Clinical trial NCT02339233: Epi Stim to Facilitate Standing and Stepping
Official title: Spinal Epidural Electrode Array to Facilitate Standing and Stepping After Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Spinal Cord Injury
Keywords: Epidural Stimulation
Lead sponsor: University of Louisville
Sponsor class: OTHER
Collaborators: name: University of California, Los Angeles
name: Christopher Reeve Paralysis Foundation
name: Kessler Foundation
name: The Leona M. and Harry B. Helmsley Charitable Trust
name: National Institute for Biomedical Imaging and Bioengineering (NIBIB)
First posted: 2015-01-15
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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.

Functional Neurophysiological Assessment (FNPA). We will use FNPA to screen potential research participants based on specific neurophysiological inclusion criteria. Participants must have no volitional control of movement below the level of the lesion, but must retain some brain influence on spinal reflexes. Our target population, which will be identified by FNPA, cannot be identified reliable using traditional assessments: hence individual subjects may be classified widely as Class A, B, or C on the ASIA SCI scale. We will include only subjects who fulfill the following three requirements:

* 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.

Primary outcomes:
measure: Change From Baseline of Lower Extremity Independence Time During 10 Min Standing Bout After 160 Sessions (1 Year)
timeFrame: Baseline, 160 sessions (1 year)
measure: Change From Baseline of Stepping Independence Time During 6 Min Stepping Bout After 160 Sessions (1 Year)
timeFrame: Baseline, 160 session (1 year)
Secondary outcomes:
measure: Change From Baseline of Number of Consecutive Hip Flexion Repetitions Performed Within One Minute After 160 Sessions (1 Year)
timeFrame: Baseline, 160 sessions (1 year)
Other outcomes:
Locations:
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
Study officials:
affiliation: University of Louisville
name: Susan Harkema, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.