|
|
Home
Search
Study Topics
Glossary
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||
| Sponsored by: |
Department of Veterans Affairs |
|---|---|
| Information provided by: | Department of Veterans Affairs |
| ClinicalTrials.gov Identifier: | NCT00753948 |
Purpose
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 | Intervention | Phase |
|---|---|---|
|
Tetraplegia Asthma |
Drug: N-Nitro L-arginine-methylester (L-NAME) |
Phase II Phase III |
| Study Type: | Interventional |
| Study Design: | Non-Randomized, Open Label, Crossover Assignment |
| Official Title: | The Effect of Nitric Oxide on Pulmonary Resistances and Blood Pressure in Persons With Tetraplegia |
| Estimated Enrollment: | 36 |
| Study Start Date: | December 2006 |
| Estimated Study Completion Date: | December 2009 |
| Estimated Primary Completion Date: | December 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
1: Experimental
Individuals with chronic tetraplegia
|
Drug: N-Nitro L-arginine-methylester (L-NAME)
A non-specific inhibitor of the nitric oxide synthase enzyme.
|
|
2: Active Comparator
Individuals with diagnosed mild asthma
|
Drug: N-Nitro L-arginine-methylester (L-NAME)
A non-specific inhibitor of the nitric oxide synthase enzyme.
|
|
3: Placebo Comparator
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.
|
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.
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion Criteria:
Asthmatic subjects:
Contacts and Locations| Contact: Michael F LaFountaine, EdD | (718) 584-9000 ext 3121 | Michael.lafountaine@va.gov |
| United States, New York | |
| VA Medical Center, Bronx | Recruiting |
| Bronx, New York, United States, 10468 | |
| Contact: Miroslav Radulovic, MD 718-584-9000 ext 5472 miroslav.radulovic@va.gov | |
| Principal Investigator: Miroslav Radulovic, MD | |
| Principal Investigator: | Miroslav Radulovic, MD | VA Medical Center, Bronx |
More Information
| Responsible Party: | Department of Veterans Affairs ( Radulovic, Miroslav - Principal Investigator ) |
| Study ID Numbers: | B4335V |
| Study First Received: | September 15, 2008 |
| Last Updated: | September 15, 2008 |
| ClinicalTrials.gov Identifier: | NCT00753948 |
| Health Authority: | United States: Federal Government; United States: Food and Drug Administration |
|
Tetraplegia Mild asthma Exhaled Nitric Oxide |
NOS inhibitor Spinal cord injury Pulmonary Function |
|
Asthma Quadriplegia Paralysis Nitric Oxide Spinal Cord Injuries Signs and Symptoms NG-Nitroarginine Methyl Ester |
Lung Diseases, Obstructive Hypersensitivity Respiratory Tract Diseases Lung Diseases Hypersensitivity, Immediate Neurologic Manifestations Respiratory Hypersensitivity |
|
Respiratory System Agents Vasodilator Agents Neurotransmitter Agents Antioxidants Bronchial Diseases Immune System Diseases Molecular Mechanisms of Pharmacological Action Nervous System Diseases Physiological Effects of Drugs Anti-Asthmatic Agents |
Cardiovascular Agents Protective Agents Pharmacologic Actions Autonomic Agents Therapeutic Uses Free Radical Scavengers Endothelium-Dependent Relaxing Factors Peripheral Nervous System Agents Bronchodilator Agents |
