Clinical trial NCT03815721: Carry-over Effects of Repetitively Applied Transcutaneous Spinal Cord Stimulation on Spasticity
Official title: Carry-over Effects of Repetitively Applied Transcutaneous Spinal Cord Stimulation on Spasticity and Residual Motor Control in Incomplete Spinal Cord Injured Individuals
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Spinal Cord Injuries
Spasticity, Muscle
Lead sponsor: Swiss Paraplegic Research, Nottwil
Sponsor class: NETWORK
Collaborators: name: Medical University of Vienna
First posted: 2019-01-24
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Spinal cord injury is a devastating condition, causing substantial impairment of vital body functions caudal to the lesion. A major cause of disability stems from spasticity, a common secondary sequelae. Its various clinical manifestations include spasms, clonus, and resistance to passive movements, and often present a major hindrance in rehabilitation, further deteriorate residual motor performance, and negatively impact independence and quality of life. Despite its high prevalence, successful management of spasticity has remained difficult. Standard-of-care treatment modalities are often insufficient or bear the risk of undesirable side effects further accentuating paresis. Epidural stimulation of the lumbar spinal cord via implanted electrodes provides for an alternative approach. It works through modifying the dysregulated neural signal processing of spared spinal circuitry caudal to the injury. Its ameliorative effects on severe lower-limb spasticity have been repetitively reported. Yet, epidural spinal cord stimulation in motor disorders is still off-label, applied in relatively few patients only, also because of its invasive character, the time consuming testing phase for its effective application, and the lack of markers to identify responders in advance. With the development of transcutaneous spinal cord stimulation, a method became available to activate the same input structures to the lumbar spinal cord as with epidural stimulation and hence to induce similar neuromodulatory effects, yet non-invasively, using standard equipment available at rehabilitation centers. A recent proof-of-concept study has shown that a single 30-minute session of transcutaneous spinal cord stimulation controlled various clinical signs of spasticity and augmented residual motor control in spinal cord injured individuals for several hours beyond its application. Further, in one subject, the stimulation was repetitively applied for six weeks, resulting in cumulative therapeutic effects persisting for 10 days after its discontinuation. These observations strongly suggest that the stimulation can induce beneficial neuroplastic adaptations of spared spinal systems and their interaction with residual supraspinal control. The proposed research aims at studying the reproducibility of these findings in a statistically sound cohort of individuals with spinal cord injury and testing the applicability and acceptance of transcutaneous spinal cord stimulation as a home-based therapy.


Eligibility criteria: Inclusion Criteria:

* motor and sensory incomplete spinal cord injury classified as grade C or D on the American Spinal Injury Association Impairment Scale
* neurological level of spinal cord injury: third cervical to tenth thoracic segment
* chronic condition (≥ 12 months post-spinal cord injury)
* preserved segmental and cutaneo-muscular reflexes in the lower limbs
* able to be verticalized for 6 minutes (with walking aids)
* preserved joint mobility, no musculoskeletal diseases
* spasticity (with/without antispasticity medication)
* stable antispasmodic medication one month prior to as well as during study participation

Exclusion Criteria:

* neuromuscular diseases, e.g., amyotrophic lateral sclerosis (ALS), Parkinson's disease, Guillain-Barré syndrome, muscular dystrophy
* dermatological issues at the stimulation site
* acute urinary tract infection at study entry
* active implants (e.g., cardiac pacemaker, drug pump)
* passive implants between the ninth thoracic level and the first lumbal level (e.g. metal screws/plates for surgical stabilization of spinal fractures)
* malignant diseases
* heart insufficiency
* potential pregnancy (pregnancy test to be conducted as part of the first evaluation)

Primary outcomes:
measure: Change in spasticity index
timeFrame: from day 1 to day 57
Secondary outcomes:
measure: Change in numeric rating scale spasticity
timeFrame: day 1, 8, 29, 50 and 57
measure: Change in Modified Ashworth Scale
timeFrame: from day 1 to day 57
measure: Change in adductor tone rating
timeFrame: from day 1 to day 57
measure: Change in Penn Spasm Frequency Scale
timeFrame: from day 1 to day 57
measure: Change in resistance of the lower limbs
timeFrame: from day 1 to day 57
measure: Change in 6-minute walk test
timeFrame: from day 1 to day 57
measure: Change in Walking Index for Spinal Cord Injury II Scale
timeFrame: from day 1 to day 57
Other outcomes:
Locations:
city: Nottwil
country: Switzerland
facility: Swiss Paraplegic Centre
state: LU
Study officials:
affiliation: Medical University Vienna
name: Ursula Hofstötter
role: PRINCIPAL_INVESTIGATOR
affiliation: Swiss Paraplegic Centre
name: Angela Frotzler
role: PRINCIPAL_INVESTIGATOR
References: