
• Study Start: October 24, 2017
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2027
• Last Updated: March 2, 2026

Record last verified: 2026-02

Locations

US (1)