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

Phase 1

• Conditions: Spinal Cord Injury
• Interventions: Drug: Tiotropium; Drug: Salmeterol

• Registration Number: NCT01355991
• Lead Sponsor: James J. Peters Veterans Affairs Medical Center

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-05-12
• Study First Submitted QC: 2011-05-17
• Study First Posted: 2011-05-19
• Study Start: 2011-08
• Status Verified: 2015-10
• Last Update Submitted: 2015-10-22
• Last Update Posted: 2015-10-23
• Primary Completion: 2016-03
• Study Completion: 2016-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Chronic Spinal Cord Injury (>1 year post-injury)
2. All American Spinal Injury Association (ASIA) classifications
3. Stable tetraplegia (level of injury C3-C8, non-ventilator dependent)
4. Age 18-65 years

Exclusion Criteria

1. Smoking, active or history of smoking within last 6 months;
2. Active respiratory disease;
3. Known history of asthma during lifetime or recent (within 3 months) respiratory infections;
4. Use of medications known to affect the respiratory system;
5. Use of medications known to alter airway caliber;
6. Coronary heart and/or artery disease;
7. Hypertension;
8. Adrenal insufficiency;
9. Pregnancy;
10. Severe Milk Protein Allergy;
11. Lack of mental capacity to give informed consent;
12. Previous allergic reaction or hypersensitivity to salmeterol or tiotropium;
13. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Anticholinergic Agent	Tiotropium	-
Long Acting Beta 2 Agonist	Salmeterol	-

Primary Outcome Measures

Name	Time	Method
The effect of an anticholinergic agent or beta 2 agonist on the fraction of expired NO (FeNO)	Approximately 8 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Selected Biomarkers of inflammation(TNF-alpha,Isoprostane 8, Leukotriene B4) in exhaled breath condensates (EBC)after intervention	Approx. 8 weeks	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.
Pulmonary function, as measured by pulmonary function tests and body plethysmography	Approx. 8 weeks	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.

Trial Locations

Locations (2)

Kessler Institute for Rehabilitation; 🇺🇸 West Orange, New Jersey, United States

James J. Peters VA Medical Center; 🇺🇸 Bronx, New York, United States