Epi Stim to Facilitate Standing and Stepping

NCT ID: NCT02339233

Last Updated: 2022-04-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-01
• Study Completion Date: 2019-10-03

Brief Summary

The overall aim is to assess whether task specific locomotor training and spinal cord electrical stimulation (SCES) can induce neural reorganization of the functionally isolated human spinal cord to improve standing and stepping in individuals with functionally complete SCI. The investigators propose that locomotor training will result in generation of more effective standing and stepping efferent patterns by restoring phase dependent modulation of reflexes and reciprocal inhibition, reducing clonus and mediating interlimb coordination. The investigators propose that the SCES will optimize the physiological state of the spinal cord interneuronal circuitry compromised by compensating for loss of supraspinal input for the retraining of these tasks.

Detailed Description

Participants will be screened for eligibility and then participate in pre-training motor, bladder and cardiovascular experiments, followed by 80 sessions of locomotor training. Participants will repeat experiments after the 80 training sessions to quantify that no motor pattern changes are achievable with locomotor training alone and will be evaluated for appropriate candidacy for surgery and epidural stimulation. Participants will be surgically implanted with an epidural stimulator and experiments will be conducted with and without stimulation. Investigators will identify appropriate stimulation parameters for inducing stepping and standing in combination with manual assistance using body weight support on a treadmill and/or overground. Participants will undergo 80-200 training sessions of locomotor training with epidural stimulation. Experiments will be repeated mid and post-training interventions.

Conditions

Spinal Cord Injury

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Epidural Stimulator

Eligible participants will be implanted with 16-electrode epidural array in the T11-L1 area of the spinal cord

Group Type: EXPERIMENTAL

Standing and Stepping with spinal cord Epidural Stimulation

Intervention Type: DEVICE

Standing and Stepping with support from trainers as needed, overground or in a harness with body weight support on a treadmill. Epidural stimulation with specific configurations will be administered to generate standing and stepping.

Interventions

Standing and Stepping with spinal cord Epidural Stimulation

Standing and Stepping with support from trainers as needed, overground or in a harness with body weight support on a treadmill. Epidural stimulation with specific configurations will be administered to generate standing and stepping.

Intervention Type: DEVICE

Other Intervention Names

Stand-scES; Step-scES; Locomotor Training (LT)

Eligibility Criteria

Inclusion Criteria

• All research participants, irrespective of age or sex, will meet the following criteria:

• stable medical condition without cardiopulmonary disease or dysautonomia that would contraindicate standing or stepping with BWST;
• no painful musculoskeletal dysfunction, unhealed fracture, contracture, pressure sore, or urinary tract infection that might interfere with stand or step training;
• no clinically significant depression or ongoing drug abuse;
• no current anti-spasticity medication regimen;
• non-progressive SCI above T10;
• must not have received botox injections in the prior six months;
• be unable to stand or step independently;
• at least one-year post injury; and
• must be at least 18 years of age.

In addition, all subjects must satisfy each of the three conditions of the functional neurophysiological assessment described below.

• There is no descending volitional control of movement below the lesion
• Segmental reflexes remain functional below the lesion
• Brain influence on spinal reflexes is retained

Exclusion Criteria

• Ventilatory dependent
• painful musculoskeletal function, unhealed fracture, contracture, or pressure sore that might interfere with training;
• clinically significant depression or ongoing drug abuse;
• cardiovascular, respiratory, bladder or renal disease unrelated to SCI;
• severe anemia (Hgb<8 g/dL) or hypovolemia; and
• HIV or AIDS related illness.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, Los Angeles

OTHER

Sponsor Role: collaborator

Christopher Reeve Paralysis Foundation

OTHER

Sponsor Role: collaborator

Kessler Foundation

OTHER

Sponsor Role: collaborator

The Leona M. and Harry B. Helmsley Charitable Trust

OTHER

Sponsor Role: collaborator

National Institute for Biomedical Imaging and Bioengineering (NIBIB)

NIH

Sponsor Role: collaborator

University of Louisville

OTHER

Sponsor Role: lead

Responsible Party

Susan Harkema

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Susan Harkema, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Louisville

Locations

University of Louisville

Louisville, Kentucky, United States

Countries

United States

References

Herrity AN, Williams CS, Angeli CA, Harkema SJ, Hubscher CH. Lumbosacral spinal cord epidural stimulation improves voiding function after human spinal cord injury. Sci Rep. 2018 Jun 6;8(1):8688. doi: 10.1038/s41598-018-26602-2.

