NCT05457205

Brief Summary

Spasticity develops months after spinal cord injury (SCI) and persists over time. It presents as a mixture of tonic features, namely increased muscle tone (hypertonia) and phasic features, such as hyperactive reflexes (hyperreflexia), clonus, and involuntary muscle contractions (spasms). Spasticity is often disabling because it interferes with hygiene, transfers, and locomotion and can disturb sleep and cause pain. For these reasons, most individuals seek treatments for spasticity after SCI. New developments in electrical neuromodulation with transcutaneous spinal stimulation (TSS) show promising results in managing spasticity non-pharmacologically. The underlying principle of TSS interventions is that the afferent input generated by posterior root stimulation modifies the excitability of the lumbosacral network to suppress pathophysiologic spinal motor output contributing to distinctive features of spasticity. However, the previous TSS studies used almost identical protocols in terms of stimulation frequency and intensity despite the great flexibility offered by this treatment strategy and the favorable results with the epidural stimulation at higher frequencies. Therefore, the proposed study takes a new direction to systematically investigate the standalone and comparative efficacy of four TSS interventions, including those used in previous studies. Our central hypothesis is that electrical neuromodulation with the selected TSS protocols (frequency: 50/100 Hz; intensity: 0.45 or 0.9 times the sub-motor threshold) can reduce and distinctly modify tonic and phasic components of spasticity on short- and long-term basis. We will test our hypothesis using a prospective, experimental, cross-over, assessor-masked study design in 12 individuals with chronic SCI (more than 1-year post-injury). Aim 1. Determine the time course of changes and immediate after-effects of each TSS protocol on tonic and phasic spasticity. The results will reveal the evolution of changes in spasticity during 30-min of TSS and the most effective protocol for producing immediate aftereffects. Aim 2. Determine the effect of TSS on spasticity after a trial of home-based therapy with each protocol. The participants will administer 30 min of TSS daily for six days with each of the four TSS protocols selected randomly. This aim will reveal the long-term carry-over effects of TSS intervention on various components of spasticity after SCI. Aim 3. Determine the participants' experience with TSS as a home-based therapy through focus group meetings. We will conduct focus group meetings after participants finish the home-based therapy trial. Accomplishing this specific aim will provide a valuable perspective on the value, challenges, and acceptability of TSS as a home-based intervention. The study addresses important questions for advancing scientific knowledge and clinical management of spasticity after SCI. Specifically, it will examine the efficacy of TSS frequencies and intensities on tonic and phasic spasticity. The study results will be relevant for a high proportion of individuals living with SCI that could benefit from this novel and low-cost non-pharmacological approach to managing spasticity after SCI.

Trial Health

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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
12

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Aug 2022

Typical duration for not_applicable

Geographic Reach
1 country

2 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 5, 2022

Completed
8 days until next milestone

First Posted

Study publicly available on registry

July 13, 2022

Completed
1 month until next milestone

Study Start

First participant enrolled

August 16, 2022

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 28, 2025

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

April 5, 2025

Completed
Last Updated

April 12, 2024

Status Verified

April 1, 2024

Enrollment Period

2.5 years

First QC Date

July 5, 2022

Last Update Submit

April 11, 2024

Conditions

Keywords

Transcutaneous Spinal Cord StimulationNeuromodulationElectrical StimulationSpasticityLower Extremities

Outcome Measures

Primary Outcomes (6)

  • Change in posterior root reflex amplitude

    The amplitudes of the posterior root reflexes will be calculated and normalized to the maximum response amplitude from the recruitment curve for each muscle separately. The respective values will be averaged over all muscles and used as an outcome measure.

    Before and after an intervention session (30 minutes)

  • Change in posterior root reflex amplitude (during intervention)

    The amplitudes of the posterior root reflexes will be calculated and normalized to the maximum response amplitude from the recruitment curve for each muscle separately. The respective values will be averaged over all muscles and used as an outcome measure.

    Before and during an intervention session (15 minutes)

  • Change in flexion withdrawal reflex root-mean-square

    The cumulative root-mean-square values of the reflex amplitude in a window from 50 to 200 ms after the stimulation pulse over all recorded muscles.

    Before and after an intervention session (30 minutes)

  • Change in flexion withdrawal reflex root-mean-square (during intervention)

    The cumulative root-mean-square values of the reflex amplitude in a window from 50 to 200 ms after the stimulation pulse over all recorded muscles.

    Before and during an intervention session (15 minutes)

  • Change in pendulum test index

    The pendulum test provides the spasticity index which is calculated based on the knee angle of the initial horizontal leg position of the pendulum test, the angle at which the leg reversed for the first time from flexion to extension, and the final knee resting angle.

