Nitric Oxide and the Autonomic Nervous System

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Italo Biaggioni, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00178919
First received: September 12, 2005
Last updated: May 24, 2013
Last verified: May 2013
  Purpose

The amount of blood flowing to the different parts of the body is regulated by the autonomic (automatic) nerves and by local factors produced by the blood vessels. Nitric oxide (NO) is one of the most important of these metabolic factors. If the production of NO is slowed or stopped the amount of blood to the different parts of the body is decreased. There is increasing knowledge that NO mechanisms are impaired in a number of medical conditions. NO function is reduced in patients with risk factors for atherosclerosis (hardening of the arteries) such as hypercholesterolemia (patients with high cholesterol), or diabetes mellitus, and is also impaired in smokers. This NO "deficiency" is believed to contribute to the greater cardiovascular risk that marks these patient populations. This study is designed to examine if endothelial nitric oxide is an important control mechanism of blood pressure under normal conditions, and if impairment of nitric oxide contributes to hypertension.


Condition Intervention
Hypertension
Pure Autonomic Failure
Drug: L-NMMA
Drug: Trimethaphan

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Official Title: Cardiovascular Regulation: Autonomic/Metabolic Mechanisms PO1 HL56693, Project 4: Cardiovascular Regulation: Autonomic/Metabolic Mechanisms

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Change in Systolic Blood Pressure [ Time Frame: At the end of the highest tolerated dose of IV infusion of L-NMMA ] [ Designated as safety issue: No ]
    L-NMMA (nitric oxide synthase inhibitor) was infused intravenously at different doses for 15 minutes each, after blocking the autonomic nervous system with trimethaphan. The change in systolic blood pressure at the end of the highest tolerated dose is the main outcome. Trimethaphan infused intravenously was used to produce transient blockade of the autonomic nervous system to allow for a full response to nitric oxide inhibition (in the absence of the baroreflex.

  • Systolic Blood Pressure in Response to Systemic Nitric Oxide Inhibition [ Time Frame: End of 15 minutes of infusion of L-NMMA at the highest tolerated dose ] [ Designated as safety issue: No ]
    Systolic blood pressure at the highest tolerated dose of IV infusion of L-NMMA during autonomic nervous system blockade with trimethaphan. Trimethaphan, infused intravenously was used to produce transient blockade of the autonomic nervous system to allow for a full response to nitric oxide inhibition (in the absence of the baroreflex.


Enrollment: 112
Study Start Date: August 2002
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Autonomic Failure Patients
To compare the effects of NO inhibition during intact and transient pharmacological blockade of the autonomic nervous system in Patients with Autonomic Failure.
Drug: L-NMMA
IV infusion of 125, 250 and 500 mcg/Kg/min for 15 minutes each dose. The main outcome is the maximal increase in blood pressure produced at the end of the infusions or a maximal systolic blood pressure of 160 mm Hg. It could be achieved after the first dose or the third.
Drug: Trimethaphan
IV infusion for the duration of the study at 4-6 mg/min depending on autonomic blockade. This is only to produce transient pharmacological blockade of the autonomic nervous system in order to allow the full expression of the inhibition of nitric oxide synthase. There is no direct outcome associated with this intervention.
Experimental: Controls and hypertensives
To compare the effects of NO inhibition during intact and transient pharmacological blockade of the autonomic nervous system in normal volunteers and hypertensive subjects.
Drug: L-NMMA
IV infusion of 125, 250 and 500 mcg/Kg/min for 15 minutes each dose. The main outcome is the maximal increase in blood pressure produced at the end of the infusions or a maximal systolic blood pressure of 160 mm Hg. It could be achieved after the first dose or the third.
Drug: Trimethaphan
IV infusion for the duration of the study at 4-6 mg/min depending on autonomic blockade. This is only to produce transient pharmacological blockade of the autonomic nervous system in order to allow the full expression of the inhibition of nitric oxide synthase. There is no direct outcome associated with this intervention.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Adult subjects.
  • 18 to 85 years.
  • Non-smokers or long term smokers for specific aim 6.
  • Drug-free.
  • Long term hypertension in specific substudy 3, patients with autonomic failure in specific aims 4 and 5, diabetes mellitus in specific aim 5.

Exclusion Criteria:

  • Being on any medication other than antihypertensives (for hypertensives), autonomic medications (for autonomic failure [AF] patients), insulin or other treatment for diabetes (for diabetic patients).
  • Having pulmonary, renal, hematopoietic, hepatic and/or cardiac disease.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00178919

Locations
United States, Tennessee
Autonomic Dysfunction Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Italo Biaggioni, M.D. Vanderbilt University
  More Information

No publications provided by Vanderbilt University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Italo Biaggioni, Professor of Medicine, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00178919     History of Changes
Other Study ID Numbers: 010876, NIH 1RO1HL71172
Study First Received: September 12, 2005
Results First Received: April 10, 2009
Last Updated: May 24, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt University:
Endothelial Nitric Oxide
L-NMMA
Trimethaphan
Autonomic Nervous System
Nitric Oxide Inhibition

Additional relevant MeSH terms:
Hypertension
Pure Autonomic Failure
Autonomic Nervous System Diseases
Cardiovascular Diseases
Nervous System Diseases
Primary Dysautonomias
Vascular Diseases
Nitric Oxide
Trimethaphan
Trimethaphan camsylate
Adjuvants, Anesthesia
Anti-Asthmatic Agents
Antihypertensive Agents
Antioxidants
Autonomic Agents
Bronchodilator Agents
Cardiovascular Agents
Central Nervous System Agents
Cholinergic Agents
Cholinergic Antagonists
Endothelium-Dependent Relaxing Factors
Free Radical Scavengers
Ganglionic Blockers
Gasotransmitters
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Nicotinic Antagonists
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014