Clinical trial NCT02252666: Exploring the Use of Non-invasive Neuromodulation Combined With Exercise in People With Advanced Multiple Sclerosis (MS)
Official title: Exploring the Use of Non-invasive Neuromodulation Combined With Exercise in People With Advanced Multiple Sclerosis (MS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Multiple Sclerosis
Keywords: MS
balance
standing
control
movement
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
First posted: 2014-09-30
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The investigators hypothesis is that electrical stimulation to the tongue that directly stimulates two cranial nerve nuclei (Trigeminal and Facial Nerve Nuclei), will excite neural impulses to the brainstem and cerebellum. The investigators call this cranial nerve non-invasive neuromodulation (CN-NINM). The activation of these structures induces neuroplasticity when combined with specific physical exercises, can reduce symptoms of advanced MS, targeting primarily postural stability (sitting and standing), upper extremity movement, and ability to perform self-transfers.

Detailed description: The intervention will be similar to that used in the investigators previous work with movement disorders, and will be tailored to the address issues unique to individuals with advanced MS.

The study will enroll a total of 6 subjects having advanced MS that present with significant seated and standing balance, posture, or movement control deficits due to MS.

Subjects will complete twice-daily lab training for two weeks (5 days/week). Each lab training (morning and afternoon) includes 1.5 to 2 hours of instruction in balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training.

Activities are performed in 20-minute sessions with concomitant electrical stimulation of the tongue. The intervention is customized according to each subject's particular symptoms and tolerance. If a subject is not able to perform this amount of training, the training will be adapted to a level that is tolerable.

After these 2 weeks, subjects will continue to perform these same intervention activities at home for 4 weeks. They will return to the lab for 1 week of training and testing, then perform home training for 4 weeks. This cycle is repeated for a total of 5 cycles.

After the 6 months have been completed, subjects may choose to participate in an optional second phase of the study. The second phase includes an additional 12 months of participation in which subjects perform the intervention activities at home training and return to the lab on time per month for 2 hours of testing and 2 hours of training.

If successful, this study would indicate that CN-NINM intervention may reduce the symptoms of advanced MS.

Eligibility criteria: Inclusion Criteria:

* Subjects must be age 18 or older.
* Subjects will have a score between 6.5 to 7.5 on the Kurtzke Expanded Disability Status Scale (EDSS). The EDSS is a method of quantifying disability in people with multiple sclerosis.

  * Score of 6.5: needs constant bilateral support to walk 20 meters without resting.
  * Score of 7.0: unable to walk beyond five meters even with aid, and is essentially restricted to a wheelchair; wheels self and transfers alone, and is active in wheelchair about 12 hours a day.
  * Score of 7.5: unable to take more than a few steps and is restricted to wheelchair, and may need aid to transfer; wheels self, but may require a motorized chair for a full day's activities.
* Subjects will have reached a plateau in an MS focused physical rehabilitation program in the 6 months prior to enrollment.

  * Requiring prior physical therapy will ensure that subjects have a core level of function that will allow them to participate in the study.
  * Requiring that subjects have reached a plateau will ensure that subjects' response to the intervention is due to the use of the device and not to the physical exercises alone.
  * Subjects who have participated in a physical rehabilitation program demonstrate that they are willing and able to commit to a rigorous training regimen.
* Subjects will have a maximum score of 20 on the Trunk Impairment Scale (TIS). The TIS assesses static dynamic sitting balance and trunk coordination in a sitting position. A score of 20 or lower indicates that their ability to adequately maintain sitting posture is affected.
* Subjects may have upper extremity involvement.
* Subjects may have additional symptoms of nystagmus, dysarthria, sensory disturbance, pain, and/or bowel and bladder function. As they present, we will use appropriate assessments at baseline and successive study test points.
* Subjects are their own legal guardians, and are able to understand and give informed consent.

Exclusion Criteria:

Subjects will have no major co-morbidities, especially neurological disorders, uncontrolled pain, hypertension or diabetes. All subjects, if on medications, will not have had any major changes in type or dosage in within 3 months of enrollment. Additionally, candidates will be excluded if they:

* have Functional Systems Scores (FSS) 4 or greater for pyramidal, cerebellar, brainstem, and sensory functions; 3 or greater for bowel and bladder function; and 2 or greater for cerebral function;
* are able to walk independently;
* use tobacco products (these activities tend to reduce tactile sensitivity in the oral cavity);
* have any oral abrasions, cuts, cold sores, piercings, tissue inflammation, or have had oral surgery within the previous 3 months;
* have a pacemaker, or are identified as at-risk for cardiovascular events;
* have a history of seizures;
* have a communicable disease;
* have a biomechanical prosthetic;
* are females who are pregnant.

Primary outcomes:
measure: Trunk Impairment Scale (TIS)
timeFrame: Change from Baseline at 2, 6, 11, 16, and 21 weeks
Secondary outcomes:
measure: Static Standing Balance Test
timeFrame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
measure: Impact of Visual Impairment Scale (IVIS)
timeFrame: Change from Baseline at 2, 6, 11, 16, and 21 weeks
measure: Medical Outcomes Study (MOS) Pain Effects Scale (PES)
timeFrame: Change from Baseline at 2, 6, 11, 16, and 21 weeks
measure: Bladder Control Scale (BLCS)
timeFrame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
measure: Bowel Control Scale (BWCS)
timeFrame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
measure: Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
timeFrame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
measure: Walking Distance
timeFrame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
measure: Walking Speed
timeFrame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
measure: 12-item MS Walking Scale (MSWS-12)
timeFrame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
measure: Box & Blocks (B&B) Assessment - Right
timeFrame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
measure: Box & Blocks (B&B) Assessment - Left
timeFrame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
measure: Multiple Sclerosis Impact Scale (MSIS-29) - Physical
timeFrame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
measure: Multiple Sclerosis Impact Scale (MSIS-29) - Psychological
timeFrame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
measure: Modified Fatigue Impact Scale (MFIS)
timeFrame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
measure: Gross Motor Function Measure (GMFM)
timeFrame: Change from Baseline at 6, 11, 16, 21 and 27 weeks
measure: Slump Test
timeFrame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
measure: Modified Rivermead Mobility Index
timeFrame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
Other outcomes:
measure: Video Nystagmography (VNG)
timeFrame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
Locations:
city: Madison
country: United States
facility: TCNL, 455 Science Drive, Suite 165
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Mitchell E Tyler, MS
role: PRINCIPAL_INVESTIGATOR
References: