Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Exhaled Levels of Nitric Oxide

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. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00753948
Recruitment Status : Completed
First Posted : September 17, 2008
Results First Posted : July 4, 2014
Last Update Posted : July 4, 2014
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development ( US Department of Veterans Affairs )

Brief Summary:

Previously it was observed that individuals with tetraplegia have reduced baseline airway caliber and exhibit non-specific airway hyperresponsiveness (AHR). In persons with tetraplegia we have suggested that this is due to overriding cholinergic airway tone. In asthma, the mechanisms underlying bronchoconstriction and AHR are more closely tied to airway inflammation. Whether AHR in tetraplegia is also related to chronic airway inflammation is unknown.

Recently, a non-invasive technique for assessing airway inflammation has been established in asthma that involves measurement of nitric oxide (NO) concentrations (FeNO) in expired air. FeNO is elevated in asthma likely due to excess NO production by inflammatory cells within the airway Measurement of FeNO in persons with tetraplegia would help in assessing the role of airway inflammation in this population. This may have therapeutic significance in such individuals. NO in the lung is felt to be the principal inhibitory neurotransmitter of the non-adrenergic, non-cholinergic (NANC) system. It is thought that inhalation of NO has no effect on airway tone in healthy individuals but reduces methacholine responsiveness while having weak direct bronchodilatory effect in asthmatics.

The primary purpose of this study is to determine the levels of exhaled NO (FeNO) in individuals with chronic cervical spinal cord injury (SCI), and to compare them with those obtained in age and sex matched able-bodied individuals and subjects with stable mild to moderate asthma. If the FeNO levels are high and comparable to those found in asthmatic subjects, this will imply the role of chronic inflammation in reduced baseline airway caliber and non-specific airway hyper-responsiveness (AHR) exhibited by individuals with chronic cervical SCI. If the FeNO levels are comparable with those found in able-bodied controls, this will support our previous statement that unopposed cholinergic innervation is responsible for low baseline airway caliber and AHR in individuals with chronic tetraplegia. Further scientific conclusions about NO and its role in control of airway tone, pulmonary resistances and blood pressure will be drawn upon intravenous and inhaled administration of L-NAME. This compound has been shown promising results for the treatment and prevention of orthostatic hypotension in individuals with tetraplegia. Knowing its effects on airways and potential of easier mode of delivery (inhalation vs. intravenous) is of utmost importance.


Condition or disease Intervention/treatment Phase
Tetraplegia Asthma Drug: N-Nitro L-arginine-methylester (L-NAME) Phase 2 Phase 3

Detailed Description:
The study requires a maximum of five study visits in the following order: 1. nebulized normal saline, 2. nebulized 1mg/kg of L-NAME (see below), 3. intravenous normal saline, 4. intravenous 1 mg/kg L-NAME, 5. intravenous 2 mg/kg L-Name.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Official Title: The Effect of Nitric Oxide on Pulmonary Resistances and Blood Pressure in Persons With Tetraplegia
Study Start Date : December 2006
Actual Primary Completion Date : August 2010
Actual Study Completion Date : August 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Experimental: Arm 1
Individuals with chronic tetraplegia
Drug: N-Nitro L-arginine-methylester (L-NAME)
A non-specific inhibitor of the nitric oxide synthase enzyme.

Active Comparator: Arm 2
Individuals with diagnosed mild asthma
Drug: N-Nitro L-arginine-methylester (L-NAME)
A non-specific inhibitor of the nitric oxide synthase enzyme.

Placebo Comparator: Arm 3
Neurologically intact, otherwise healthy, age-matched control
Drug: N-Nitro L-arginine-methylester (L-NAME)
A non-specific inhibitor of the nitric oxide synthase enzyme.




Primary Outcome Measures :
  1. Exhaled Levels of Nitric Oxide [ Time Frame: Exhaled NO was reported as the mean of three values within 10% of each other. ]
    Nitric Oxide was measured applying a real time technique for measurement of Nitric Oxide in Exhaled Breath Condensate. Elevated Nitric Oxide in exhalate is a measure of elevated production of NO in conditions such as underlying inflammation and/or oxidative stress


Secondary Outcome Measures :
  1. Lung Function as Measured by Plethysmography [ Time Frame: During study visits, measures are obtained prior to intervention (intravenous or nebulized) and 60, 120 minutes post intervention. ]
  2. Methacholine Challenge [ Time Frame: During study visits, methacholine challenge will be performed 120 minutes post intervention. ]


Information from the National Library of Medicine

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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Written informed consent.
  2. Age between 18 and 65 years.
  3. Able-bodied individuals, persons with mild asthma or individuals with tetraplegia for at least one year of duration.
  4. Able to perform acceptable pulmonary function tests and follow procedures.

Exclusion Criteria:

  1. coronary artery disease;
  2. active cigarette smokers or previous smokers who stopped <5 years ago;
  3. MI or stroke within 3 months;
  4. moderate to severe reduction in lung function defined as FEV1 < 70 % predicted (except in individuals with tetraplegia);
  5. hypertension;
  6. medications known to affect the cardiovascular system;
  7. pregnancy
  8. current use of cholinesterase medication; and
  9. lack of mental capacity to give informed consent Group specific exclusion criteria for

Asthmatic subjects:

  1. Moderate to severe disease as per spirometric indices;
  2. testing within 48 hours of last administration of long acting inhaled bronchodilator;
  3. testing within 7 days of last administration of glucocorticoids;
  4. testing within > 24 hours since last administration of leukotriene modifiers; and
  5. testing within 8 hours of last administration of a short acting bronchodilator medication

Information from the National Library of Medicine

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): NCT00753948


Locations
Layout table for location information
United States, New York
VA Medical Center, Bronx
Bronx, New York, United States, 10468
Sponsors and Collaborators
US Department of Veterans Affairs
Investigators
Layout table for investigator information
Principal Investigator: Miroslav Radulovic, MD VA Medical Center, Bronx

Publications of Results:
Layout table for additonal information
Responsible Party: US Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00753948     History of Changes
Other Study ID Numbers: B4335-V
First Posted: September 17, 2008    Key Record Dates
Results First Posted: July 4, 2014
Last Update Posted: July 4, 2014
Last Verified: May 2014

Keywords provided by VA Office of Research and Development ( US Department of Veterans Affairs ):
Tetraplegia
Mild asthma
Exhaled Nitric Oxide
NOS inhibitor
Spinal cord injury
Pulmonary Function

Additional relevant MeSH terms:
Layout table for MeSH terms
Quadriplegia
Paralysis
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Nitric Oxide
Nitroarginine
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Gasotransmitters
Protective Agents
Enzyme Inhibitors