ClinicalTrials.gov
ClinicalTrials.gov Menu

Exhaled Breath Condensate Biomarkers of Inflammation in Individuals With Chronic Cervical Spinal Cord Injury

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: NCT02235714
Recruitment Status : Completed
First Posted : September 10, 2014
Last Update Posted : September 10, 2014
Sponsor:
Information provided by (Responsible Party):
Miroslav Radulovic, M.D., James J. Peters Veterans Affairs Medical Center

Brief Summary:
The purpose of this study is to obtain markers of airway inflammation from the exhaled breath condensate (the moisture in exhaled air) for comparison to blood based markers. These markers will be compared in tetraplegic, asthmatic and able-bodied control groups. Additionally, lung function testing will be performed, and the associations between breath condensate and blood markers and pulmonary function explored between groups.

Condition or disease
Tetraplegia Asthma

Detailed Description:

The predominant mechanism for pulmonary dysfunction in individuals with chronic tetraplegia is respiratory muscle paralysis. This leads to inadequate ventilation and inability to clear secretions placing these patients at a greater risk for the development of respiratory complications. Furthermore, individuals with chronic tetraplegia exhibit baseline increases in airway tone (bronchoconstriction), restoration of normal airway caliber following bronchodilator administration, and non-specific airway hyperresponsiveness (AHR) following inhalation of methacholine, histamine, an aerosolized distilled water. These findings in persons with spinal cord injury (SCI) represent pulmonary features commonly seen in individuals with asthma. Alternatively, airway inflammation may play a role in the obstructive physiology observed in individuals with tetraplegia. In this population, identification of cellular inflammation would confirm the presence of underlying inflammation with a sputum induction. However, this method is hard to perform due to an impaired cough.

The emerging field of exhaled breath condensate (EBC) biomarkers of inflammation offers a non-invasive technique to define the presence of, and potentially address the contributing factors of airway inflammation in the respiratory tract of individuals with tetraplegia. It is thought that EBC composition reflects biochemical changes of airway lining fluid. EBC contains a large number of mediators, including adenosine, ammonia, hydrogen peroxide (H2O2), isoprostanes, leukotrienes, prostanoids, peptides and cytokines. Looking at exhaled breath profiles of various biomarkers may be used to differentiate their different pathophysiological mechanism of inflammation. In addition, measurements of some chemokines (TNF-ά, interleukin (IL)-6) and inflammatory biomarkers (LTB4) in EBC and blood simultaneously may help differentiate the degree of local vs. systemic inflammation. Understanding the underlying mechanisms involved in pulmonary dysfunction observed in persons with chronic cervical SCI may identify treatment options, such as use of inhaled steroids. This approach would be expected to ultimately improve quality of life in affected individuals, decreasing the rate of re-hospitalizations due to respiratory complications and the socioeconomic burden placed on these with SCI and the health care system.


Study Type : Observational
Actual Enrollment : 36 participants
Observational Model: Case Control
Time Perspective: Prospective
Official Title: Exhaled Breath Condensate Biomarkers of Inflammation in Individuals With Chronic Cervical Spinal Cord Injury
Study Start Date : July 2009
Actual Primary Completion Date : April 2011
Actual Study Completion Date : April 2012

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Group/Cohort
Tetraplegia
Individuals with chronic tetraplegia
Asthma
Individuals with mild asthma
Able-bodied controls
Age matched able-bodied (AB) controls with no history of lung disease



Primary Outcome Measures :
  1. Levels of inflammatory biomarkers [ Time Frame: Baseline ]
    To compare the levels of inflammatory biomarkers in exhaled breath condensate (breath condensate acidity, 8-isoprostane, LTB4, prostaglandin E2, IL-6, TNF-ά in individuals with tetraplegia to that of matched control subjects diagnosed with asthma (positive control) and healthy able-bodied individuals (negative controls).


Biospecimen Retention:   Samples Without DNA
Exhaled Breath Condensate Blood Serum


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.


Ages Eligible for Study:   18 Years to 89 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
  1. Chronic stable tetraplegia (duration of injury > 1 year) matched for age, gender, and BMI with healthy control subjects, and clinically stable mild asthmatic subjects. The subjects approached will have already consented to, or be actively participating in "Effects of Nitric Oxide Synthase Inhibitor on Levels of Exhaled NO and Airway Tone in Subjects with Chronic Cervical Spinal Cord Injury" study.
  2. Clinically stable mild asthmatic subjects (as defined by NIH asthma guidelines) [51].
  3. Healthy able-bodied individuals.
Criteria

Inclusion Criteria:

(1) 18 to 65 years old.

Groups:

  1. Chronic stable tetraplegia (duration of injury > 1 year) matched for age, gender, and BMI with healthy control subjects, and clinically stable mild asthmatic subjects. The subjects approached will have already consented to, or be actively participating in "Effects of Nitric Oxide Synthase Inhibitor on Levels of Exhaled NO and Airway Tone in Subjects with Chronic Cervical Spinal Cord Injury" study.
  2. Clinically stable mild asthmatic subjects (as defined by NIH asthma guidelines) [51].
  3. Healthy able-bodied individuals.

Exclusion criteria (all subjects):

  1. Smoking, active or history of smoking during life time.
  2. More than mild airflow obstruction as per spirometric indices,
  3. Active respiratory disease,
  4. Medications known to affect the respiratory system,
  5. Pregnancy and
  6. Lack of mental capacity to give informed consent.
  7. No history of asthma diagnosis during lifetime (able bodied and tetraplegia groups), or recent (within 3 months) respiratory infection for all groups.
  8. Receiving medications known to alter airway caliber.

Exclusion Criteria (specific to Asthmatic subjects):

  1. Moderate to severe airflow obstruction as per spirometric indices,
  2. Testing within 48 hours of last administration of long-acting inhaled bronchodilator medication,
  3. Testing within 7 days of last administration of inhaled or oral corticosteroid medication,
  4. Testing within 24 hours since last administration of leukotriene modifiers and
  5. Testing within 8 hours of last administration of a short-acting inhaled bronchodilator medications

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): NCT02235714


Locations
United States, New York
James J. Peters VA Medical Center
Bronx, New York, United States, 10468
Sponsors and Collaborators
James J. Peters Veterans Affairs Medical Center
Investigators
Principal Investigator: Miroslav Radulovic, MD James J. Peters Veterans Affairs Medical Center

Responsible Party: Miroslav Radulovic, M.D., Staff Physician, James J. Peters Veterans Affairs Medical Center
ClinicalTrials.gov Identifier: NCT02235714     History of Changes
Other Study ID Numbers: RAD-09-031
First Posted: September 10, 2014    Key Record Dates
Last Update Posted: September 10, 2014
Last Verified: September 2014

Keywords provided by Miroslav Radulovic, M.D., James J. Peters Veterans Affairs Medical Center:
Airway inflammation
Tetraplegia
Asthma
Exhaled breath condensate
Spirometry
Pulmonary Function Testing

Additional relevant MeSH terms:
Central Nervous System Diseases
Inflammation
Spinal Cord Injuries
Quadriplegia
Pathologic Processes
Spinal Cord Diseases
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries
Paralysis
Neurologic Manifestations
Signs and Symptoms