Effects of Anticholinergic or Long-Acting Beta 2 Agonist on FeNO and Pulmonary Function in SCI

Study Overview
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Brief Summary
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To determine the acute and chronic effects of a short course of treatment on spinal cord injured (SCI) individuals with either an anticholinergic agent (tiotropium) or with a β₂ agonist (Salmeterol) on: Fraction of expired NO (FeNO) Selected Biomarkers of inflammation in exhaled breath condensates (EBC) Pulmonary function, as measured by pulmonary function tests and body plethysmography

Official Title
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Acute and Chronic Effects of an Anticholinergic Agent or a Long-Acting Beta 2 Agonist on Levels of Exhaled Nitric Oxide and Pulmonary Function in Persons With Tetraplegia

Conditions
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Spinal Cord Injury

Intervention / Treatment
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* Drug: Tiotropium
* Drug: Salmeterol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic Spinal Cord Injury (>1 year post-injury) All American Spinal Injury Association (ASIA) classifications Stable tetraplegia (level of injury C3-C8, non-ventilator dependent) Age 18-65 years Exclusion Criteria: Smoking, active or history of smoking within last 6 months; Active respiratory disease; Known history of asthma during lifetime or recent (within 3 months) respiratory infections; Use of medications known to affect the respiratory system; Use of medications known to alter airway caliber; Coronary heart and/or artery disease; Hypertension; Adrenal insufficiency; Pregnancy; Severe Milk Protein Allergy; Lack of mental capacity to give informed consent; Previous allergic reaction or hypersensitivity to salmeterol or tiotropium; Individuals taking medication(s) with known /potential drug interactions or suggested therapy modification for concomitant use with salmeterol or tiotropium such as: (1) selective alpha-/beta- blockers: carvedilol, labetalol; (2) non-selective beta-blockers: Carteolol; Levobunolol; Metipranolol; Nadolol; Penbutolol; Pindolol; Propranolol; Sotalol; Timolol); (3) CYP3A4 Inhibitors: (e.g, Atazanavir; Clarithromycin; Conivaptan; Darunavir; Delavirdine; Fosamprenavir; Imatinib; Indinavir; Isoniazid; Itraconazole; Ketoconazole; Lopinavir; Nefazodone; Nelfinavir; NiCARdipine; Posaconazole; QuiNIDine; Ritonavir; Saquinavir; Telithromycin; Voriconazole; (4) Iobenguane I 123 / Sympathomimetics: Albuterol; Aminophylline; Arformoterol; Armodafinil; Benzphetamine; Caffeine; Dexmethylphenidate; Dextroamphetamine; Diethylpropion; Dipivefrin; DOBUTamine; DOPamine; Doxapram; Dyphylline; EPHEDrine; EPINEPHrine; Fenoterol; Formoterol; Isometheptene; Levalbuterol; Levonordefrin; Lisdexamfetamine; Metaproterenol; Methamphetamine; Methylphenidate; Midodrine; Modafinil; Naphazoline; Norepinephrine; Oxymetazoline; Phendimetrazine; Phentermine; Phenylephrine; Pirbuterol; Propylhexedrine; Pseudoephedrine; Sibutramine; Terbutaline; Theophylline; Xylometazoline.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Anticholinergic Agent<br> | Drug: Tiotropium<br>* 18mcg/ capsule inhaled once daily for two weeks.<br>|
| Active Comparator: Long Acting Beta 2 Agonist<br> | Drug: Salmeterol<br>* 50mcg inhalation twice daily for two weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of an anticholinergic agent or beta 2 agonist on the fraction of expired NO (FeNO) | This will be a crossover trial. Baseline measurements will be taken, followed by two weeks of drug intervention (Salmeterol or Tiotropium Bromide). After two weeks the subject will return for post drug measurements. There will be a wash out period of four weeks, and then the subject will return again for the baseline measurements of drug 2, followed by two weeks of intervention and a final assessment. | Approximately 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Selected Biomarkers of inflammation(TNF-alpha,Isoprostane 8, Leukotriene B4) in exhaled breath condensates (EBC)after intervention | The subject will be randomized to receive either anticholinergic agent or long acting Beta2 agonist. Measurements of EBC will take place at baseline, 1 hr post drug administration, and two weeks after intervention. Biomarkers of inflammation will be assessed by collected exhaled breath condensates, which will subsequently be sent for biochemical analysis. Markers include Isoprostane-8, TNF-Alpha, and Leukotriene B4. | Approx. 8 weeks | 
| Pulmonary function, as measured by pulmonary function tests and body plethysmography | This will be a crossover trial. Baseline measurements will be taken, followed by two weeks of drug intervention (Salmeterol or Tiotropium Bromide). After two weeks the subject will return for post drug measurements. There will be a wash out period of four weeks, and then the subject will return again for the baseline measurements of drug 2, followed by two weeks of intervention and a final assessment. Pulmonary assessments include: Spirometry and Plethysmography. | Approx. 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Function, Spinal Cord Injury, Tetraplegia, Bronchodilator