Nutrition, Neuromuscular Electrical Stimulation (NMES) and Secondary Progressive Multiple Sclerosis (SPMS)

Study Overview
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Brief Summary
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The study will use a multimodal therapeutic lifestyle intervention consisting of a study diet, stressing more vegetables and fruit, elimination of foods at greatest risk for food allergy, meditation, self massage, progressive exercise and neuromuscular electrical stimulation for rehabilitation of gait and fatigue disability in the setting of secondary and primary progressive multiple sclerosis with gait disability.

Detailed Description
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Restoration of function is very rare in individuals with MS who have experienced gradual worsening in the absence of acute MS symptoms (relapses) and partial or complete recovery of those acute symptoms (remissions). A recent case report of a patient with secondary progressive MS documented a transition from scooter dependence to mild gait disability following the initiation of electrotherapy in the form of neuromuscular electrical stimulation and nutritional interventions aimed increasing the nutrient density and decreasing the risk of food sensitivity and food allergies. Multiple studies of neuromuscular electrical stimulation in athletes, cerebral palsy and stroke patients have demonstrated gains in strength and coordination. Multiple authors have reported that antioxidants, essential amino acids and micronutrient rich diets are neuroprotective. It is likely that the combination of the intensive nutrition and the electrotherapy contributed to the marked gains in improvement. However in the absence of an additional case report the strength of the association remains unknown. The intent of this study is to replicate the interventions from the case report as closely as possible. Our primary objective is to measure how many and how completely subjects implement 1) the nutritional interventions, 2) the home exercise program intervention, and 3) the electrotherapy intervention and if the improve improved nutrition and exercise are associated with improved function. To assess improvements in function will measure 1) the change in nutritional status as reported in food frequency surveys, 24 hr dietary recalls, 2) change in neurocognitive testing and behaviors, 3) change in self-reported function and disability scales, 4) change in gait and 5) change in medications doses or classes for MS related symptoms. Subjects will be followed for three years. After the first year, subjects will not receive intensive support from the study team. The subjects return at months 18, 24 and 36 to assess adherence with study interventions, function and quality of life. Nutrition intake is assessed again at 24 and 36 months. To assess for safety we will assess safety labs (kidney and liver function tests) and changes in weight, and self reported side effects questionnaire.

Official Title
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Nutrition, Neuromuscular Electrical Stimulation (NMES) and Secondary Progressive Multiple Sclerosis (SPMS)

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Other: Progressive exercise
* Device: Neuromuscular electrical stimulation delivered using the electrical therapy device EMPI 300 PV
* Other: Modified paleolithic diet
* Dietary Supplement: Omega 3 fatty acids
* Dietary Supplement: Full Spectrum vitamin
* Dietary Supplement: Essential - hydroxytyrosol
* Dietary Supplement: Maltodextrin fiber supplement
* Dietary Supplement: Mineral boost (magnesium)
* Dietary Supplement: Niacinamide
* Dietary Supplement: Methyl B12
* Dietary Supplement: Taurine
* Dietary Supplement: creatine
* Dietary Supplement: thiamine
* Dietary Supplement: riboflavin
* Dietary Supplement: N acetylcysteine
* Dietary Supplement: alpha lipoic acid
