Impact of Direct Current Electrical Stimulation on Spasticity Levels and Functional Muscle Use in MS

Multiple Sclerosis Clinical Trial

Official title:

A Pilot Study of Neubie, a Direct Current Electrical Stimulation Device, to Inhibit Lower Extremity Spasticity Levels and Normalize Muscle Functional Use During Transfers and Ambulation in Individuals With Multiple Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04942938
• Other study ID #: 1643900-2
• Status: Completed
• Phase: N/A
• Start date: June 20, 2021
• Est. completion date: July 5, 2022

Study information

• Verified date: August 2022
• Source: Centura Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In an individual with MS the central nervous system (CNS) is over-protective and causes the threshold for stretch reflex and muscle tightness to be set lower than normal. This inhibits normal movement and causes abnormalities in posture, stiffness and at times joint contractures. In this pilot study we hope to assess the ability for the direct current of Neubie, which creates mechanoreceptor inputs and lengthening at the sarcomere level of muscle and joints in the spine and lower extremity, to alter the proprioceptive peripheral nervous system (PNS) at muscle spindle and GTO level with a change in CNS over-guarding during the treatment and after the treatment. If the investigators are able to create normalized stretch and muscle tension at the PNS level, it may be possible to create temporary or sustained CNS level changes. This would allow the amount of stretch and tension at the PNS level to be normalized and possibly reduce spasticity. If this theory is accurate, the investigators may be able to increase access to normalized movement, strength and functional ability in individuals with neuro-compromise.

Description:

Approximately 66%6 to 84% of individuals with multiple sclerosis experience various levels of debilitating spasticity limiting freedom of movement at ankles, knees and hips causing deficits in ambulation, weakness from disuse of muscles not accessible due to spasticity. Per the North American Research Committee on Multiple Sclerosis, a survey was conducted on spasticity prevalence and results show 84% have some degree of spasticity from mild to incapacitating. Spasticity pathophysiology is complex and not completely understood with higher levels of incapacitating spasticity reported in this survey by those who were male, disabled and unemployed, indicating that psychosocial and subjective variables are significant. The pathophysiology currently best understood demonstrates an imbalance between inhibitory dorsal reticulospinal tract (RST) fibers and excitatory bulbopontine tegmentum. RST neurons receive direct somatic, vestibular, tectal, cerebellar and motor excitatory input and are scattered in the ventral and lateral spinal cord columns intermingled with propriospinal fibers. The peripheral Golgi tendon organ of muscle tendon and muscle spindle intrafusal fibers ubiquitous throughout the musculoskeletal system have direct monosynaptic connection to these central nervous system propriospinal fibers and heavily influence the degree of spasticity and overactive stretch reflexes.

Those who deal with all levels of spasticity use compensatory movement strategies causing altered arthrokinematics and have loss of strength, balance and efficient muscle use with postural changes. Spasticity management has been studied and treated from a pharmaceutical standpoint with some improvements but often side effects including fatigue, muscle weakness and cognition limit dosing in oral Baclofen, Dantrolene Sodium, Tizanidine and Benzodiazepines. Marijuana especially in form of cannabinoids shows mixed evidence for spasticity improvement and is a growing area of interest. There is a growing CBD interest in the MS population due to known reduction of CNS neurodegeneration in animal MS studies and no significant negative side effects with possible mild to moderate improvement in spasticity levels. Therapy interventions offered include frequent stretching especially of muscles that cross two joints including lumbricals, hamstrings, gastrocnemius and iliopsoas; light stroking over lower limbs demonstrated a 30% decrease in H-reflex amplitude lasting even 30 minutes after treatment; muscle cooling was shown to reduce muscle stretch activity and clonus; Armutlu et al. Reported significant reduction in plantar flexor spasticity in 10 patients with MS using high-frequency (100Hz) TENS for 20min daily for 4 weeks. Reduction noted on Modified Ashworth Scale (MAS), electrophysiologic measurements and the AI; and serial casting performed over a 9-day period with cast changes every 3 days demonstrated reduced spasticity levels.

