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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
12
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.
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.
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.
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.
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.
Methodist Rehabilitation
Jackson, Mississippi, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
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.
Time frame: 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.
Time frame: 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 normalized posterior root reflex amplitude
Posterior root reflex amplitudes in 8 muscles, bilaterally, recorded before and during transcutaneous spinal stimulation are normalized to the maximum response amplitude obtained from that muscle's recruitment curve, then averaged across all recorded muscles. The outcome is the change in the mean normalized amplitude relative to the pre-drug baseline, expressed as a proportion of the muscle-specific maximum response
Time frame: 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
The Spinal Cord Assessment Tool for Spastic Reflexes grades three types of spastic motor behavior: ankle clonus, flexor spasms, and extensor spasms, scored bilaterally. The sum score ranges from 0 to 18, where 0 indicates no appearance of spasticity and higher scores indicate more severe spastic reflex behavior. Testing is performed with the participant supine. The outcome is the change in sum score from the pre-drug baseline.
Time frame: 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
The Modified Ashworth Scale grades resistance to passive movement in the hip adductors, knee extensors, knee flexors, and ankle plantar flexors bilaterally. Individual muscle scores range from 0 to 4, with a grade of 1+ scored as 1.5. The sum score across the 10 tested muscle groups ranges from 0 to 40, where 0 indicates no increase in muscle tone in any tested muscle group and higher scores indicate greater muscle tone. Testing is performed with the participant supine. The outcome is the change in sum score from the pre-drug baseline.
Time frame: 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
The examiner brings the lower leg to maximal extension, releases it, and allows it to swing freely to rest, three times per leg at 30 second intervals, with knee joint angle. The spasticity index is calculated from three angles: the initial horizontal leg position, the angle of first reversal from flexion to extension, and the final resting angle, as (first reversal angle minus start angle) divided by 1.6 times (resting angle minus start angle). Values above 1 denote non-spastic conditions and 0 denotes extreme spasticity. The outcome is the change in the spasticity index from the pre-drug baseline.
Time frame: 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).
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