Reference Type: BACKGROUND

PMID: 29875362 (View on PubMed)

Mesbah S, Angeli CA, Keynton RS, El-Baz A, Harkema SJ. A novel approach for automatic visualization and activation detection of evoked potentials induced by epidural spinal cord stimulation in individuals with spinal cord injury. PLoS One. 2017 Oct 11;12(10):e0185582. doi: 10.1371/journal.pone.0185582. eCollection 2017.

Reference Type: BACKGROUND

PMID: 29020054 (View on PubMed)

Sayenko DG, Angeli C, Harkema SJ, Edgerton VR, Gerasimenko YP. Neuromodulation of evoked muscle potentials induced by epidural spinal-cord stimulation in paralyzed individuals. J Neurophysiol. 2014 Mar;111(5):1088-99. doi: 10.1152/jn.00489.2013. Epub 2013 Dec 11.

Reference Type: BACKGROUND

PMID: 24335213 (View on PubMed)

Angeli CA, Edgerton VR, Gerasimenko YP, Harkema SJ. Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans. Brain. 2014 May;137(Pt 5):1394-409. doi: 10.1093/brain/awu038. Epub 2014 Apr 8.

Reference Type: RESULT

PMID: 24713270 (View on PubMed)

Angeli CA, Boakye M, Morton RA, Vogt J, Benton K, Chen Y, Ferreira CK, Harkema SJ. Recovery of Over-Ground Walking after Chronic Motor Complete Spinal Cord Injury. N Engl J Med. 2018 Sep 27;379(13):1244-1250. doi: 10.1056/NEJMoa1803588. Epub 2018 Sep 24.

Reference Type: RESULT

PMID: 30247091 (View on PubMed)

Rejc E, Angeli CA, Atkinson D, Harkema SJ. Motor recovery after activity-based training with spinal cord epidural stimulation in a chronic motor complete paraplegic. Sci Rep. 2017 Oct 26;7(1):13476. doi: 10.1038/s41598-017-14003-w.

Reference Type: RESULT

PMID: 29074997 (View on PubMed)

Rejc E, Angeli CA, Bryant N, Harkema SJ. Effects of Stand and Step Training with Epidural Stimulation on Motor Function for Standing in Chronic Complete Paraplegics. J Neurotrauma. 2017 May 1;34(9):1787-1802. doi: 10.1089/neu.2016.4516. Epub 2016 Oct 5.

Reference Type: RESULT

PMID: 27566051 (View on PubMed)

Rejc E, Angeli C, Harkema S. Effects of Lumbosacral Spinal Cord Epidural Stimulation for Standing after Chronic Complete Paralysis in Humans. PLoS One. 2015 Jul 24;10(7):e0133998. doi: 10.1371/journal.pone.0133998. eCollection 2015.

Reference Type: RESULT

PMID: 26207623 (View on PubMed)

Harkema S, Gerasimenko Y, Hodes J, Burdick J, Angeli C, Chen Y, Ferreira C, Willhite A, Rejc E, Grossman RG, Edgerton VR. Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study. Lancet. 2011 Jun 4;377(9781):1938-47. doi: 10.1016/S0140-6736(11)60547-3. Epub 2011 May 19.

Reference Type: RESULT

PMID: 21601270 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Informed Consent Form

View Document

Other Identifiers

5R01EB007615

Identifier Type: NIH

Identifier Source: secondary_id

View Link

07.0066 Epi Stim

Identifier Type: -

Identifier Source: org_study_id