Role of Sympathetic Activity and Splanchnic Capacitance in Hypertension

NCT02425566 | Active Not Recruiting Phase 1

• 1 other identifier: 141218
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to better understand the role of the abdominal veins (splanchnic capacitance) and the sympathetic nervous system in human hypertension. The investigators will test the hypothesis that constriction of abdominal veins due to sympathetic activation contributes to human hypertension. Splanchnic capacitance will be assessed in normotensive and hypertensive subjects at baseline and during acute blockade of the autonomic nervous system.

Conditions

Hypertension

Keywords

autonomic nervous system; hypertension; ganglionic blocker; trimethaphan; splanchnic circulation; capacitance

Outcome Measures

Primary Outcomes (1)

• Splanchnic venous capacitance

  The primary outcome will be the splanchnic capacitance, defined as the pressure-venous curve (P-V curve), during trimethaphan infusion adjusted for its baseline values. For analysis, the Y-intercept (volume) and the slope of the P-V relationship during autonomic blockade adjusted by their corresponding baseline values will be compared between groups.

  after 10 minutes of autonomic blockade

Secondary Outcomes (2)

• Systolic Blood Pressure

  after 10 minutes of autonomic blockade

• Stroke volume

  after 10 minutes of autonomic blockade

Study Arms (2)

Study day with trimethaphan

EXPERIMENTAL

After baseline measurements, autonomic blockade will be induced by continuous intravenous infusion of trimethaphan starting at 0.5-1.0 mg/min and increasing by 1.0 mg/min every 2 to 6 minutes up to an infusion rate of 5 mg/min.

Drug: Trimethaphan

Radionuclide Study day with nitroglycerin

EXPERIMENTAL

Sublingual nitroglycerin (0.3-0.6 mg) will be given after baseline measurements. Outcome measurements will be repeated within 10 min after the nitroglycerin has dissolved

Drug: Nitroglycerin

Interventions

Trimethaphan DRUG

Trimethaphan is a Nn-nicotinic receptor antagonist that blocks sympathetic and parasympathetic transmission at the level of the autonomic ganglia. It will be administered as an acute intravenous infusion with doses ranging from 0.5 to 5.0 mg/min.

Also known as: Trimethaphan Camsylate

Study day with trimethaphan

Nitroglycerin DRUG

Sublingual nitroglycerin (0.3-0.6 mg) will be given after baseline measurements.

Also known as: Nitroglycerin sublingual, nitrostat

Radionuclide Study day with nitroglycerin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Lean and obese, male and female subjects of all races between 18 and 65 years of age.
• Normotensive and hypertensive subjects will be enrolled. Hypertension will be defined as a systolic BP ≥140 mm Hg and/or a diastolic BP ≥ 90 mm Hg, taken in the seated position in at least 2 separate occasions. All subjects will be otherwise normal volunteers.
• Subjects able and willing to provide informed consent.

You may not qualify if:

• Pregnancy.
• Subjects with morbid obesity (BMI \> 40 kg/m2).
• Subjects with any chronic disease (other than hypertension) including diabetes, cardiovascular disease, history of smoking, or if they take any medication that have known effects autonomic functions, or other factors which in the investigator's opinion would prevent the subject from completing the protocol including clinically significant abnormalities in clinical, mental or laboratory testing.
• Current smokers or history of heavy smoking (\>2 packs/day)
• Lean normotensive subjects will be excluded if they have a strong family history of hypertension (both parents treated or diagnosed), diagnosis of sleep apnea or a high score in the Berlin questionnaire for sleep apnea, or if they are highly trained athletes.

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Autonomic Dysfunction Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• Okamoto LE, Dupont WD, Biaggioni I, Kronenberg MW. Effect of nitroglycerin on splanchnic and pulmonary blood volume. J Nucl Cardiol. 2022 Dec;29(6):2952-2963. doi: 10.1007/s12350-021-02811-7. Epub 2021 Nov 2.

  PMID: 34729682 DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

Trimethaphan; trimethaphan camsylate; Nitroglycerin

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitro Compounds; Organic Chemicals

Study Officials

• Italo Biaggioni, MD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: April 10, 2015
• First Posted: April 24, 2015
• Study Start: April 1, 2015
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: August 21, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)