Epi Stim to Facilitate Standing and Stepping

• Sponsor: University of Louisville (Other)
• Overall Status: Completed
• CT.gov ID: NCT02339233
• Collaborator: University of California, Los Angeles (Other), Christopher Reeve Paralysis Foundation (Other), Kessler Foundation (Other), The Leona M. and Harry B. Helmsley Charitable Trust (Other), National Institute for Biomedical Imaging and Bioengineering (NIBIB) (NIH)
• Enrollment: 8
• Location: 1
• Arm: 1
• Actual Duration (Months): 117
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Spinal Cord Injury	Device: Standing and Stepping with spinal cord Epidural Stimulation	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Spinal Epidural Electrode Array to Facilitate Standing and Stepping After Spinal Cord Injury
• Actual Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Oct 3, 2019
• Actual Study Completion Date: Oct 3, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Epidural Stimulator Eligible participants will be implanted with 16-electrode epidural array in the T11-L1 area of the spinal cord	Device: 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.; Other Names: Stand-scES Step-scES Locomotor Training (LT)

Outcome Measures

Primary Outcome Measures

1. Change From Baseline of Lower Extremity Independence Time During 10 Min Standing Bout After 160 Sessions (1 Year) [Baseline, 160 sessions (1 year)]

   We will measure the amount of time individuals are able to stand without manual assistance (independently) throughout a 10 min bout

2. Change From Baseline of Stepping Independence Time During 6 Min Stepping Bout After 160 Sessions (1 Year) [Baseline, 160 session (1 year)]

   We will measure the number of steps individuals are able to take without manual assistance (independently) throughout a 6 min stepping bout

Secondary Outcome Measures

1. Change From Baseline of Number of Consecutive Hip Flexion Repetitions Performed Within One Minute After 160 Sessions (1 Year) [Baseline, 160 sessions (1 year)]

   We will measure the ability of the individuals to perform consecutive hip flexion repetitions with stimulation during a 1 minute period

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Louisville	Louisville	Kentucky	United States	40202

Sponsors and Collaborators

• University of Louisville
• University of California, Los Angeles
• Christopher Reeve Paralysis Foundation
• Kessler Foundation
• The Leona M. and Harry B. Helmsley Charitable Trust
• National Institute for Biomedical Imaging and Bioengineering (NIBIB)

Investigators

• Principal Investigator: Susan Harkema, PhD, University of Louisville

Study Documents (Full-Text)

• Study Protocol and Informed Consent Form - Apr 19, 2018

More Information

Publications

• 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.
• 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.
• 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. Erratum in: J Neurophysiol. 2015 Jan 15;113(2):678.

• Responsible Party: Susan Harkema, Professor, University of Louisville
• ClinicalTrials.gov Identifier: NCT02339233
• Other Study ID Numbers: 07.0066 Epi Stim; 5R01EB007615
• First Posted: Jan 15, 2015
• Last Update Posted: Apr 22, 2022
• Last Verified: Apr 1, 2022

• Keywords provided by Susan Harkema, Professor, University of Louisville: Epidural Stimulation
• Additional relevant MeSH terms: Spinal Cord Injuries

Study Results

Participant Flow

Arm/Group Title	Epidural Stimulator
Arm/Group Description	Eligible participants will be implanted with 16-electrode epidural array in the T11-L1 area of the spinal cord 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.
Period Title: Overall Study
STARTED	8
COMPLETED	8
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Epidural Stimulator
Arm/Group Description	Eligible participants will be implanted with 16-electrode epidural array in the T11-L1 area of the spinal cord 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.
Overall Participants	8
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	8 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	1 12.5%
Male	7 87.5%
Race and Ethnicity Not Collected (Count of Participants)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline of Lower Extremity Independence Time During 10 Min Standing Bout After 160 Sessions (1 Year)
Description	We will measure the amount of time individuals are able to stand without manual assistance (independently) throughout a 10 min bout
Time Frame	Baseline, 160 sessions (1 year)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Epidural Stimulator
Arm/Group Description	Eligible participants will be implanted with 16-electrode epidural array in the T11-L1 area of the spinal cord 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.
Measure Participants	8
Mean (Standard Deviation) [minutes]	40.6 (30.2)

2. Primary Outcome

Title	Change From Baseline of Stepping Independence Time During 6 Min Stepping Bout After 160 Sessions (1 Year)
Description	We will measure the number of steps individuals are able to take without manual assistance (independently) throughout a 6 min stepping bout
Time Frame	Baseline, 160 session (1 year)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Epidural Stimulator
Arm/Group Description	Eligible participants will be implanted with 16-electrode epidural array in the T11-L1 area of the spinal cord 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.
Measure Participants	8
Mean (Standard Deviation) [steps]	197.13 (421.89)

3. Secondary Outcome

Title	Change From Baseline of Number of Consecutive Hip Flexion Repetitions Performed Within One Minute After 160 Sessions (1 Year)
Description	We will measure the ability of the individuals to perform consecutive hip flexion repetitions with stimulation during a 1 minute period
Time Frame	Baseline, 160 sessions (1 year)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Epidural Stimulator
Arm/Group Description	Eligible participants will be implanted with 16-electrode epidural array in the T11-L1 area of the spinal cord 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.
Measure Participants	8
Mean (Standard Deviation) [Repetitions]	14.25 (9.8)

Adverse Events

Time Frame	From implant through the end of the second intervention, an average of one year.
Arm/Group Title	Epidural Stimulator
Arm/Group Description	Eligible participants will be implanted with 16-electrode epidural array in the T11-L1 area of the spinal cord 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.
All Cause Mortality
	Epidural Stimulator
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Serious Adverse Events
	Epidural Stimulator
	Affected / at Risk (%)	# Events
Total	2/8 (25%)
Musculoskeletal and connective tissue disorders
Hip Fracture	1/8 (12.5%)	1
Surgical and medical procedures
Device Malfunction	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	Epidural Stimulator
	Affected / at Risk (%)	# Events
Total	5/8 (62.5%)
Musculoskeletal and connective tissue disorders
Muscle Strain	1/8 (12.5%)	1
Right Ankle Edema	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
Incision Site Drainage	1/8 (12.5%)	1
Surgical and medical procedures
Flipped Stimulator	1/8 (12.5%)	1
Electrode Malfunction	1/8 (12.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.