Diaphragm Pacing After Spinal Cord Injury

NCT02556125 | Completed

• 1 other identifier: IRB201500402
• Study Type: observational
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

Respiratory dysfunction is the leading cause of death in individuals with spinal cord injuries (SCIs). Nearly one quarter of all SCI cases involve injury to the upper spinal cord segments which impairs neural activation of the diaphragm muscle and compromises breathing. Although mechanical ventilation can be life-saving after cervical SCI (C-SCI), it also triggers rapid and profound diaphragm muscle atrophy, thereby complicating (or even preventing) ventilator weaning. Intramuscular diaphragm stimulation, or diaphragm pacing, was developed to replace long-term ventilator support, and is now used acutely post C-SCI (\<4 months following injury) to promote ventilator weaning. The impact of diaphragm pacing on respiratory function and diaphragm muscle activation has not been formally evaluated. This is an essential step in determining the efficacy of intramuscular diaphragm stimulation and its effects on respiratory function after SCI. Accordingly, this research study will evaluate the effects of intramuscular diaphragm stimulation and test the hypothesis that diaphragm pacing enhances neuromuscular diaphragm activation and respiratory function in adults with cervical SCIs. The investigators will test the hypothesis by evaluating the effects of diaphragm pacing on neuromuscular activation of the diaphragm by directly recording electromyogram (EMG) activity from the intramuscular pacing electrodes. Recording from these surgically-implanted electrodes allows direct comparisons of EMG activity across time, minimizing methodological limitations inherent with surface or percutaneous EMG recordings. This approach, in association with respiratory assessments, will be used to investigate the impact of diaphragm pacing in adults with intramuscular diaphragm pacing electrodes following acute, traumatic C-SCIs.

Conditions

Injuries, Spinal Cord

Keywords

SCI; Respiratory impairment; Diaphragm pacing; Diaphragm stimulation

Outcome Measures

Primary Outcomes (6)

• Electromyogram (EMG) will be used to assess the neuromuscular activation of the diaphragm

  Neuromuscular activation of the diaphragm will be assessed by recording diaphragm EMGs from the surgically-implanted intramuscular stimulating electrodes. This approach will allow for comparisons of EMG recordings across time. EMGs will be recorded during non-stimulated respiration (diaphragm pacer turned off) and simultaneously with assessments of respiratory function. A Friedman's ANOVA will be used to test for differences in the EMG outcomes across the multiple (4 or more) time points. Post-hoc comparisons will be conducted using a Wilcoxon signed-rank test.

  Change in baseline to months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12

• Maximal inspiratory pressure will be used to assess diaphragm strength

  Respiratory function will be assessed using standard clinical approaches to measure inspiratory and expiratory pressures and volumes as well as standard spirometry. A Friedman's ANOVA will be used to test for differences in the respiratory outcomes across the multiple (4 or more) time points. Post-hoc comparisons will be conducted using a Wilcoxon signed-rank test.

  Change in baseline to months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12

• Sniff nasal inspiratory pressure may be used to assess diaphragm strength

  Respiratory function will be assessed using standard clinical approaches to measure inspiratory and expiratory pressures and volumes as well as standard spirometry. A Friedman's ANOVA will be used to test for differences in the respiratory outcomes across the multiple (4 or more) time points. Post-hoc comparisons will be conducted using a Wilcoxon signed-rank test.

  Change in baseline to months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12

• Maximal expiratory pressure will be used to assess respiratory function

  Respiratory function will be assessed using standard clinical approaches to measure inspiratory and expiratory pressures and volumes as well as standard spirometry. A Friedman's ANOVA will be used to test for differences in the respiratory outcomes across the multiple (4 or more) time points. Post-hoc comparisons will be conducted using a Wilcoxon signed-rank test.

  Change in baseline to months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12

• Spirometry and flow volume curves/loops will be used to assess respiratory function at rest

  Respiratory function will be assessed using standard clinical approaches to measure inspiratory and expiratory pressures and volumes as well as standard spirometry. A Friedman's ANOVA will be used to test for differences in the respiratory outcomes across the multiple (4 or more) time points. Post-hoc comparisons will be conducted using a Wilcoxon signed-rank test.

  Change in baseline to months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12

• Spirometry and forced flow volume curves/loops will be used to assess respiratory function at maximal effort

  Respiratory function will be assessed using standard clinical approaches to measure inspiratory and expiratory pressures and volumes as well as standard spirometry. A Friedman's ANOVA will be used to test for differences in the respiratory outcomes across the multiple (4 or more) time points. Post-hoc comparisons will be conducted using a Wilcoxon signed-rank test.

  Change in baseline to months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12

Secondary Outcomes (1)

• American Spinal Cord Injury (ASIA) Impairment Scale

  Change in baseline to months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12

Study Arms (1)

Cervical SCI

Participants with acute, traumatic cervical spinal cord injuries (C-SCIs), classified according to the American Spinal Injury Association (ASIA) Impairment Scale (AIS) as A-C (complete SCI (A); motor complete SCI (B); motor incomplete with minimal motor function (C)), affecting C1-C6 spinal cord segments, and who have been scheduled to undergo implantation of a diaphragm pacer, or who have recently received (in past 5-days) implantation of intramuscular diaphragm pacing electrodes due to severe respiratory impairments and dependence on mechanical ventilation.

