Neuromodulation to Reduce Muscle Stiffness Following Spinal Cord Injury

NCT ID: NCT06274021

Last Updated: 2024-07-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-01
• Study Completion Date: 2025-12-31

Brief 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.

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.

Conditions

Spinal Cord Injuries; Spinal Cord Injury; Spinal Cord Injury Cervical; Spinal Cord Injury Thoracic

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Transcutaneous spinal stimulation at 100 Hz

Intervention Type: DEVICE

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

Intervention Type: DEVICE

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.

Transcutaneous spinal stimulation at 50 Hz and single dose of baclofen

Intervention Type: COMBINATION_PRODUCT

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

Intervention Type: COMBINATION_PRODUCT

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.

Sham transcutaneous spinal stimulation

Intervention Type: DEVICE

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DEVICE

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.

Intervention Type: 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.

Intervention Type: COMBINATION_PRODUCT

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.

Intervention Type: DEVICE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Methodist Rehabilitation Center

OTHER

Sponsor Role: collaborator

The Craig H. Neilsen Foundation

OTHER

Sponsor Role: collaborator

University of Mississippi Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Matthias J. Krenn, PhD

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Matthias J Krenn, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Mississippi Medical Center

Locations

Methodist Rehabilitation Center

Jackson, Mississippi, United States

Site Status: RECRUITING

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Matthias J Krenn, Ph.D.

Role: CONTACT

mkrenn@umc.edu

601-364-3413

Dobrivoje S Stokic, M.D., D.Sc.

Role: CONTACT

dstokic@mmrcrehab.org

601-364-3314

Facility Contacts

Dobrivoje S Stokic, MD, DSc

Role: primary

dstokic@mmrcrehab.org

601-364-3314

Matthias J Krenn, PhD

Role: primary

mkrenn@umc.edu

601-364-3413

Other Identifiers

UMMC-IRB-2023-125

Identifier Type: -

Identifier Source: org_study_id