Electrical Neuromodulation for Modifying Spinal Network Involved in Spasticity

NCT07792616 | Active Not Recruiting

• 1 other identifier: UMMC-IRB-2022-197
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief 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

Keywords

Spinal Cord Injury; Spasticity; Transcutaneous spinal stimulation; Transcutaneous spinal cord stimulation; Neuromodulation; Electrical stimulation; Posterior root reflex; Flexion withdrawal reflex; Baclofen; Tizanidine; Lower extremity

Outcome Measures

Primary Outcomes (2)

• Change from baseline in soleus posterior root reflex peak-to-peak amplitude

  The soleus posterior root reflex is evoked by transcutaneous spinal stimulation. Five reflexes are recorded at least 5 seconds apart to avoid homosynaptic suppression. Peak-to-peak amplitude is measured in a window from 15 to 50 milliseconds after the stimulation artifact and averaged over the five repetitions, in millivolts. The outcome is the change in mean posterior root reflex amplitude from the pre-drug baseline, compared between the 30 Hz and 75 Hz stimulation blocks and between stimulation and drug conditions.

  Baseline before drug intake (A0); 60 minutes after drug intake and before stimulation (A1); during the 15-minute stimulation block (A2 and A4); and 5 minutes after each stimulation block ends (A3 and A5).

• Change from baseline in flexion withdrawal reflex amplitude

  The flexion withdrawal reflex is elicited by a train of 11 pulses, delivered through an electrode over the medial arch of the foot, using 1-millisecond monophasic pulses separated by 2 milliseconds, at 1.5 and 3 times the reflex threshold, with three stimuli at least 20 seconds apart to avoid habituation. The root mean square value of electromyographic activity in the tibialis anterior is calculated in a window from 50 to 200 milliseconds after the stimulation artifact. The outcome is the change in the root mean square value from the pre-drug baseline.

  Baseline before drug intake (A0); 60 minutes after drug intake and before stimulation (A1); during the 15-minute stimulation block (A2 and A4); and 5 minutes after each stimulation block ends (A3 and A5).

Secondary Outcomes (4)

• Change from baseline in normalized posterior root reflex amplitude

  Baseline before drug intake (A0); 60 minutes after drug intake and before stimulation (A1); during the 15-minute stimulation block (A2 and A4); and 5 minutes after each stimulation block ends (A3 and A5).

• Change from baseline in Spinal Cord Assessment Tool for Spastic Reflexes sum score

  Baseline before drug intake (A0), 60 minutes after drug intake and before stimulation (A1), and 5 minutes after the second stimulation block ends (A5).

• Change from baseline in Modified Ashworth Scale sum score

  Baseline before drug intake (A0), 60 minutes after drug intake and before stimulation (A1), and 5 minutes after the second stimulation block ends (A5).

• Change from baseline in pendulum test spasticity index

  Baseline before drug intake (A0); 60 minutes after drug intake and before stimulation (A1); during the 15-minute stimulation block (A2 and A4); and 5 minutes after each stimulation block ends (A3 and A5).

Study Arms (1)

Spinal stimulation with tizanidine, baclofen, or placebo

EXPERIMENTAL

All participants receive every study condition in a within-subjects crossover design. Each participant attends one evaluation visit, followed by three data-collection visits spaced about one week apart. At each data collection visit, the participant takes a single oral capsule containing tizanidine 2 mg, baclofen 20 mg, or matched placebo, in an order assigned at random across the three visits. One hour after intake, the participant receives two 15-minute blocks of continuous transcutaneous spinal stimulation, one at 30 Hz and one at 75 Hz, in an order assigned at random within the visit. Stimulation intensity is set individually below the motor threshold determined from posterior root reflex recruitment curves. Neurophysiological and clinical assessments are performed before drug intake, one hour after drug intake, during the middle 5 minutes of each stimulation block, and 5 minutes after the end of each stimulation block.

Other: Transcutaneous spinal stimulation at 30 Hz; Other: Transcutaneous spinal stimulation at 75 Hz; Drug: Tizanidine; Drug: Baclofen; Drug: Placebo

Interventions

Transcutaneous spinal stimulation at 30 Hz OTHER

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.

Spinal stimulation with tizanidine, baclofen, or placebo

Transcutaneous spinal stimulation at 75 Hz OTHER

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.

Spinal stimulation with tizanidine, baclofen, or placebo

Tizanidine DRUG

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.

Spinal stimulation with tizanidine, baclofen, or placebo

Baclofen DRUG

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.

Spinal stimulation with tizanidine, baclofen, or placebo

Placebo DRUG

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.

Spinal stimulation with tizanidine, baclofen, or placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older
• History of spinal cord injury (ASIA Impairment Scale grades A-D)
• Time since injury longer than six months
• The presence of at least mild spasticity (\>3) in the lower limbs, as self-reported on the Numerical Rating Scale of spasticity severity from 0 (no spasticity) to 10 (spasticity as bad as you can imagine)
• Agreement to reduce antispastic medication, if needed

You may not qualify if:

• Neurological level of SCI below T11
• Ventilatory-dependent
• Suspected progression of SCI (e.g., syringomyelia)
• Rigidity, contraction, or passive range of motion of \<40 deg in both knee joint
• Systolic blood pressure at rest \<90 mm Hg
• Implanted active devices (e.g., ITB pumps)
• Passive implants (plates, screws) between T10 and L3 vertebras
• Skin conditions precluding placement of electrodes
• Skin breakdown on their sacrum, ischii or lower extremities
• Ongoing infections
• Pregnancy
• Difficulty following instructions
• Other medical risks/contraindications as determined by the study physicians.

Sponsors & Collaborators

• University of Mississippi Medical Center: lead
• Methodist Rehabilitation Center: collaborator

Study Sites (2)

Methodist Rehabilitation

Jackson, Mississippi, 39216, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

MeSH Terms

Conditions

Spinal Cord Injuries; Muscle Spasticity; Spasm; Muscle Hypertonia

Interventions

tizanidine; Baclofen

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Matthias J. Krenn, Ph.D.

  University of Mississippi Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The participant and the outcomes assessor are unaware of which capsule is administered. Tizanidine, baclofen, and placebo are compounded by the study pharmacist into capsules identical in appearance, and allocation is recorded in a password-protected code file that is safeguarded until data analysis and opened earlier only in the event of a medical emergency or a study audit. Stimulation frequency is not masked from the person operating the stimulator.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Each participant receives every study condition in a within-subjects crossover design. Across three data collection visits spaced about one week apart, participants receive a single oral dose of tizanidine, baclofen, or placebo, one per visit, in a random order. Within each visit, two 15-minute blocks of transcutaneous spinal stimulation at 30 Hz and at 75 Hz are delivered in an order assigned at random. Each participant therefore serves as his or her own control across six drug-by-frequency conditions, thereby reducing outcome variability and limiting the influence of injury and spasticity severity as confounders.

Study Record Dates

• First Submitted: August 25, 2026
• First Posted: August 28, 2026
• Study Start: July 13, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): July 14, 2027
• Last Updated: August 28, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)