    Before and after an intervention session (30 minutes)

  • Change in pendulum test index (during intervention)

    The pendulum test provides the spasticity index which is calculated based on the knee angle of the initial horizontal leg position of the pendulum test, the angle at which the leg reversed for the first time from flexion to extension, and the final knee resting angle.

    Before and during an intervention session (15 minutes)

Secondary Outcomes (6)

  • Change in Modified Ashworth Scale

    Before and after an intervention session (30 minutes)

  • Change in Modified Ashworth Scale (after one week)

    Before and after one week

  • Change in Spinal Cord Assessment Tool for Spastic Reflexes

    Before and after an intervention session (30 minutes)

  • Change in Spinal Cord Assessment Tool for Spastic Reflexes (after one week)

    Before and after one week

  • Change in Penn Spasm Frequency Scale

    Before and after an intervention session (30 minutes)

  • +1 more secondary outcomes

Study Arms (4)

Neuromodulation with 50 Hz and low intensity

EXPERIMENTAL

Transcutaneous spinal stimulation for 30 min with a stimulation frequency of 50 Hz and stimulation intensity of 0.45 x lowest motor threshold (reflex threshold in leg muscles).

Other: Electrical neuromodulation

Neuromodulation with 50 Hz and high intensity

EXPERIMENTAL

Transcutaneous spinal stimulation for 30 min with a stimulation frequency of 50 Hz and stimulation intensity of 0.90 x lowest motor threshold (reflex threshold in leg muscles).

Other: Electrical neuromodulation

Neuromodulation with 100 Hz and low intensity

EXPERIMENTAL

Transcutaneous spinal stimulation for 30 min with a stimulation frequency of 100 Hz and stimulation intensity of 0.45 x lowest motor threshold (reflex threshold in leg muscles).

Other: Electrical neuromodulation

Neuromodulation with 100 Hz and high intensity

EXPERIMENTAL

Transcutaneous spinal stimulation for 30 min with a stimulation frequency of 100 Hz and stimulation intensity of 0.90 x lowest motor threshold (reflex threshold in leg muscles).

Other: Electrical neuromodulation

Interventions

Electrical neuromodulation intervention using transcutaneous spinal stimulation: two self-adhesive semicircle electrodes (forming a 5cm round electrode) will be centered midline over the T11-12 spinal processes, and two 8×13 cm electrodes will be placed paraumbilical and interconnected to serve as a counter electrode. A current-controlled stimulator will deliver symmetric biphasic pulses (500-μs/phase). Electrical stimulation will be applied according to the description in each study arm.

Also known as: Transcutaneous spinal stimulation, Transcutaneous spinal cord stimulation
Neuromodulation with 100 Hz and high intensityNeuromodulation with 100 Hz and low intensityNeuromodulation with 50 Hz and high intensityNeuromodulation with 50 Hz and low intensity

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age 18 years or older
  • History of SCI (ASIA Impairment Scale grades A-D)
  • Time since injury longer than 6 months
  • The presence of at least mild spasticity (\>3) in the lower limbs by self-report of the Numerical Rating Scale (from 0 to 10) of spasticity severity
  • Signed consent form

You may not qualify if:

  • Neurological level of SCI below T11
  • Suspected progression of SCI (e.g., syringomyelia)
  • Ventilatory-dependent
  • Implanted active devices (e.g., intrathecal baclofen pumps)
  • Passive implants (plates, screws) between T10 and L3 vertebras
  • Skin conditions precluding placement of electrodes
  • Ongoing infections
  • Pregnancy
  • Difficulty following instructions
  • No access to a caregiver/family member to help with electrode placement at home
  • Other medical risks/contraindications as determined by the study physicians

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Methodist Rehabilitation Center

Jackson, Mississippi, 39216, United States

RECRUITING

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

RECRUITING

Related Links

MeSH Terms

Conditions

Spinal Cord InjuriesMuscle Spasticity

Interventions

Transcutaneous Electric Nerve Stimulation

Condition Hierarchy (Ancestors)

Spinal Cord DiseasesCentral Nervous System DiseasesNervous System DiseasesTrauma, Nervous SystemWounds and InjuriesMuscular DiseasesMusculoskeletal DiseasesMuscle HypertoniaNeuromuscular ManifestationsNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Electric Stimulation TherapyTherapeuticsPhysical Therapy ModalitiesRehabilitationAnalgesiaAnesthesia and Analgesia

Study Officials

  • Matthias J Krenn, PhD

    University of Mississippi Medical Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthias J Krenn, PhD

CONTACT

Dobrivoje S Stokic, MD, DSc

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor

Study Record Dates

First Submitted

July 5, 2022

First Posted

July 13, 2022

Study Start

August 16, 2022

Primary Completion

February 28, 2025

Study Completion

April 5, 2025

Last Updated

April 12, 2024

Record last verified: 2024-04

Data Sharing

IPD Sharing
Will not share

Locations