* Dietary Supplement: L acetyl carnitine
* Dietary Supplement: methyl folate
* Dietary Supplement: coenzyme Q
* Behavioral: meditation
* Behavioral: self massage
* Behavioral: learning
* Dietary Supplement: Coconut oil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Secondary or primary progressive multiple sclerosis Some level of gait disability Tolerance for test electrical therapy session Successful completion of two week Run-IN phase completing the daily logs - Demonstrating > 80% compliance with dietary and behavioral interventions Exclusion Criteria: Antiplatelet or blood thinning medication Cognitive disability or psychiatric disorder making compliance with study interventions difficult Implanted electronic medical device Change in medication in the prior three months Active cancer treatment (skin basal cell or squamous cancer is not an exclusion criteria)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combined intervention<br>Combination intervention consisting of the following: structured modified paleolithic diet, Progressive Exercise, Neuromuscular Electrical Stimulation designed to facilitate the adoption of multiple therapeutic lifestyle behaviors associated with superior health outcomes. | Other: Progressive exercise<br>* Progressive strengthening exercises designed to improve core muscles and muscles of ambulation.<br>Device: Neuromuscular electrical stimulation delivered using the electrical therapy device EMPI 300 PV<br>* Neuromuscular electrical stimulation to train core muscles and ambulation muscles. Device is Empi 300 manufactured by DJO Inc.<br>* Other names: NMES, electrical therapy;Other: Modified paleolithic diet<br>* Diet based upon a Paleolithic diet and structured to increase the consumption of greens, sulfur rich vegetables, bright colors, seaweed and omega 3 fatty acid rich foods.<br>* Other names: Wahls Diet, Paleolithic Diet, Gluten-free, Dairy-free.;Dietary Supplement: Omega 3 fatty acids<br>* 4 grams daily by mouth.<br>* Other names: Pinnaclife Omega 3 fatty acids;Dietary Supplement: Full Spectrum vitamin<br>* Two capsules daily.<br>* Other names: Pinnaclife;Dietary Supplement: Essential - hydroxytyrosol<br>* Two capsules twice daily.<br>* Other names: Pinnaclife Essential;Dietary Supplement: Maltodextrin fiber supplement<br>* One scoop daily.<br>* Other names: Pinnaclife Cleanse;Dietary Supplement: Mineral boost (magnesium)<br>* Two capsules daily<br>* Other names: Pinnaclife Mineral Boost.;Dietary Supplement: Niacinamide<br>* 500 mg daily<br>Dietary Supplement: Methyl B12<br>* Methyl B12 1000 mcg daily<br>Dietary Supplement: Taurine<br>* one gram daily<br>Dietary Supplement: creatine<br>* one teaspoon daily<br>Dietary Supplement: thiamine<br>* 100 mg daily<br>Dietary Supplement: riboflavin<br>* 200 mg daily<br>Dietary Supplement: N acetylcysteine<br>* 1 gram daily<br>Dietary Supplement: alpha lipoic acid<br>* 300 mg twice daily<br>Dietary Supplement: L acetyl carnitine<br>* 500 mg twice daily<br>Dietary Supplement: methyl folate<br>* 1000 mcg one pill four times a week<br>Dietary Supplement: coenzyme Q<br>* 100 mg daily<br>Behavioral: meditation<br>* meditation 15 minutes daily<br>Behavioral: self massage<br>* self massage of hands, feet, ears 15 minutes daily<br>Behavioral: learning<br>* completing puzzles or learning 15 minutes daily<br>Dietary Supplement: Coconut oil<br>* If excessive weight loss occurs, the subject will add 1-2 tablespoons of coconut oil daily to smoothies or foods eaten.<br>* Other names: Extra virgin cold press coconut oil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue severity scale | Self reported fatigue severity scale, (agreement with 9 questions describing impact of fatigue on daily activities) | Baseline, 3 M, 6M, 9M,12 M | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 25 foot walk | Average walking speed calculated from 25 foot walk. Distance (feet)walked divided by time in seconds. Step and stride length, step and stride duration. | baseline, 3M, 6M, 9M, 12M, 18M, 24M 36M | 
