24hr Effects of Tiotropium Bromide in Tetraplegia

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-07-31

Study Completion Date

2019-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

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

NCT01355991

Spinal Cord Injury

UNKNOWN PHASE1

Albuterol to Improve Respiratory Strength in SCI

NCT02508311

Spinal Cord Injury Respiratory Muscle Weakness

TERMINATED PHASE4

Diaphragm Pacing After Spinal Cord Injury

NCT02556125

Injuries, Spinal Cord

COMPLETED

Impact of Intermittent Hypoxia and Prednisolone on Motor Performance in Persons With SCI

NCT03752749

Spinal Cord Injuries

COMPLETED NA

Intermittent Hypoxia Elicits Prolonged Restoration of Motor Function in Human SCI

NCT01272349

Spinal Cord Injury

COMPLETED PHASE1

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

In addition to a restrictive ventilatory defect stemming for respiratory muscle paralysis, cervical SCI (tetraplegia) is associated with obstructive airway physiology similar to that associated with asthma. The investigators hypothesize that these aspects of obstructive physiology stem from unopposed increases in cholinergic airway tone as a result of autonomic imbalance; where vagal innervation (cholinergic neurotransmission) to the lungs is intact, and the bronchodilating adrenergic influences of sympathetic pathways are interrupted. The investigators demonstrated using spirometric criteria, significant bronchodilator responses in approximately 50% of subjects with tetraplegia following inhalation of short acting beta-2 agonists (albuterol sulfate) and anticholinergic agents (ipratropium bromide). When specific airway conductance (sGaw), a more sensitive indicator of bronchodilation, was assessed via whole body plethysmography, significant bronchodilation and restoration of normal airway caliber was noted in all subjects.

Intuitively, one might expect that through bronchodilation susceptible individuals with tetraplegia who already have compromised respiratory muscle strength and weakened cough might benefit from better airway clearance, and via increases in lung volumes improve the length-tension relationship of residual expiratory muscles for initiation of more forceful coughs. Based upon a comparative study of the bronchodilator effects of ipratropium bromide versus albuterol in persons with tetraplegia (in publication), it appears that ipratropium bromide elicited greater bronchodilation, perhaps because of the specificity of action in blocking acetylcholine binding to the muscarinic-3 (M3) airway smooth muscle receptor. The investigators purpose in this preliminary study is to assess whether salutary effects upon pulmonary function, cough strength, and airway inflammation are observed across a twenty-four hour period following inhalation of a single dose of tiotropium bromide 18 mcg inhalational capsule versus placebo utilizing a double-blind crossover design in persons with chronic stable tetraplegia.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Spinal Cord Injury

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Tiotropium Bromide group

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.

Group Type EXPERIMENTAL

Tiotropium Bromide

Intervention Type DRUG

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

Placebo

Intervention Type DRUG

Placebo is a non-active inhalation capsule .

Placebo

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.

Group Type PLACEBO_COMPARATOR

Tiotropium Bromide

Intervention Type DRUG

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

Placebo

Intervention Type DRUG

Placebo is a non-active inhalation capsule .

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Tiotropium Bromide

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

Intervention Type DRUG

Placebo

Placebo is a non-active inhalation capsule .

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Anticholinergic

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

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

Exclusion Criteria

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

Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No