24hr Effects of Tiotropium Bromide in Tetraplegia

NCT02586649 | Completed Phase 2

• 1 other identifier: SCH-14-019
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Respiratory complications are the leading cause of death during the initial year after acute SCI, and the third leading cause of death thereafter. Complete or partial loss of respiratory muscle innervations in individuals with cervical and high thoracic injuries leads to inadequate ventilation and inability to effectively clear secretions, often prompting supportive ventilation following initial injury. Development of atelactasis, pneumonias and respiratory failure are the most common respiratory complications observed during the acute phase of injury. It is well known that a restrictive ventilatory defect, dependent upon the level and completeness of injury, is apparent in individuals with chronic cervical SCI. Respiratory functional impairment might be further compromised in these individuals, the majority of whom share many aspects of obstructive airway physiology commonly associated with asthma. The asthma-like features that individuals with chronic cervical SCI demonstrate have been hypothesized to be due to overriding cholinergic airway tone carried by intact vagal (parasympathetic) nerve fibers arising from the brainstem, whereas sympathetic innervations is interrupted at the level of the upper thoracic spinal cord. Whether airway narrowing and AHR in chronic cervical SCI is also related to chronic airway inflammation is unknown, although it is conceivable that repeated respiratory infections or, possibly, a neurogenic component, could contribute to chronic airway inflammation. Therefore, the investigators aim to assess how long-acting bronchodilator (tiotropium bromide) affects various indices of lung function, including: pulmonary function tests, levels of inflammation and cough strength across 24 hours after receiving study drug. Results will be analyzed for baseline, 1 hour, 3 hours, 20 hours and 24 hours post drug inhalation for both active medication and non-active placebo.

Conditions

Spinal Cord Injury

Keywords

tiotropium bromide

Outcome Measures

Primary Outcomes (2)

• Change in Spirometry values from baseline

  During Visit 1 (0,1 and 3 hours post-drug); Visit 2 (20 and 24 hours post-drug); Visit 3( between 14 and 21 days after visit 2- 0,1 and 3 hours post-drug); Visit 4 (following visit 3)

  Baseline,one hours post,three hours post,twenty hours post,twenty four hours post

• Change in Exhaled Nitric Oxide ( FeNO )

  During Visit 1 (0,1 and 3 hours post-drug); Visit 2 (20 and 24 hours post-drug); Visit 3( between 14 and 21 days after visit 2- 0,1 and 3 hours post-drug); Visit 4 (following visit 3)

  Baseline,one hours post,three hours post,twenty hours post,twenty four hours post

Secondary Outcomes (2)

• Change in Lung volumes ( Plethysmography )

  Baseline,one hours post,three hours post,twenty hours post,twenty four hours post

• Change in Airway Resistance by Impulse Oscillometry System (IOS)

  Baseline,one hours post,three hours post,twenty hours post,twenty four hours post

Study Arms (2)

Tiotropium Bromide group

EXPERIMENTAL

The study participants will be randomly assigned to receive Tiotropium bromide,single dose (inhalation capsule - 18 mcg) over the course of 24 hours on day one of visit 1 or during visit 3.On the day of the first scheduled visit ( visit 1 ),study participants will be asked to arrive between 12-1 pm at the pulmonary laboratory at the JJPVAMC (7A-13). Baseline blood pressure (BP) and heart rate (HR) measurements will be obtained prior to drug administration. Tiotropium bromide capsule containing active ingredients will be orally inhaled through a SPIRIVA HandiHaler. Measurements of exhaled nitric oxide, pulmonary function ( spirometry , static lung volumes and specific airway conductance) will be performed at 20 and 24 hours. The same schedule will be followed for visits 3 and 4;vists 3 and 4 will be scheduled between 14 and 21 days after visit 2.

Drug: Tiotropium Bromide; Drug: Placebo

Placebo

PLACEBO COMPARATOR

The study participants will be randomly assigned to receive placebo , single dose (inhalation capsule - 18 mcg) over the course of 24 hours on day one of visit 1 or during visit 3.On the day of the first scheduled visit ( visit 1 ),study participants will be asked to arrive between 12-1 pm at the pulmonary laboratory at the JJPVAMC (7A-13). Baseline blood pressure (BP) and heart rate (HR) measurements will be obtained prior to drug administration. Placebo capsule containing active ingredients will be orally inhaled through a SPIRIVA HandiHaler. Measurements of exhaled nitric oxide, pulmonary function ( spirometry , static lung volumes and specific airway conductance) will be performed at 20 and 24 hours. The same schedule will be followed for visits 3 and 4;vists 3 and 4 will be scheduled between 14 and 21 days after visit 2.

Drug: Tiotropium Bromide; Drug: Placebo

Interventions

Tiotropium Bromide DRUG

Tiotropium bromide is an anticholinergic used to study bronchodilatation and improvement of pulmonary function in tetraplegic patients

Also known as: Anticholinergic

Placebo; Tiotropium Bromide group

Placebo DRUG

Placebo is a non-active inhalation capsule .

Placebo; Tiotropium Bromide group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic Spinal Cord Injury (\>1 year post-injury)
• Stable tetraplegia (level of injury C3-C8, non-ventilator dependent)
• Male or female between the ages 18-65

You may not qualify if:

• Smoking, active or history of smoking during last 6 months;
• Ventilator dependent;
• Known history of asthma, COPD or inflammatory disease during lifetime;
• Active or recent (within 3 months) respiratory infection;
• Use of medications known to affect the respiratory system;
• Use of medications known to alter airway caliber
• Uncontrolled hypertension;
• Glaucoma or cataracts;
• History of milk protein allergy
• Pregnant or trying to become pregnant
• Lack of mental capacity to give informed consent

Sponsors & Collaborators

• James J. Peters Veterans Affairs Medical Center: lead

Study Sites (1)

James J Peters VA Medical Center

New York, New York, 10468, United States

Location

Related Publications (5)

• 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.

  PMID: 20012982 BACKGROUND

• DeVivo MJ, Krause JS, Lammertse DP. Recent trends in mortality and causes of death among persons with spinal cord injury. Arch Phys Med Rehabil. 1999 Nov;80(11):1411-9. doi: 10.1016/s0003-9993(99)90252-6.

  PMID: 10569435 RESULT

• Spungen AM, Dicpinigaitis PV, Almenoff PL, Bauman WA. Pulmonary obstruction in individuals with cervical spinal cord lesions unmasked by bronchodilator administration. Paraplegia. 1993 Jun;31(6):404-7. doi: 10.1038/sc.1993.67.

  PMID: 8337005 RESULT

• Almenoff PL, Alexander LR, Spungen AM, Lesser MD, Bauman WA. Bronchodilatory effects of ipratropium bromide in patients with tetraplegia. Paraplegia. 1995 May;33(5):274-7. doi: 10.1038/sc.1995.62.

  PMID: 7630654 RESULT

• Sikka N, Margolis G. Understanding diversity among prehospital care delivery systems around the world. Emerg Med Clin North Am. 2005 Feb;23(1):99-114. doi: 10.1016/j.emc.2004.09.007.

  PMID: 15663976 RESULT

MeSH Terms

Conditions

Spinal Cord Injuries

Interventions

Tiotropium Bromide; Cholinergic Antagonists

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs

Study Officials

• Gregory Schilero, MD

  James J. Peters VA Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Sleep Lab/ICU

Study Record Dates

• First Submitted: October 13, 2015
• First Posted: October 26, 2015
• Study Start: July 1, 2014
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: September 16, 2020

Record last verified: 2020-09

Locations

US (1)