Neural Mechanism of Aldosterone-induced Insulin Resistance
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT02102243 |
Recruitment Status :
Recruiting
First Posted : April 2, 2014
Last Update Posted : March 23, 2022
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Hypertension | Drug: DEFINITY® infusion Drug: Human Recombinant Regular Insulin infusion Drug: Dextrose infusion Procedure: Flow mediated vasodilation Procedure: Endothelial cell collection Procedure: Microvascular perfusion assessment using Definity Procedure: Microneurography | Phase 4 |
Patients with primary aldosteronism are known to have impaired insulin sensitivity, which is improved after removal of aldosterone-producing adenoma. In patients with essential hypertension, plasma aldosterone levels have been also shown to positively correlate with indices of insulin resistance.
Mechanism underlying aldosterone-induced insulin resistance is unknown. Aldosterone has been shown to interfere with insulin signaling the vascular cells by increasing production of reactive oxygen species via activation of NADPH oxidase, resulting in decreased availability of nitric oxide (NO), the key mediator for insulin-mediated vasodilation. Treatment with mineralocorticoid receptor antagonists has been shown to improve insulin sensitivity in mice with obesity and metabolic syndrome. Aldosterone has also been shown to increase resting sympathetic vasoconstrictor activity to the peripheral circulation. However, effects of aldosterone and mineralocorticoid receptor antagonists on insulin-mediated skeletal muscle vasodilation, sympathetic activation, and vascular oxidative stress have not been assessed in humans.
The investigators will collect venous endothelial cells, and measure skeletal muscle microvascular perfusion using Octafluoropropane microbubble contrast agents, and measure sympathetic nerve activity in normotensive controls (NT), stage 1 essential hypertensive subjects (ET), and patients with primary aldosteronism (PA) during hyperinsulinemic euglycemic clamp.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 2 participants |
Allocation: | Randomized |
Intervention Model: | Crossover Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Diagnostic |
Official Title: | The Role of Aldosterone on Sympathetic Nerve Activity and Insulin Sensitivity |
Study Start Date : | November 2010 |
Estimated Primary Completion Date : | December 2025 |
Estimated Study Completion Date : | December 2025 |

Arm | Intervention/treatment |
---|---|
Experimental: Hyperinsulinemic euglycemic clamp
We will perform following procedures: DEFINITY® infusion Flow mediated vasodilation Endothelial cell collection Microvascular perfusion assessment using Definity Microneurography |
Drug: DEFINITY® infusion
The DEFINITY® vial contains components that upon activation yield perflutren lipid microspheres, a diagnostic drug that is intended to be used for contrast enhancement during echocardiographic procedures. The vial contains a clear, colorless, sterile, non-pyrogenic, hypertonic liquid, which upon activation with agitation, provides a homogeneous, opaque, milky white injectable suspension of perflutren lipid microspheres. The suspension of activated DEFINITY® will be infused intravenously at a rate of 0.20 to 0.27 ml/min, not to exceed a maximum dose of 2 vials per study subject per day or visit.
Other Name: (IND# 104397) Drug: Human Recombinant Regular Insulin infusion The plasma insulin concentration will be acutely raised and maintained at at a steady state by a prime-continuous insulin infusion.
Other Names:
Drug: Dextrose infusion The plasma glucose concentration will be held constant at 90 mg/dl by a variable glucose infusion during euglycemic hyperinsulinemic clamp
Other Name: Dextrose 20% Procedure: Flow mediated vasodilation Flow mediated vasodilation (FMD), which is a non-invasive assessment of endothelial function, will be performed on the brachial artery using ultrasound. After a clear picture of the artery has been obtained, the cuff on the same arm will be inflated until it is tight for five minutes. During and following this, the subject's arm will continue to be imaged to monitor maximal increase in the brachial artery diameter.
Other Names:
Procedure: Endothelial cell collection We will collect endothelial cells from a superficial vein, usually in the arm. Following insertion of a peripheral intravenous (IV) catheter, we will collect cells from the inner lining of the vein using a thin, flexible J-tipped wire. The wire will be inserted through the IV into the vein and then removed, along with a sampling of endothelial cells. The cells collected will be processed and stained for several proteins involved in endothelial cell function, using immunofluorescent technique. Procedure: Microvascular perfusion assessment using Definity Using high-resolution ultrasound, we will measure skeletal muscle blood flow during infusion of a solution containing the octafluoropropane microbubble contrast agent, Definity. The solution will be a dilution of 1 vial of Definity to 30 cc of normal saline. The ultrasound probe will be placed over the forearm to obtain images while octafluoropropane microbubbles (Definity) are infused intravenously at the rate of 0.20 to 0.27 ml/min, not to exceed a maximum dose of 2 vials per study subject per day or visit. The microvascular perfusion assessment using Definity be performed at rest as well as during slow and fast handgrip exercises. Procedure: Microneurography Sympathetic nerve activity from the peroneal nerve measured by inserting a tiny needle directly into the nerve in the leg. Investigators will localize the nerve by electrical stimulation over the skin using a blunt probe. .The recording needle will remain in position throughout the study.