The NeuFit company offers a Neubie EMS product with a direct current using high fidelity audio equipment to decrease intensity of the treatment noxious stimulus and protect skin integrity from burns or intolerable pain. This system uses an exponential wave pattern to mimic the natural pattern neurologically to lengthen fibers of the sarcomere and engage force velocity of muscle with minimized protective co-contraction of nearby muscle groups9. The golgi tendon and muscle spindles code for joint position and muscle/tendon stretch with 66% of fibers being intrafusal. Impacting these structures has direct impact on reticulospinal tract (RST) fibers and proprioceptive central fibers modulation of levels of spasticity. However, finding effective means to impact these areas is difficult. The Neubie direct current is designed to improve positioning of these stretch receptors. As discussed within the paper hypothesis, the theory is that this may improve spasticity levels as well as agonist strength enough to create long term, significant functional improvement.

Dr. Terry Wahls who has MS and has studied and marketed a protocol for MS treatment, promotes this product and has a home unit she uses daily to control her own MS symptoms and gain strength. Currently there is no research study conducted on the effects of the Neubie direct current treatment combined with exercise and ramifications of spasticity in multiple sclerosis. There have been only a few studies conducted with quantitative spasticity measures mostly with FES and NMES targeting tibialis anterior and quadriceps to lessen plantar flexor spasticity in spinal cord injury (SCI) and hemiplegia. In the SCI study Mirbagheri et al. observed decreases in intrinsic and reflex dynamic stiffness in all 4 subjects studied over a 16-month period. Robinson et al. stimulated quadriceps muscle pulse duration 500, 20 Hz and amplitude of 100 with spasticity quantitatively reduced immediately after stimulation but return of baseline spasticity level when measured 24 hours later. Levin and Hui-Chan assessed sensory level stimulation of the common peroneal nerve for a total of 15, 60 min sessions for 3 weeks in people with hemiplegia using pulse duration 125 continuously at 99Hz and observed inhibition of H-reflex at soleus, increase in dorsiflexion voluntary force and reductions in stretch reflex at triceps surae. The NeuFit method of treatment allows the recipient to voluntarily concentrically or eccentrically activate muscles while receiving the direct current passive eccentric input. In order to assess the feasibility of this papers' hypothesis the investigators will perform a pilot study of 4-6 individuals with MS in the greater Denver metro area.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: July 5, 2022
• Est. primary completion date: July 5, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Greater than 18 years old (no upper age limit)

2. Physician diagnosed MS (As stated in Rooney S, et al. Disabil Rehabil. 2019, stage of MS did not impact individuals from making neuromuscular or functional gains. All stages of MS will be eligible)

3. Physician clearance to participate

4. Unable to ambulate more than 70 feet at a time and unable to ambulate outside the home, with use of manual chair or power chair as mobility source >= 50% of the time.

5. BLE MMT in hips, knees and ankles <=3/5

6. Modified Ashworth assessed spasticity levels 1-4

Exclusion Criteria:

1. Co-morbidities in cardiovascular disease (myocardial infarction in past 1-year, unstable angina, CHF, h/o arrythmia, h/o CVA or TIA in past year, uncontrolled hypertension)

2. History of epileptic seizures

3. Lower Motor Neuron disease

4. Existing pacemaker, defibrillator or other implanted device (other than baclofen pump)

5. Unstable long bone fractures of lower limb or trunk

6. Allergies to surface electrodes or conductive gel

7. Pregnancy or actively seeking to become pregnant

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Device:
• Neubie
The Neubie is a direct current neuromuscular electrical stimulation device. This system uses an exponential wave pattern to mimic the natural pattern neurologically to lengthen fibers of the sarcomere and engage force velocity of muscle with minimized protective co-contraction of nearby muscle groups. The golgi tendon and muscle spindles code for joint position and muscle/tendon stretch with 66% of fibers being intrafusal. Impacting these structures has direct impact on reticulospinal tract fibers and proprioceptive central fibers modulation of levels of spasticity. The Neubie direct current is designed to improve positioning of these stretch receptors.

Locations

Country	Name	City	State
United States	Centura Health at Home	Littleton	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
Centura Health	NeuFit - Neurological Fitness and Education

Country where clinical trial is conducted

United States, 

References & Publications (6)

Backus D, Burdett B, Hawkins L, Manella C, McCully KK, Sweatman M. Outcomes After Functional Electrical Stimulation Cycle Training in Individuals with Multiple Sclerosis Who Are Nonambulatory. Int J MS Care. 2017 May-Jun;19(3):113-121. doi: 10.7224/1537-2073.2015-036. — View Citation

Etoom M, Khraiwesh Y, Lena F, Hawamdeh M, Hawamdeh Z, Centonze D, Foti C. Effectiveness of Physiotherapy Interventions on Spasticity in People With Multiple Sclerosis: A Systematic Review and Meta-Analysis. Am J Phys Med Rehabil. 2018 Nov;97(11):793-807. doi: 10.1097/PHM.0000000000000970. — View Citation

Meseguer-Henarejos AB, Sánchez-Meca J, López-Pina JA, Carles-Hernández R. Inter- and intra-rater reliability of the Modified Ashworth Scale: a systematic review and meta-analysis. Eur J Phys Rehabil Med. 2018 Aug;54(4):576-590. doi: 10.23736/S1973-9087.17.04796-7. Epub 2017 Sep 13. Review. — View Citation

Mills PB, Dossa F. Transcutaneous Electrical Nerve Stimulation for Management of Limb Spasticity: A Systematic Review. Am J Phys Med Rehabil. 2016 Apr;95(4):309-18. doi: 10.1097/PHM.0000000000000437. Review. — View Citation

Szecsi J, Schlick C, Schiller M, Pöllmann W, Koenig N, Straube A. Functional electrical stimulation-assisted cycling of patients with multiple sclerosis: biomechanical and functional outcome--a pilot study. J Rehabil Med. 2009 Jul;41(8):674-80. doi: 10.2340/16501977-0397. — View Citation

