EXOPULSE Mollii Suit, Spasticity, Muscular Oxygenation & Multiple Sclerosis (ENNOX 2)

Study Overview
=================
Brief Summary
-----------------
The goal of this clinical trial is to demonstrate the improvement of muscular oxygenation in patients with Multiple Sclerosis and spasticity using Exopulse Molli suit stimulation. The main questions it aims to answer are: to evaluate the short-term impact of EXOPULSE Molli suit on muscular oxygenation in adult MS patients suffering from spasticity. to assess the effects of Exopulse Mollii suit on spasticity, pain, fatigue, quality of life (QoL), walking and risk of fall. Study subjects will participate in: One baseline visit for inclusion in the study during which the patient will undergo the first session (active or sham) along with an evaluation before and after the session One visit after two weeks during which the patient will undergo the second session (active or sham) along with an evaluation before and after the session One visit two weeks after the second stimulation; where the patients will undergo a fifth evaluation and receive the EXOPULSE Molli Suit for the four-week open label phase to use the suit at home for an active stimulation session every other day for four weeks. One visit at the end of the open label phase to perform the sixth and last evaluation and return the EXOPULSE Molli suit. Researchers will compare both Active and Sham groups to demonstrate the improvement of muscular oxygenation in patients with MS and spasticity using Exopulse Molli.

Detailed Description
-----------------
The study is a randomized crossover, sham-controlled, double-blind trial to demonstrate the improvement of tissue oxygenation and frequent MS symptoms following a single session of active versus sham Exopulse Mollii suit separated by 2 weeks. A 2-week washout period should be enough to prevent a potential carry over effect. After this phase (phase 1), a second open label phase (phase 2) will be proposed for patients to understand the effects of Exopulse Mollii suit employed for one month (3 sessions per week) on tissue oxygenation and MS related symptoms.

Official Title
-----------------
The Effects of EXOPULSE Mollii Suit on Spasticity and Muscular Oxygenation in Patients With Multiple Sclerosis.

Conditions
-----------------
Sclerosis, Multiple, MS (Multiple Sclerosis), Spastic, Spasticity, Muscle, Oxygen Consumption

Intervention / Treatment
-----------------
* Device: EXOPULSE Mollii Suit Stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Definite MS diagnosis according to the 2017 McDonald criteria since at least one month. Age between 18 and 75 years. Ability to walk freely or with the need of support (expanded disability status scale score (EDSS) < 7.5). Being free of relapses in the last three months. Having spasticity with a score of at least 1+ on the MAS. Female patients of child-bearing potential must agree to use adequate birth control measures Voluntarily given, fully informed written and signed consent obtained before any study related procedures are conducted Exclusion Criteria: Being included in another research protocol during the study period. Inability to undergo medical monitor for the study purposes due to geographical or social reasons. Having a cardiac stimulator, a ventriculoperitoneal shunt, an intrathecal baclofen pump or other contraindications to using Exopulse Mollii suit. Being pregnant. Having a change in their pharmacological therapy in the last three months. Suffering from other somatic or neuropsychiatric diagnoses (e.g., arrhythmias, uncontrolled epilepsy, diseases causing osteoarticular and muscular pain). Having a body mass index above 35 Kg/m2. In case of the introduction of a medical device other than Exopulse Mollii suit during the study period. Patients under juridical protection. Prisoners.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: EXOPULSE Mollii Suit Stimulation Active.<br>This will be the EXOPULSE Mollii Suit Active Stimulation. Stimulation will go on for 60 minutes while control unit is on for 60 minutes. | Device: EXOPULSE Mollii Suit Stimulation<br>* We designed a randomized crossover, sham-controlled, double-blind trial to demonstrate the improvement of tissue oxygenation and frequent MS symptoms following a single session of active versus sham Exopulse Mollii suit. A 2-week washout period should be enough to prevent a potential carry over effect. After this phase (phase 1), a second open label phase (phase 2) will be proposed for patients to understand the effects of Exopulse Mollii suit employed for one month (3 sessions per week) on tissue oxygenation and MS related symptoms.<br>|
| Sham Comparator: EXOPULSE Mollii Suit Stimulation Sham.<br>This will be the EXOPULSE Mollii Suit Sham Stimulation. Stimulation will go on for 1 minute then it turns off while the control unit will remain on for total of 60 minutes. | Device: EXOPULSE Mollii Suit Stimulation<br>* We designed a randomized crossover, sham-controlled, double-blind trial to demonstrate the improvement of tissue oxygenation and frequent MS symptoms following a single session of active versus sham Exopulse Mollii suit. A 2-week washout period should be enough to prevent a potential carry over effect. After this phase (phase 1), a second open label phase (phase 2) will be proposed for patients to understand the effects of Exopulse Mollii suit employed for one month (3 sessions per week) on tissue oxygenation and MS related symptoms.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscular Oxygenation using Near-infrared spectroscopy (NIRS) Measurements | Muscular Oxygenation will be assessed using the Near-infrared spectroscopy (NIRS) technology using a PortaMon device it will be employed to assess tissue oxygenation parameter (hemoglobin (tHb) in the territory of the spastic muscles before and after each session. | To be assessed at baseline, week 2, week 4 and week 8 | 
| Muscular Oxygenation using Near-infrared spectroscopy (NIRS) Measurements | Muscular Oxygenation will be assessed using the Near-infrared spectroscopy (NIRS) technology using a PortaMon device it will be employed to assess tissue oxygenation parameter oxyhemoglobin (O2Hb) in the territory of the spastic muscles before and after each session. | To be assessed at baseline, week 2, week 4 and week 8 | 
| Muscular Oxygenation using Near-infrared spectroscopy (NIRS) Measurements | Muscular Oxygenation will be assessed using the Near-infrared spectroscopy (NIRS) technology using a PortaMon device it will be employed to assess tissue oxygenation parameter deoxyhemoglobin (HHb) in the territory of the spastic muscles before and after each session. | To be assessed at baseline, week 2, week 4 and week 8 | 
| Muscular Oxygenation using Near-infrared spectroscopy (NIRS) Measurements | Muscular Oxygenation will be assessed using the Near-infrared spectroscopy (NIRS) technology using a PortaMon device it will be employed to assess tissue oxygenation parameter tissue oxygenation index (TOI%)) in the territory of the spastic muscles before and after each session. | To be assessed at baseline, week 2, week 4 and week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numerical Rating Scale for spasticity. | Spasticity will be evaluated using a Numerical Rating Scale (NRS) score from 0 to 10, 0 being no spasticity and 10 being the worst possible spasticity. | This to be assessed at baseline, then at week 2, week 4 and week 8. | 
| Multiple Sclerosis International Quality of Life Questionnaire. | Quality of life will be measured using the 31-item Multiple Sclerosis International Quality of Life Questionnaire (MusiQoL) This questionnaire consists of 31 questions covering 9 domains including: 1- activity of daily living, 2- physical well-being, 3- relationships with friends, 4- symptoms, 5- relationships with family; 6- relationships with health care systems, 7- sentimental and sexual life, 8- coping; and 9- rejection. The questions are answered by ticking or checking the box that describes best of what patients would feel ranging from 0 to 4, 0 being not at all and 4 always or very much. For MusiQoL, the score of each of the nine sub domains is calculated as the average for the set of questions making up the domain. An overall score is then calculated as the average of all the scores for each subdomain. Prior to computing the final overall score, each domain-specific score is linearly transformed to a 0-100 scale with O being the worst quality of life and 100 the best. | Two weeks after the second stimulation and 4 weeks later at the end of phase 2. | 
| Visual Analog Score for pain. | Pain will be measured using a visual analog score from 0 to 10, 0 being no pain, to 10 being the worst possible pain. | This to be assessed at baseline, then at week 2, week 4 and week 8. | 
| Visual Analog Score for fatigue. | Fatigue will be measured using a visual analog score from 0 to 10, 0 being no fatigue, to 10 being the worst possible fatigue. | This to be assessed at baseline, then at week 2, week 4 and week 8. | 
| Fall risk. | Fall risk will be assessed using the Falls Efficacy Scale- International scale. It is a 16-item scale, including a range of functional activities, that assesses the perceived risk of falling, using a score that will range from 1 to 4, 1 being not at all concerned to 4 being very concerned. | Two weeks after the second stimulation and at the end of phase 2. | 
| Walking ability. | Walking ability will be evaluated by the 12-item Multiple Sclerosis Walking Scale (MSWS-12). Each one of the 12 items will be assessed and assigned numbers from 1 to 5, 1 being not at all to 5 being extremely common, and the results will be added to a total of 60, so the higher the score, the better the mobility. | Two weeks after the second stimulation and at the end of phase 2. | 
| Overall Clinical Improvement. | Evaluation of overall Clinical improvement will be done using the 7-point Clinical Global Impression (CGI). Patient will fill a questionnaire that will address their clinical situation as follows: Very much improved. Much improved. Slightly improved. No change. Slightly worse Much worse. Very much worse The score will range from 1-7, 1 being the best clinical outcome and 7 the worst. | This to be assessed at baseline, then at week 2, and week 8. | 
| Blinding Questionnaire. | Evaluation of patient's blinding to the type of stimulation in the crossover trial periods using a dedicated questionnaire. Patients will be asked whether they think they received the sham or active stimulation. No scale will be used for this measure. | This to be assessed at baseline, then at week 2. | 
| Weight | The patient weight will be measured and recorded in kilograms. | Baseline. | 
| Height | The patient height will be measured and recorded in centimeters. | Baseline. | 
| Muscle tone. | Muscle tone will be evaluated by the Modified Ashworth Scale (MAS). Scores will range from 0 to 4, 0 being no increase or normal muscle tone, to 4 being rigidity in flexion or extension of muscles. | Baseline, and through study completion. | 
| Body Mass Index (BMI) | The weight and height will be combined to report BMI in kg/m^2. BMI of 35 kg/m^2 or more will be used as an exclusion criterion for the study. | Baseline. |