Other Name: Assessment of sympathetic nerve activity (SNA) |
Experimental: Initial Saline Infusion
We will perform the following procedures: DEFINITY® infusion Human Recombinant Regular Insulin infusion Dextrose infusion Flow mediated vasodilation Endothelial cell collection Microvascular perfusion assessment using Definity Microneurography |
Drug: DEFINITY® infusion
The DEFINITY® vial contains components that upon activation yield perflutren lipid microspheres, a diagnostic drug that is intended to be used for contrast enhancement during echocardiographic procedures. The vial contains a clear, colorless, sterile, non-pyrogenic, hypertonic liquid, which upon activation with agitation, provides a homogeneous, opaque, milky white injectable suspension of perflutren lipid microspheres. The suspension of activated DEFINITY® will be infused intravenously at a rate of 0.20 to 0.27 ml/min, not to exceed a maximum dose of 2 vials per study subject per day or visit.
Other Name: (IND# 104397) Procedure: Flow mediated vasodilation Flow mediated vasodilation (FMD), which is a non-invasive assessment of endothelial function, will be performed on the brachial artery using ultrasound. After a clear picture of the artery has been obtained, the cuff on the same arm will be inflated until it is tight for five minutes. During and following this, the subject's arm will continue to be imaged to monitor maximal increase in the brachial artery diameter.
Other Names:
Procedure: Endothelial cell collection We will collect endothelial cells from a superficial vein, usually in the arm. Following insertion of a peripheral intravenous (IV) catheter, we will collect cells from the inner lining of the vein using a thin, flexible J-tipped wire. The wire will be inserted through the IV into the vein and then removed, along with a sampling of endothelial cells. The cells collected will be processed and stained for several proteins involved in endothelial cell function, using immunofluorescent technique. Procedure: Microvascular perfusion assessment using Definity Using high-resolution ultrasound, we will measure skeletal muscle blood flow during infusion of a solution containing the octafluoropropane microbubble contrast agent, Definity. The solution will be a dilution of 1 vial of Definity to 30 cc of normal saline. The ultrasound probe will be placed over the forearm to obtain images while octafluoropropane microbubbles (Definity) are infused intravenously at the rate of 0.20 to 0.27 ml/min, not to exceed a maximum dose of 2 vials per study subject per day or visit. The microvascular perfusion assessment using Definity be performed at rest as well as during slow and fast handgrip exercises. Procedure: Microneurography Sympathetic nerve activity from the peroneal nerve measured by inserting a tiny needle directly into the nerve in the leg. Investigators will localize the nerve by electrical stimulation over the skin using a blunt probe. .The recording needle will remain in position throughout the study.
Other Name: Assessment of sympathetic nerve activity (SNA) |
- Increase in muscle sympathetic nerve activity during hyperinsulinemic euglycemic clamp [ Time Frame: 1 day ]
- Change in microvascular blood flow during hyperinsulinemic euglycemic clamp. [ Time Frame: 1 day ]
- Change in microvascular blood flow during saline infusion. [ Time Frame: 1 day ]
- Change in endothelial cell protein expression after hyperinsulinemic euglycemic clamp [ Time Frame: 1 day ]
- Change in endothelial cell protein expression after saline infusion [ Time Frame: 1 day ]
- Increase in muscle sympathetic nerve activity during saline infusion [ Time Frame: 1 day ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- Normotensive controls
- Stage I (140-159/90-99 mmHg) untreated subjects with essential hypertension
- Patients with PA and stage I (140-159/90-99 mmHg) hypertension
Exclusion Criteria:
- Congestive heart failure or coronary artery disease
- Blood pressure averaging > 159/99 mmHg
- Serum creatinine > 1.5 mg/dL
- Diabetes mellitus or other systemic illness
- Left ventricular hypertrophy by echocardiography or ECG
- Pregnancy
- Hypersensitivity to spironolactone, chlorthalidone, amlodipine, human recombinant insulin or Definity
- Any history of substance abuse (other than tobacco)
- History of gouty arthritis
- Patients with right-to-left, bi-directional, or transient right-to-left cardiac shunts
- Hypersensitivity to perflutren, blood, blood products or albumin

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02102243
Contact: Debbie Arbique, DNP | (214)648-3188 | debbie.arbique@utsouthwestern.edu | |
Contact: Alejandro Velasco, MD | 2146483180 | alejandro.velasco@utsouthwestern.edu |
United States, Texas | |
UT Southwestern Medical Center | Recruiting |
Dallas, Texas, United States, 75390 | |
Contact: Debbie Arbique, DNP 214-648-3188 debbie.arbique@utsouthwestern.edu |
Principal Investigator: | Wanpen Vongpatanasin, MD | UT Southwestern Medical Center |
Responsible Party: | Wanpen Vongpatanasin, PROFESSOR, University of Texas Southwestern Medical Center |
ClinicalTrials.gov Identifier: | NCT02102243 |
Other Study ID Numbers: |
STU 102010-063 |
First Posted: | April 2, 2014 Key Record Dates |
Last Update Posted: | March 23, 2022 |
Last Verified: | March 2022 |
hypertension blood pressure sympathetic nerve activity vascular oxidative stress nitric oxide nitric oxide synthase (eNOS) endothelium |
endothelial dysfunction endothelial cell protein expression microvascular blood flow flow mediated dilation endothelial cell collection microbubbles Definity |
Hypertension Vascular Diseases Cardiovascular Diseases Insulin |
Insulin, Globin Zinc Hypoglycemic Agents Physiological Effects of Drugs |