Neuromodulation to Reduce Muscle Stiffness Following Spinal Cord Injury

March 22, 2024 updated by: Matthias J. Krenn, PhD, University of Mississippi Medical Center

Shared and Distinct Antispastic Effects of Electrical and Pharmacological Neuromodulation

People with spinal cord injuries may experience muscle tightness or uncontrollable spasms. This study is being conducted to investigate whether transcutaneous spinal stimulation can improve these symptoms. Transcutaneous spinal stimulation is a non-surgical intervention by applying electrical currents using skin electrodes over the lower back and belly.

The investigators want to see how well the intervention of transcutaneous spinal stimulation performs by testing different levels of stimulation pulse rates. Also, transcutaneous spinal stimulation is compared to muscle relaxants such as baclofen and tizanidine, commonly given to people with spinal cord injuries, to reduce muscle stiffness and spasms. By doing this, the investigators hope to discover if transcutaneous spinal stimulation similarly reduces muscle spasms and stiffness or if combining both methods works best. This could help improve treatment options for people with spinal cord injuries in the future.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

The primary questions to be addressed are whether the intervention reduces muscle stiffness and spasms and alters spinal reflexes:

  • Using a 100-Hz (a measure of frequency) transcutaneous spinal stimulation is better than using a 50-Hz.
  • Transcutaneous spinal stimulation at 50 Hz differs from a single dose of baclofen.
  • Transcutaneous spinal stimulation at 50 Hz differs from a single dose of tizanidine.
  • Combining the 50 Hz stimulation with either baclofen or tizanidine decreases spasticity more than just taking the medicine alone.

Participants will visit the Methodist Rehabilitation Center in Jackson, Mississippi, six times over a period of 3 to 5 weeks. During the first visit, the overall health and motor and sensory functions will be assessed following a spinal cord injury. For the next five visits, participants will take a study medication (tizanidine, baclofen, or a placebo). After an hour, they will receive a continuous 30-minute transcutaneous spinal stimulation at either 50 Hz, 100 Hz, or sham. The spinal reflexes and clinical assessments will be evaluated before, during, and after each intervention.

Study Type

Interventional

Enrollment (Estimated)

16

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Matthias J Krenn, Ph.D.
  • Phone Number: 601-364-3413
  • Email: mkrenn@umc.edu

Study Contact Backup

Study Locations

  • United States
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
        • Contact:
          • Matthias J Krenn, PhD
          • Phone Number: 601-364-3413
          • Email: mkrenn@umc.edu
      • Jackson, Mississippi, United States, 39216
        • Methodist Rehabilitation Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion criteria:

  • Age 18 years or older
  • History of spinal cord injury
  • Time since diagnosis longer than six months
  • Presence of spasticity in the lower limbs (≥ 3 on the Numerical Rating Scale of Spasticity Severity [range from 0 to 10])
  • If needed, agreement to reduce antispastic medication

Exclusion criteria:

  • Neurological level of spinal cord injury below T11
  • Ventilatory-dependent
  • Change in neurological status over the past 2 months
  • Rigidity, contraction, or passive range of motion of less than 40 deg in both knee joints
  • Botulinum toxin injections in lower extremities in the previous 3 months before enrollment
  • Systolic blood pressure at rest lower than 90 mm Hg
  • Implanted active devices (e.g., intrathecal baclofen pumps)
  • Passive implants (plates, screws) between T11 and L2 vertebras
  • Skin conditions precluding placement of electrodes
  • Pressure ulcers stage 2 or higher on the gluteal area or lower extremities
  • Receiving antibiotics for infections
  • Pregnancy
  • Difficulty following instructions
  • Participation in another study with investigational drugs or devices within the 30 days preceding and during the present study
  • Other medical risks/contraindications as determined by the study physicians

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Transcutaneous spinal stimulation in combination of baclofen/tizanidine/placebo

Each participant will receive five distinct interventions:

  • Transcutaneous spinal stimulation at 100 Hz for 30 minutes with a placebo
  • Transcutaneous spinal stimulation at 50 Hz for 30 minutes with a placebo
  • Transcutaneous spinal stimulation at 50 Hz for 30 minutes with a single-dose baclofen
  • Transcutaneous spinal stimulation at 50 Hz for 30 minutes with a single-dose tizanidine
  • Transcutaneous spinal stimulation (sham) for 30 minutes with a placebo
Device: Transcutaneous spinal stimulation at 100 Hz
Transcutaneous spinal stimulation (TSS) is a non-invasive neuromodulation method that uses electrical currents to stimulate sensory fibers. The procedure involves placing surface electrodes midline on the lower back (T11-12 spinal processes) and on each side of the belly button. The stimulation frequency during the intervention is 100 Hz, performed at a sub-motor threshold for 30 minutes.
Device: Transcutaneous spinal stimulation at 50 Hz
Transcutaneous spinal stimulation (TSS) is a non-invasive neuromodulation method that uses electrical currents to stimulate sensory fibers. The procedure involves placing surface electrodes midline on the lower back (T11-12 spinal processes) and on each side of the belly button. The stimulation frequency during the intervention is 50 Hz, performed at a sub-motor threshold for 30 minutes.
Combination product: Transcutaneous spinal stimulation at 50 Hz and single dose of baclofen

Transcutaneous spinal stimulation (TSS) is a non-invasive neuromodulation method that uses electrical currents to stimulate sensory fibers. The procedure involves placing surface electrodes midline on the lower back (T11-12 spinal processes) and on each side of the belly button. The stimulation frequency during the intervention is 50 Hz, performed at a sub-motor threshold for 30 minutes.

