Neuromodulation to Reduce Muscle Stiffness Following Spinal Cord Injury

Spinal Cord Injuries Clinical Trial

Official title:

Shared and Distinct Antispastic Effects of Electrical and Pharmacological Neuromodulation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06274021
• Other study ID #: UMMC-IRB-2023-125
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: April 1, 2024
• Est. completion date: December 31, 2025

Study information

• Verified date: March 2024
• Source: University of Mississippi Medical Center
• Contact: Matthias J Krenn, Ph.D.
• Phone: 601-364-3413
• Email: mkrenn[@]umc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 16
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Spinal Cord Injuries
• Spinal Cord Injury
• Spinal Cord Injury Cervical
• Spinal Cord Injury Thoracic
• Wounds and Injuries

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Methodist Rehabilitation Center	Jackson	Mississippi
United States	University of Mississippi Medical Center	Jackson	Mississippi

Sponsors (3)

Lead Sponsor	Collaborator
University of Mississippi Medical Center	Methodist Rehabilitation Center, The Craig H. Neilsen Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline of posterior root reflexes (PRRs) recruitment curves.	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)
Primary	Change from baseline of flexion withdrawal reflex (FWR) response amplitude.	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)
Primary	Change from baseline of stretch reflex (SR) response amplitude.	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)
Primary	Change from baseline in muscle stiffness as measured by the Modified Ashworth Scale (MAS),	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)
Primary	Change from baseline in spasms as measured by the Spinal Cord Assessment Tool for Spastic Reflexes (SCATS).	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	Change from baseline of posterior root reflexes (PRRs) recruitment curves.	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)
Secondary	Change from baseline of flexion withdrawal reflex (FWR) response amplitude.	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)
Secondary	Change from baseline of stretch reflex (SR) response amplitude.	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)