Electrical Neuromodulation for Modifying Spinal Network Involved in Spasticity

Summary

Muscle stiffness and muscle spasms are common after spinal cord injury. They can interfere with washing and dressing, moving between the bed and a wheelchair, walking, and sleep, and they can cause pain. Oral medications are the usual first-line treatment, but many people report limited benefit or side effects.

This study examines a non-surgical method called transcutaneous spinal stimulation. Surface electrodes are placed on the lower back and on the abdomen, and an electrical current is passed between them to activate nerve fibers entering the spinal cord.

Adults who have had a spinal cord injury and have muscle stiffness or spasms in the legs may participate. Each participant takes part in all parts of the study and serves as their own comparison. Participants attend four visits at one study site, about one week apart. The first visit is for consent and a clinical examination. At each of the next three visits, the participant receives one capsule containing tizanidine, baclofen, or an inactive substance (placebo), in an order assigned by chance. One hour later, the participant receives two 15-minute periods of spinal stimulation, one at 30 pulses per second and one at 75 pulses per second, also in an order assigned by chance. Neither the participant nor the person conducting the testing knows which capsule was taken.

Leg reflexes, muscle activity, and knee movement are measured before the capsule is taken, one hour after it is taken, during each period of stimulation, and after each period of stimulation. Clinical scales for stiffness and spasms are also scored. The study compares the two stimulation rates, compares stimulation with each medicine given alone, and examines whether adding stimulation to a medicine has a larger effect than stimulation alone.

Conditions

• Spinal Cord Injuries (Complete and Incomplete)
• Spinal Cord Injury
• Spinal Cord Injury Cervical
• Spinal Cord Injury Thoracic
• Spinal Cord Injuries
• Spasticity
• Spasm
• Muscle Spasticity
• Muscle Hypertonia
• Muscle Spasm

Interventions

OTHER

Transcutaneous spinal stimulation at 30 Hz

Transcutaneous spinal stimulation is a non-invasive method that delivers electrical current through surface electrodes to activate afferent fibers in the lumbosacral posterior roots. A self-adhesive electrode array is placed midline over the T11-T12 spinous processes, and a pair of interconnected large electrodes is placed paraumbilically to serve as the counter electrode. Symmetric biphasic pulses of 500 microseconds per phase are delivered by a current-controlled stimulator at a constant intensity set individually below the motor threshold (determined from posterior root reflex recruitment curves) and not exceeding the maximum tolerable intensity. The stimulation frequency is 30 Hz, and the block lasts 15 minutes continuously.

OTHER

Transcutaneous spinal stimulation at 75 Hz

Transcutaneous spinal stimulation is a non-invasive method that delivers electrical current through surface electrodes to activate afferent fibers in the lumbosacral posterior roots. A self-adhesive electrode array is placed midline over the T11-T12 spinous processes, and a pair of interconnected large electrodes is placed paraumbilically to serve as the counter electrode. Symmetric biphasic pulses of 500 microseconds per phase are delivered by a current-controlled stimulator at a constant intensity set individually below the motor threshold (determined from posterior root reflex recruitment curves) and not exceeding the maximum tolerable intensity. The stimulation frequency is 75 Hz, and the block lasts 15 minutes continuously.

DRUG

Tizanidine

Tizanidine is an alpha-2 adrenergic agonist used to reduce spasticity. A generic tablet is crushed by the study pharmacist, mixed with lactose powder, and packed into a capsule identical in appearance to the baclofen and placebo capsules. Participants receive a single oral dose of 2 mg at one of the three data collection visits, and a member of the study team witnesses intake. Assessment is repeated one hour after intake, coinciding with the expected peak plasma concentration.

DRUG

Baclofen

Baclofen is a gamma-aminobutyric acid type B receptor agonist used to reduce spasticity. A generic tablet is crushed by the study pharmacist, mixed with lactose powder, and packed into a capsule identical in appearance to the tizanidine and placebo capsules. Participants receive a single oral dose of 20 mg at one of the three data collection visits, and a member of the study team witnesses intake. Assessment is repeated one hour after intake, coinciding with the expected peak plasma concentration.

DRUG

Placebo

The placebo capsule contains lactose powder only and is identical in appearance to the tizanidine and baclofen capsules. It is prepared by the study pharmacist and given as a single oral dose at one of the three data collection visits, with intake witnessed by a member of the study team. The placebo visit provides the reference condition for the comparison between the two stimulation frequencies.

Sponsors & Collaborators

• Methodist Rehabilitation Center

  collaborator OTHER

• University of Mississippi Medical Center

  lead OTHER

Principal Investigators

• Matthias J. Krenn, Ph.D. · University of Mississippi Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-07-13

Primary Completion

2026-12-31

Completion

2027-07-14

Countries

• United States

Study Locations