Study participants will receive a single dose of baclofen, a centrally-acting muscle relaxant belonging to the class of gamma-aminobutyric acid (GABA) analogs. Its primary mechanism involves acting on the GABA receptors in the brain and spinal cord to decrease spasticity. Participants will receive baclofen orally at a single dose of 10 mg.

Combination product: Transcutaneous spinal stimulation at 50 Hz and single dose of tizanidine

Transcutaneous spinal stimulation (TSS) is a non-invasive neuromodulation method that uses electrical currents to stimulate sensory fibers. The procedure involves placing surface electrodes midline on the lower back (T11-12 spinal processes) and on each side of the belly button. The stimulation frequency during the intervention is 50 Hz, performed at a sub-motor threshold for 30 minutes.

Study participants will receive a medication called tizanidine, which is an alpha-2 adrenergic agonist. This medication works by inhibiting presynaptic motor neurons, resulting in a reduction of muscle spasticity. It is commonly used to manage spasticity caused by neurological disorders. Each participant will be given a single oral dose of 4 mg of tizanidine as part of this trial.

Device: Sham transcutaneous spinal stimulation
Sham Transcutaneous spinal stimulation (TSS) involves placing two surface electrodes midline on the lower back (T11-12 spinal processes). The stimulation frequency during the intervention is 50 Hz, performed for 30 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline of posterior root reflexes (PRRs) recruitment curves.
Time Frame: Baseline and at post-intervention (100 minutes)
Change in area under the recruitment curve of PRRs after the intervention compared to the baseline. These reflexes are elicited by transcutaneous spinal stimulation and recorded in key muscles of the lower extremities.
Baseline and at post-intervention (100 minutes)
Change from baseline of flexion withdrawal reflex (FWR) response amplitude.
Time Frame: Baseline and at post-intervention (100 minutes)
Change in the amplitude of the FWR response after the intervention compared to the baseline. The reflex response indicates neural circuitry function and spasticity in individuals with neurological conditions. It is measured by eliciting a motor response through a standardized electrical stimulus and quantifying the change in muscle activity.
Baseline and at post-intervention (100 minutes)
Change from baseline of stretch reflex (SR) response amplitude.
Time Frame: Baseline and at post-intervention (100 minutes)
Change in the amplitude of the SR response after the intervention compared to the baseline. The reflex response indicates spasticity and muscle tone in participants with neurological disorders. The amplitude of the reflex response reflects the muscle's reaction to stretch.
Baseline and at post-intervention (100 minutes)
Change from baseline in muscle stiffness as measured by the Modified Ashworth Scale (MAS),
Time Frame: Baseline and at post-intervention (100 minutes)
Change in cumulative scores of Modified Ashworth Scale in bilaterally five lower extremity muscles (score range: 0 to 40, where higher scores denote worsening outcomes) before and after the 30-minute intervention. The Modified Ashworth Scale is a clinically validated tool that measures resistance during passive soft-tissue stretching and indicates spasticity.
Baseline and at post-intervention (100 minutes)
Change from baseline in spasms as measured by the Spinal Cord Assessment Tool for Spastic Reflexes (SCATS).
Time Frame: Baseline and at post-intervention (100 minutes)
Change in the cumulative score of the Spinal Cord Assessment Tool for Spastic Reflexes, encompassing clonus, flexor spasms, and extensor spasms bilaterally, with a scoring range from 0 to 18, where higher scores denote worsening outcomes. The Spinal Cord Assessment Tool for Spastic Reflexes is a clinical tool designed to evaluate spastic reflexes in individuals with spinal cord injury specifically. It quantitatively measures the severity and pattern of spasticity by assessing involuntary muscle contractions in response to external stimuli.
Baseline and at post-intervention (100 minutes)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline of posterior root reflexes (PRRs) recruitment curves.
Time Frame: Baseline and at during transcutaneous spinal stimulation (80 minutes)
Change in area under the recruitment curve of PRRs during transcutaneous spinal stimulation compared to the baseline. These reflexes are elicited by transcutaneous spinal stimulation and recorded in key muscles of the lower extremities.
Baseline and at during transcutaneous spinal stimulation (80 minutes)
Change from baseline of flexion withdrawal reflex (FWR) response amplitude.
Time Frame: Baseline and at during transcutaneous spinal stimulation (80 minutes)
Change in the amplitude of the FWR response during transcutaneous spinal stimulation compared to the baseline. The reflex response indicates neural circuitry function and spasticity in individuals with neurological conditions. It is measured by eliciting a motor response through a standardized electrical stimulus and quantifying the change in muscle activity.
Baseline and at during transcutaneous spinal stimulation (80 minutes)
Change from baseline of stretch reflex (SR) response amplitude.
Time Frame: Baseline and at during transcutaneous spinal stimulation (80 minutes)
Change in the amplitude of the SR response during transcutaneous spinal stimulation compared to the baseline. The reflex response indicates spasticity and muscle tone in participants with neurological disorders. The amplitude of the reflex response reflects the muscle's reaction to stretch.
Baseline and at during transcutaneous spinal stimulation (80 minutes)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Mississippi Medical Center

Collaborators

The Craig H. Neilsen Foundation
Methodist Rehabilitation Center

Investigators

  • Principal Investigator: Matthias J Krenn, Ph.D., University of Mississippi Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2024

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

November 17, 2023

First Submitted That Met QC Criteria

February 21, 2024

First Posted (Actual)

February 23, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2024

Last Update Submitted That Met QC Criteria

March 22, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UMMC-IRB-2023-125

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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