Multimodal Exercises to Improve Leg Function After Spinal Cord Injury

A Hebbian Approach to Regaining Control of Spared Circuits in Spinal Cord Injury

Many people with spinal cord injury (SCI) retain at least some movement below their injury, but their muscles often have a 'mind of their own'. Typical exercise programs focus on keeping muscles strong and flexible, but don't usually focus on helping patients control their muscles. The investigators' exercise research study will compare two different programs with the specific goal of improving conscious control of patients' muscles below the injury. This study focuses on those with 'chronic' SCI - the injury occurred at least one year prior to enrolling.

This is a single center study taking place in the Bronx, NY.

The first phase of the study will be observational - the investigators will analyze which nerve connections might remain partially intact through the injury (even if the nerves aren't consciously controlled). Participants with all severity of SCI may participate in this first phase.

The second phase of the study will involve people who retain at least slight ability to move their legs and the ability to move the arms against gravity. Each person will undergo two different exercise rehabilitation strategies: weight-supported treadmill training; and balance training combined with skilled arm or hand exercises.

The investigators will compare the effects of these exercise programs on a variety of outcomes, including gait speed, balance, strength, and muscle activation in response to brain stimulation.

The investigators hypothesize that participants with chronic SCI undergoing combined balance/arm/hand training will show improved outcomes when compared to traditional gait or balance training.

Study Overview

• Status: Completed
• Conditions: Spinal Cord Injuries; Paraparesis; Paraplegia
• Intervention / Treatment: Device: Robotic body weight supported treadmill training; Other: Harness-supported multimodal balance training

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

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: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males or females age 21-65 years;
• SCI duration > 12 months;
• SCI level C2-T12;
• All SCI severity eligible for baseline testing;
• For exercise protocol, must have severity of Grade C or D on American Spinal Injury Association (ASIA) Impairment Scale, or volitional strength of at least 1/5 in two or more key lower extremity muscles, as well as at least 3/5 in both shoulder and elbow muscles;
• Able to tolerate upright position with support;
• Morphologically capable of fitting a weight-support harness and robotic treadmill system;
• Ability to give informed consent.

Exclusion Criteria:

• Unsuitable cognitive capacity as judged by the study physician;
• Diagnosis of neurological injury other than SCI, such as stroke, traumatic brain injury, or other neurological condition that the study physician considers to be exclusionary;
• Multiple spinal cord lesions;
• History of frequent autonomic dysreflexia;
• History of seizures;
• Use of medications that significantly lower seizure threshold, such as anti-psychotics, tricyclic antidepressants, amphetamines, and bupropion;
• History of implanted brain/spine/nerve stimulators, aneurysm clips, or cardiac pacemaker/defibrillator;
• Deep vein thrombosis in lower extremities of less than 6 months duration;
• Pregnancy;
• (Interventional phase only): Lack of detectable tibialis anterior motor evoked potential (MEP) at baseline even with active facilitation;
• (Interventional phase only): Pressure ulcers greater than stage 1 severity on the foot, ankle, knee and/or pelvic girdle;
• (Interventional phase only): Bone mineral density of the hip (proximal femur) T-score <3.5 standard deviations from age- and gender-matched normative data;
• (Interventional phase only): Any spasticity, contractures, or heterotopic ossification that result in inadequate range of motion of the shoulder, elbow, wrist, fingers, hip, knee, or ankle joints in the judgment of the study physician;
• (Interventional phase only): Inability to cooperate with instructions or unwilling to commit to daily training sessions for 3-4 days per week over 12-16 weeks;
• (Interventional phase only): A diagnosis of coronary artery disease that precludes moderate to intense exercise.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Multimodal then Treadmill training; Participants will undergo harness-supported multimodal balance training exercises while simultaneously performing skilled hand exercises. Following a washout period of at least 6 weeks, Participants will undergo body weight supported treadmill training using the Lokomat apparatus.	Device: Robotic body weight supported treadmill training; 30-minute sessions will be conducted 3-4 times per week for a total of 48 sessions over 12 to 16 weeks.; Other Names: Lokomat; Other: Harness-supported multimodal balance training; 30-minute sessions will be conducted 3-4 times per week for a total of 48 sessions over 12 to 16 weeks.; Other Names: balance exercises, skilled hand exercises
Active Comparator: Treadmill then Multimodal training; Robotic body weight supported treadmill training will be applied using the Lokomat apparatus. Following a washout period of at least 6 weeks, Participants will undergo harness-supported balance training exercises while simultaneously performing skilled hand exercises.	Device: Robotic body weight supported treadmill training; 30-minute sessions will be conducted 3-4 times per week for a total of 48 sessions over 12 to 16 weeks.; Other Names: Lokomat; Other: Harness-supported multimodal balance training; 30-minute sessions will be conducted 3-4 times per week for a total of 48 sessions over 12 to 16 weeks.; Other Names: balance exercises, skilled hand exercises

