TetraplegiaPhase 2/3NCT00753948
Exhaled Levels of Nitric Oxide
A Phase 2/3 study testing N-Nitro L-arginine-methylester (L-NAME) in people with Tetraplegia and Asthma, run by VA Office of Research and Development at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Tetraplegia, Asthma
- What is being tested?
- N-Nitro L-arginine-methylester (L-NAME)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2006to Aug 2010
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Written informed consent.
- Age between 18 and 65 years.
- Able-bodied individuals, persons with mild asthma or individuals with tetraplegia for at least one year of duration.
- Able to perform acceptable pulmonary function tests and follow procedures.
Who cannot join
- coronary artery disease;
- active cigarette smokers or previous smokers who stopped <5 years ago;
- MI or stroke within 3 months;
- moderate to severe reduction in lung function defined as FEV1 < 70 % predicted (except in individuals with tetraplegia);
- hypertension;
- medications known to affect the cardiovascular system;
Show all 15Show fewer
- pregnancy
- current use of cholinesterase medication; and
- lack of mental capacity to give informed consent Group specific exclusion criteria for
- Asthmatic subjects:
- Moderate to severe disease as per spirometric indices;
- testing within 48 hours of last administration of long acting inhaled bronchodilator;
- testing within 7 days of last administration of glucocorticoids;
- testing within > 24 hours since last administration of leukotriene modifiers; and
- testing within 8 hours of last administration of a short acting bronchodilator medication
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Nitric Oxide on Pulmonary Resistances and Blood Pressure in Persons With Tetraplegia
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.
Read the 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.
- Conditions
- Tetraplegia, Asthma
- Being tested
- N-Nitro L-arginine-methylester (L-NAME)
- Keywords
- Tetraplegia, Mild asthma, Exhaled Nitric Oxide, NOS inhibitor, Spinal cord injury, Pulmonary Function
- Medical subject headings
- Quadriplegia, Asthma, Spinal Cord Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-Nitro L-arginine-methylester (L-NAME)Drug
A non-specific inhibitor of the nitric oxide synthase enzyme.
| Study group | Role | What they receive |
|---|---|---|
| Chronic Tetraplegia | Experimental | Individuals with chronic tetraplegia Receives: Drug: N-Nitro L-arginine-methylester (L-NAME) |
| Mild Asthma | Active comparator | Individuals with diagnosed mild asthma Receives: Drug: N-Nitro L-arginine-methylester (L-NAME) |
| Healthy Control | Placebo comparator | Neurologically intact, otherwise healthy, age-matched control Receives: Drug: N-Nitro L-arginine-methylester (L-NAME) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Exhaled Levels of Nitric Oxide
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. Exhaled NO was reported as the mean of three values within 10% of each other.
Measured: Exhaled NO reported during visit, before intervention at baseline, post intervention at 60 minutes and 120 minutes
Secondary outcomes (1)
Specific Airway Conductance (sGaw) as Measured by Plethysmography
Specific airway conductance (sGaw) is the airway conductance relative to lung volume because it takes into account the important effect of lung volume on airway resistance, it is a useful index of bronchomotor tone.
Measured: Specific airway conductance reported during visit, before intervention at baseline, post intervention at 60 minutes and 120 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2008 (estimated)
- Study startDec 2006
- Primary completionAug 2010
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TetraplegiaStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Miroslav Radulovic, MD, Principal investigator, VA Medical Center, Bronx
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00753948
- Sponsor's protocol ID
- B4335-V
- Status last verified
- Feb 2020
- First submitted
- 15 Sep 2008
- Last updated
- 28 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Radulovic M, Schilero GJ, Wecht JM, La Fountaine M, Rosado-Rivera D, Bauman WA. Exhaled nitric oxide levels are elevated in persons with tetraplegia and comparable to that in mild asthmatics. Lung. 2010 Jun;188(3):259-62. doi: 10.1007/s00408-009-9207-x. Epub 2009 Dec 15.
PubMed 20012982
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Nitric Oxide on Pulmonary Resistances and Blood Pressure in Persons With Tetraplegia
- ClinicalTrials.gov ID
- NCT00753948
- Acronym / sponsor ID
- B4335-V
- Conditions
- Tetraplegia, Asthma
- Keywords
- Tetraplegia, Mild asthma, Exhaled Nitric Oxide, NOS inhibitor, Spinal cord injury, Pulmonary Function
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- Dec 2006
- Primary completion
- Aug 2010 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 17 Sep 2008 (estimated)
- Results
- Posted 4 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Chronic Tetraplegia | Experimental | Drug: N-Nitro L-arginine-methylester (L-NAME)Individuals with chronic tetraplegia |
| Mild Asthma | Active comparator | Drug: N-Nitro L-arginine-methylester (L-NAME)Individuals with diagnosed mild asthma |
| Healthy Control | Placebo comparator | Drug: N-Nitro L-arginine-methylester (L-NAME)Neurologically intact, otherwise healthy, age-matched control |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Written informed consent.
- Age between 18 and 65 years.
- Able-bodied individuals, persons with mild asthma or individuals with tetraplegia for at least one year of duration.
- Able to perform acceptable pulmonary function tests and follow procedures.
Key exclusion criteria (15 listed)
- coronary artery disease;
- active cigarette smokers or previous smokers who stopped <5 years ago;
- MI or stroke within 3 months;
- moderate to severe reduction in lung function defined as FEV1 < 70 % predicted (except in individuals with tetraplegia);
- hypertension;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-Nitro L-arginine-methylester (L-NAME)A non-specific inhibitor of the nitric oxide synthase enzyme. | Drug | Chronic Tetraplegia, Healthy Control, Mild Asthma |
Primary outcome
Exhaled Levels of Nitric Oxide
Time frame: Exhaled NO reported during visit, before intervention at baseline, post intervention at 60 minutes and 120 minutes
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. Exhaled NO was reported as the mean of three values within 10% of each other.
1 secondary outcome
Specific Airway Conductance (sGaw) as Measured by Plethysmography
Time frame: Specific airway conductance reported during visit, before intervention at baseline, post intervention at 60 minutes and 120 minutes
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20012982Radulovic M, Schilero GJ, Wecht JM, La Fountaine M, Rosado-Rivera D, Bauman WA. Exhaled nitric oxide levels are elevated in persons with tetraplegia and comparable to that in mild asthmatics. Lung. 2010 Jun;188(3):259-62. doi: 10.1007/s00408-009-9207-x. Epub 2009 Dec 15.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Miroslav Radulovic, MD principal investigator
VA Medical Center, Bronx
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing N-Nitro L-arginine-methylester (L-NAME) in people with Tetraplegia and Asthma, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Exhaled Levels of Nitric Oxide (time frame: Exhaled NO reported during visit, before intervention at baseline, post intervention at 60 minutes and 120 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00753948, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2020.