Device: Diaphragm pacing

Interventions

Diaphragm pacing DEVICE

Intramuscular diaphragm implantation is achieved by a laparoscopic approach whereby phrenic motor points on the diaphragm are mapped to optimize electrode placement. The electrodes are threaded into the diaphragm muscle and wire leads are externalized and attached to a stimulation controller.

Cervical SCI

Eligibility Criteria

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

Study Population

Forty adults will be recruited from an acute care hospital setting

You may qualify if:

• Acute, traumatic cervical spinal cord injuries (C-SCIs), classified according to the American Spinal Injury Association (ASIA) Impairment Scale (AIS) as A-C (complete SCI (A); motor complete SCI (B); motor incomplete with minimal motor function (C)), affecting C1-C6 spinal cord segments
• Scheduled to undergo implantation of a diaphragm pacer, or who have recently received (in past 5-days) implantation of intramuscular diaphragm pacing electrodes due to severe respiratory impairments and dependence on mechanical ventilation.

You may not qualify if:

• Progressive neuromuscular diseases such as multiple sclerosis and myasthenia gravis
• History of neurologic injuries such as stroke or prior SCI
• Chest wall injuries or deformities likely to influence breathing
• Pulmonary infection
• Pregnancy
• Cognitive impairments limiting study participation

Sponsors & Collaborators

• University of Florida: lead
• Brooks Rehabilitation: collaborator
• The Craig H. Neilsen Foundation: collaborator

Study Sites (2)

University of Florida

Gainesville, Florida, 32610, United States

Location

Brooks Rehabilitation

Jacksonville, Florida, 32216, United States

Location

Related Publications (6)

• Posluszny JA Jr, Onders R, Kerwin AJ, Weinstein MS, Stein DM, Knight J, Lottenberg L, Cheatham ML, Khansarinia S, Dayal S, Byers PM, Diebel L. Multicenter review of diaphragm pacing in spinal cord injury: successful not only in weaning from ventilators but also in bridging to independent respiration. J Trauma Acute Care Surg. 2014 Feb;76(2):303-9; discussion 309-10. doi: 10.1097/TA.0000000000000112.

  PMID: 24458038 BACKGROUND

• Onders RP, Elmo M, Kaplan C, Katirji B, Schilz R. Extended use of diaphragm pacing in patients with unilateral or bilateral diaphragm dysfunction: a new therapeutic option. Surgery. 2014 Oct;156(4):776-84. doi: 10.1016/j.surg.2014.07.021.

  PMID: 25239317 BACKGROUND

• Romero FJ, Gambarrutta C, Garcia-Forcada A, Marin MA, Diaz de la Lastra E, Paz F, Fernandez-Dorado MT, Mazaira J. Long-term evaluation of phrenic nerve pacing for respiratory failure due to high cervical spinal cord injury. Spinal Cord. 2012 Dec;50(12):895-8. doi: 10.1038/sc.2012.74. Epub 2012 Jul 10.

  PMID: 22777487 BACKGROUND

• Hirschfeld S, Exner G, Luukkaala T, Baer GA. Mechanical ventilation or phrenic nerve stimulation for treatment of spinal cord injury-induced respiratory insufficiency. Spinal Cord. 2008 Nov;46(11):738-42. doi: 10.1038/sc.2008.43. Epub 2008 May 13.

  PMID: 18475279 BACKGROUND

• Onders RP, Khansarinia S, Weiser T, Chin C, Hungness E, Soper N, Dehoyos A, Cole T, Ducko C. Multicenter analysis of diaphragm pacing in tetraplegics with cardiac pacemakers: positive implications for ventilator weaning in intensive care units. Surgery. 2010 Oct;148(4):893-7; discussion 897-8. doi: 10.1016/j.surg.2010.07.008. Epub 2010 Aug 24.

  PMID: 20797750 BACKGROUND

• DiMarco AF, Onders RP, Kowalski KE, Miller ME, Ferek S, Mortimer JT. Phrenic nerve pacing in a tetraplegic patient via intramuscular diaphragm electrodes. Am J Respir Crit Care Med. 2002 Dec 15;166(12 Pt 1):1604-6. doi: 10.1164/rccm.200203-175CR.

  PMID: 12471076 BACKGROUND

MeSH Terms

Conditions

Spinal Cord Injuries; Respiratory Insufficiency

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Respiration Disorders; Respiratory Tract Diseases

Study Officials

• Emily J Fox, PT, DPT, PhD

  University of Florida; Brooks Rehabilitation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2015
• First Posted: September 22, 2015
• Study Start: December 1, 2015
• Primary Completion: August 11, 2020
• Study Completion: August 11, 2020
• Last Updated: August 13, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)