Wahls TL, Reese D, Kaplan D, Darling WG. Rehabilitation with neuromuscular electrical stimulation leads to functional gains in ambulation in patients with secondary progressive and primary progressive multiple sclerosis: a case series report. J Altern Complement Med. 2010 Dec;16(12):1343-9. doi: 10.1089/acm.2010.0080. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Expanded Disability Status Score	The Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability over time. It is widely used in clinical trials and in the assessment of people with MS.The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist.	Baseline, Pre-intervention
Primary	Expanded Disability Status Score	The Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability over time. It is widely used in clinical trials and in the assessment of people with MS.The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist.	6 weeks
Primary	Upper Extremity Reflex Test	Hoffman's sign or reflex is a test that doctors use to examine the reflexes of the upper extremities. This test is a quick, equipment-free way to test for the possible existence of spinal cord compression from a lesion on the spinal cord or another underlying nerve condition.	Baseline, Pre-intervention
Primary	Upper Extremity Reflex Test	Hoffman's sign or reflex is a test that doctors use to examine the reflexes of the upper extremities. This test is a quick, equipment-free way to test for the possible existence of spinal cord compression from a lesion on the spinal cord or another underlying nerve condition.	6 weeks
Primary	12 item MS walking scale	The Multiple Sclerosis Walking Scale is a self-assessment scale which measures the impact of MS on walking. It consists of 12 questions concerning the limitations to walking due to MS. Each item can be answered with 5 options, with 1 meaning no limitation and 5 extreme limitation. A total score can be generated and transformed to a 0 to 100 scale by subtracting the minimum score possible (12) from the patient's score, dividing by the maximum score possible minus the minimum possible (60-12 or 48), and multiplying the result by 100. Walking improvement on the MSWS-12 is indicated by negative change scores.	Baseline, Pre-intervention
Primary	12 item MS walking scale	The Multiple Sclerosis Walking Scale is a self-assessment scale which measures the impact of MS on walking. It consists of 12 questions concerning the limitations to walking due to MS. Each item can be answered with 5 options, with 1 meaning no limitation and 5 extreme limitation. A total score can be generated and transformed to a 0 to 100 scale by subtracting the minimum score possible (12) from the patient's score, dividing by the maximum score possible minus the minimum possible (60-12 or 48), and multiplying the result by 100. Walking improvement on the MSWS-12 is indicated by negative change scores.	3 weeks
Primary	12 item MS walking scale	The Multiple Sclerosis Walking Scale is a self-assessment scale which measures the impact of MS on walking. It consists of 12 questions concerning the limitations to walking due to MS. Each item can be answered with 5 options, with 1 meaning no limitation and 5 extreme limitation. A total score can be generated and transformed to a 0 to 100 scale by subtracting the minimum score possible (12) from the patient's score, dividing by the maximum score possible minus the minimum possible (60-12 or 48), and multiplying the result by 100. Walking improvement on the MSWS-12 is indicated by negative change scores.	6 weeks
Primary	Manual Muscle Test	A standardized set of assessments that measure strength and function.	Baseline, Pre-intervention
Primary	Manual Muscle Test	A standardized set of assessments that measure strength and function.	3 weeks
Primary	Manual Muscle Test	A standardized set of assessments that measure strength and function.	6 weeks
Primary	Muscle Tone Test	The modified Ashworth scale is a clinical tool used to measure the increase of muscle tone. It measures resistance during passive soft-tissue stretching.	Baseline, Pre-intervention
Primary	Muscle Tone Test	The modified Ashworth scale is a clinical tool used to measure the increase of muscle tone. It measures resistance during passive soft-tissue stretching.	3 weeks
Primary	Muscle Tone Test	The modified Ashworth scale is a clinical tool used to measure the increase of muscle tone. It measures resistance during passive soft-tissue stretching.	6 weeks
Primary	Timed 25 Foot Walk Test (T25FW)	The T25FW is a clinical tool that evaluates patients for quantitative mobility and leg function performance test in a timed, 25 foot walk.	Baseline, Pre-intervention
Primary	Timed 25 Foot Walk Test (T25FW)	The T25FW is a clinical tool that evaluates patients for quantitative mobility and leg function performance test in a timed, 25 foot walk.	3 weeks
Primary	Timed 25 Foot Walk Test (T25FW)	The T25FW is a clinical tool that evaluates patients for quantitative mobility and leg function performance test in a timed, 25 foot walk.	6 weeks
Primary	Timed Up and Go (TUG)	The Timed Up and Go test is a simple evaluative test used to measure functional mobility. The test requires the subject to rise from a chair, walk 3.0 m at a comfortable pace to a mark placed on the floor, turn around at the 3.0 m mark, walk back to the starting point, and return to sitting in the chair. The test's score is the time it takes the subject takes to complete the test.	Baseline, Pre-intervention
Primary	Timed Up and Go (TUG)	The Timed Up and Go test is a simple evaluative test used to measure functional mobility. The test requires the subject to rise from a chair, walk 3.0 m at a comfortable pace to a mark placed on the floor, turn around at the 3.0 m mark, walk back to the starting point, and return to sitting in the chair. The test's score is the time it takes the subject takes to complete the test.	3 weeks
Primary	Timed Up and Go (TUG)	The Timed Up and Go test is a simple evaluative test used to measure functional mobility. The test requires the subject to rise from a chair, walk 3.0 m at a comfortable pace to a mark placed on the floor, turn around at the 3.0 m mark, walk back to the starting point, and return to sitting in the chair. The test's score is the time it takes the subject takes to complete the test.	6 weeks
Primary	Multiple Sclerosis Impact Scale (MSIS-29)	The MSIS-29 is a 29-item self-report measure with 20 items associated with a physical scale and 9 items with a psychological scale. Items ask about the impact of MS on day-to-day life in the past two weeks. All items have 5 response options: 1 "not at all" to 5 "extremely".	Baseline, Pre-intervention
Primary	Multiple Sclerosis Impact Scale (MSIS-29)	The MSIS-29 is a 29-item self-report measure with 20 items associated with a physical scale and 9 items with a psychological scale. Items ask about the impact of MS on day-to-day life in the past two weeks. All items have 5 response options: 1 "not at all" to 5 "extremely".	3 weeks
Primary	Multiple Sclerosis Impact Scale (MSIS-29)	The MSIS-29 is a 29-item self-report measure with 20 items associated with a physical scale and 9 items with a psychological scale. Items ask about the impact of MS on day-to-day life in the past two weeks. All items have 5 response options: 1 "not at all" to 5 "extremely".	6 weeks