Albuterol to Improve Respiratory Strength in SCI

The Effect of an Oral Beta-2 Agonist on Respiratory Muscle Strength in SCI

Spinal cord injury (SCI), especially involving the cervical and upper thoracic segments, can significantly compromise respiratory muscle function. Respiratory complications can ensue, including lung collapse and pneumonia, which are the primary cause for mortality in association with traumatic SCI both during the acute and chronic phases post-injury. Lesions at the level of the cervical or high thoracic spinal cord result in respiratory muscle weakness, which is associated with ineffective cough, mucus retention, and mucus plugging. Despite the fact that pulmonary complications are a major cause of morbidity and mortality in this population, there is a paucity of effective interventions in the SCI population known to improve respiratory muscle strength with pharmacologic interventions receiving little to no attention. The current objective of this study is to determine the effectiveness of 16 weeks of sustained release oral Albuterol to; (1) improve respiratory muscular strength, and (2) improve cough effectiveness.

Study Overview

• Status: Terminated
• Conditions: Spinal Cord Injury; Respiratory Muscle Weakness
• Intervention / Treatment: Drug: Oral Albuterol Extended Release; Drug: Placebo

Detailed Description

Although the past 40 years has witnessed a substantial improvement in the acute and chronic management of persons with SCI, mortality remains high during the first year post-injury, and pulmonary complications including pneumonia, lung collapse (atelectasis), respiratory failure, and thromboembolism are the predominant cause. The propensity for pulmonary complications among subjects with SCI stems from paralysis of respiratory muscles. Injury to the cervical and upper thoracic cord significantly compromises function of the diaphragm, intercostal muscles, accessory respiratory muscles, and abdominal muscles. Respiratory muscle dysfunction is manifest as diminution in lung volumes, reduction in maximal static inspiratory and expiratory mouth pressures (MIP and MEP, respectively), and reduction in peak cough pressure and flow. Cough effectiveness is contingent upon both inspiratory and expiratory muscle strength; increasing the pressure-generating capacity of the inspiratory and expiratory muscles in persons with tetraplegia and high paraplegia may, therefore, translate to improved cough effectiveness and reduction in the propensity for atelectasis and, possibly, pneumonia.

Respiratory muscle training, often utilizing simple hand-held portable resistive or threshold training devices, appears to have marginal effects on vital capacity and maximal static mouth inspiratory and expiratory pressures (MIP and MEP, respectively), although data is inconclusive. Pharmacologic interventions to improve respiratory muscle strength have received little attention in the SCI population. Studies involving oral beta-2 adrenergic agonists, which have been shown to elicit anabolic effects on skeletal muscle in young men and an increase in muscle strength among patients with facioscapulohumeral muscular dystrophy, have also demonstrated salutary effects in persons with SCI. There are many foreseeable advantages of a pharmacologic approach to improve respiratory muscle strength in persons with SCI. For instance, RMT can be physically demanding and time consuming, compliance can be an issue, and sustainable improvements have not been realized. The intent in the present proposal is to enroll a targeted cohort of 24 comparatively weaker subjects with tetraplegia and high paraplegia in a randomized, double-blind, placebo-controlled, parallel group trial to assess the effects of an oral beta-2 agonist upon respiratory muscle strength and cough effectiveness.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10468
      • James J. Peters VA Medical Center, Bronx, NY

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or Female age 18 to 80
• Chronic spinal cord injury ( 1 year since injury)
• Neurological level of injury between C3-C8 (Tetraplegia)
• Neurological level of injury between T1-T6 (High Paraplegia)
• Males with maximal inspiratory pressure (MIP) < 90 cm H2O or
• Females with maximal inspiratory pressure (MIP) < 65 cm H2O

Exclusion Criteria:

• Smoking, active or history of smoking with the past year
• Ventilator Dependence
• History of blast injuries to the chest
• Antidepressant use
• History of asthma
• Active respiratory disease or recent(within 3 months) respiratory infections
• Uncontrolled hypertension or cardiovascular disease
• Current use a beta-2 adrenergic agonists
• History of epilepsy or seizure disorder
• Hyperthyroidism
• Currently taking corticosteroids
• Currently taking monoamine oxidase inhibitors or tricyclic antidepressants
• Hypersensitivity to albuterol or any of its' constituents
• Pregnant

• Use or are suspected of using over-the counter supplements or prescribed medications with anabolic characteristics (promotes improvements to muscle mass and strength) including, but not limited to:

  • creatine monohydrate
  • anabolic steroids (e.g., testosterone)
  • growth hormone
  • substances with similar actions or indications as those listed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Oral Beta-2; Subjects will receive 16 weeks of active medication.	Drug: Oral Albuterol Extended Release; Subjects will receive extended release Albuterol, 4mg twice daily for the first week. The remaining 15 weeks subjects will receive extended release Albuterol, 8mg twice daily.; Other Names: VoSpire
Placebo Comparator: Placebo; Subjects will receive 16 weeks of placebo medication.	Drug: Placebo; Subjects will receive placebo tablets twice daily for 16 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Respiratory Muscle Strength	Respiratory muscle strength will be determined by maximal inspiratory pressure and maximal expiratory pressure at the mouth during baseline visit, week 16 visit and week 18 visit.	Baseline, Week 16, Week 18

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Greg Schilero, MD, James J. Peters Veterans Affairs Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): March 2, 2022
• Study Completion (Actual): February 28, 2023

Study Registration Dates

• First Submitted: July 15, 2015
• First Submitted That Met QC Criteria: July 22, 2015
• First Posted (Estimated): July 24, 2015

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Tetraplegia; High Paraplegia
• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Wounds and Injuries; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Trauma, Nervous System; Spinal Cord Diseases; Muscle Weakness; Spinal Cord Injuries; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol
• Other Study ID Numbers: B1910-P; SCH-15-011 (Other Identifier: James J. Peters Veterans Affairs Medical Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD data is not available at this time.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No