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Motor Evoked Potential (MEP) Amplitude in the Tibialis Anterior Muscle at the End of Training.	Change between baseline and Evaluation #2 in motor evoked potential area in the tibialis anterior muscle.	Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in ISNCSCI Lower Extremity Motor Score.	Change between baseline and Evaluation #2 in lower extremity motor score derived from the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). Range of scores 0-50, higher is better.	Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months)
Change From Baseline in Berg Balance Scale Sitting With Back Unsupported Score.	Change between baseline and Evaluation #2 in Berg sitting unsupported subscore. Range 0-4, higher better.	Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months)
Change in Leg Spasticity on Modified Ashworth Scale	Change between baseline and Evaluation #2 in modified Ashworth Scale. 0-4 score, lower is better.	Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months)
Change in Gait Speed on 10-meter Walk Test.	Change between baseline and Evaluation #2 in gait speed during 10-meter walk test.	Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months)
Change From Baseline in Walking Index for Spinal Cord Injury II (WISCI II) Scale.	Change between baseline and Evaluation #2 in WISCI II score. Scores range 0-20, higher is better.	Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months)
Change From Baseline in Total Number of Steps Taken by Both Feet During Seated 10-second Step Test.	Change between baseline and Evaluation #2 in steps taken during 10-second step test.	Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months)
Change in Subjective Pain as Determined by McGill Pain Questionnaire (Short Form).	Change between baseline and Evaluation #2 in McGill Pain Questionnaire (Subjective Domain). Total scale 0-45, lower is better.	Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months)
Change From Baseline in Endpoint Excursion and Directional Control Parameters Achieved During Seated Limits of Stability Testing.	Seated posturography performed using the "Limits of Stability" module of the Smart EquiTest apparatus (Neurocom) while seated. Directional Control measure.	Time Frame: Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months)
Change From Baseline in Soleus H-reflex Facilitation.	Change between baseline and Evaluation #2 in soleus H-reflex facilitation by transcranial magnetic stimulation (TMS). Short-interval 0-20ms.	Time Frame: Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months)
Changes From Baseline in Survey: Spinal Cord Injury - Spasticity Evaluation Tool (SCI-SET)	Change between baseline and Evaluation #2 in SCI-SET score. Range of scores -105 to +105. Higher is better.	Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months)

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Noam Y Harel, MD PhD, James J. Peters Veterans Affairs Medical Center

Publications and helpful links

General Publications

• Harel NY, Asselin PK, Fineberg DB, Pisano TJ, Bauman WA, Spungen AM. Adaptation of computerized posturography to assess seated balance in persons with spinal cord injury. J Spinal Cord Med. 2013 Mar;36(2):127-33. doi: 10.1179/2045772312Y.0000000053.
• Harel NY, Martinez SA, Knezevic S, Asselin PK, Spungen AM. Acute changes in soleus H-reflex facilitation and central motor conduction after targeted physical exercises. J Electromyogr Kinesiol. 2015 Jun;25(3):438-43. doi: 10.1016/j.jelekin.2015.02.009. Epub 2015 Mar 2.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2013
• Primary Completion (Actual): November 30, 2016
• Study Completion (Actual): October 23, 2017

Study Registration Dates

• First Submitted: November 30, 2012
• First Submitted That Met QC Criteria: November 30, 2012
• First Posted (Estimate): December 4, 2012

Study Record Updates

• Last Update Posted (Actual): February 26, 2018
• Last Update Submitted That Met QC Criteria: January 26, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: spinal cord injuries; electromyography; exercise therapy; postural balance; paraplegia; locomotor activity; transcranial magnetic stimulation, single pulse
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Trauma, Nervous System; Spinal Cord Diseases; Paralysis; Paresis; Wounds and Injuries; Spinal Cord Injuries; Paraparesis; Paraplegia
• Other Study ID Numbers: B0881-W; 5IK2RX000881-03 (U.S. NIH Grant/Contract); 01407 (Other Identifier: Bronx VA Medical Center); SPU-11-077 (Other Identifier: Bronx VA Medical Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: A Limited Dataset (LDS) will be shared in electronic format pursuant to a VA-approved Data Use Agreement. Individually Identifiable Data will be shared pursuant to valid HIPAA Authorization, Informed Consent, and an appropriate written agreement limiting use of the data to the conditions as described in the authorization and consent, and a written assurance from the recipient that the information will be maintained in accordance with the security requirements of 38 CFR Part 1.466.

Drug and device information, study documents

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