| Short Form 36 | Self reported function in multiple domains. | baseline, 3M, 6M, 9M, 12M, 18M, 24M, 36 M | 
| Mood scales | Beck depression index, Beck anxiety index | Baseline, 3 M, 6M, 9M, 12M | 
| Cognitive Scales | Cognitive stability index or cognitive stability test, subscales of Dkef, Wtar, Wais III. | baseline, 3 M, 6M, 9M, 12 M | 
| Medical Symptoms Questionnaire | Detailed review of systems which is scored 0 to 4 for each item. | baseline, 1 M, 2M, 3M, 4M, 5M, 6M, 7M, 8M, 9M, 10 M, 11M, 12M, 18M, 24M, 36M | 
| Side effects log | Questions about potential side effects from vitamin, supplements and diet, questions about potential side effects from NMES, and questions about potential side effects from exercise. | Baseline, 1M, 2M, 3M, 4M, 5M, 6M, 7M, 8M, 9M, 10 M, 11M, 12M | 
| MS Function | Self reported disability scales (from North American Research committee on Multiple Sclerosis) | Baseline, 3 M, 6M, 9M, 12M, 18M, 24M, 36M | 
| Multiple Sclerosis Spasticity Scale-88 | 88 Questions about the impact of spasticity on various activities of daily living | Baseline, 3M, 6M,9M and 12M, 18M, 24M, 36M | 
| Daily log | Daily reports of foods consumed, exercises and activities completed. | Baseline, 1M, 2M, 3M, 4M, 5M, 6M, 7M, 8M, 9M, 10 M, 11M, 12M | 
| Vitamin log | Log of vitamins supplement bottles date opened, date emptied, pill size, number of pills in bottle. | Baseline, 1M, 2M, 3M, 4M, 5M, 6M, 7M, 8M, 9M, 10 M, 11M, 12M | 
| Medical examination | Medical examination | Baseline, 12 M | 
| Neurological examination | Neurological examination | Baseline and 12 M | 
| Exposure history form | History of exposures to chemicals. | Baseline | 
| Health questions | health questions about chronic disease states | Baseline | 
| Menses and pregnancy risk | Questions about menses and potential for pregnancy | Baseline, 3M, 6M, 9M, 12M | 
| Medication audit | Medications | Baseline, 12 M | 
| Functional diagnoses | Questions about past medical history | Baseline | 
| Manual motor testing | Manual motor testing of arms, legs and core muscle groups. | Baseline, 3M, 6M, 9M, 12M | 
| Berg Balance | Tests of balance which are progressively more challenging. | baseline, 3M, 6M, 9M, 12M | 
| Modified Ashworth | Test of spasticity by physical examination. | baseline, 3M, 6M, 9M, 12M | 
| Circumference | Circ. of waist, hips, R and+ L calf and R. and L. thigh. | baseline, 3M, 6M, 9M, 12M | 
| Peak flow | Peak expiratory flow rate. | baseline, 3M, 6M, 9M, 12M | 
| Number of falls in prior two months | Self reported number of falls and associated factors contributing to fall and severity of fall related injuries. | Baseline, 3M, 6M, 9M,12M, 18M, 24M, 36M | 
| Dietary compliance | Assessments, self report, Harvard Food Frequency (baseline, 12 month), 24 hour dietary recalls (6M) | Baseline, 6 month and 12 month, 36 month | 
| Blood pressure | blood pressure | baseline, 3M, 6M, 9M, 12M | 
| Waist/ Hip ratio | circumference of waist over the circumference of hip | baseline, 3M, 6M, 9M, 12M | 
| MS quality of life- 54 | Quality of life questionnaires asking about various aspects of daily life. | Baseline and months 3,6,9,12,18,24,and 36 | 
| Blood Biomarkers | Blood biomarkers of inflammation, and nutritional status. | Baseline, 12 months | 
| Change in functional and structural brain Magnetic Resonance Imaging (MRI) measures | Following sequences: T1 weighted - Pre Gadolinium T1 weighted -Post Gadolinium T2 weighted FLAIR functional MRI during cognitive task Resting state functional MRI Diffusion Tensor Imaging | Between 1 and 12 month post intervention | 
| Fatigue severity scale | Self reported fatigue severity scale, (agreement with 9 questions describing impact of fatigue on daily activities) | 18 M, 24 M, 36 M | 
| Get up and go test time | Total time to get up from chair, walk 10 feet and come back and sit down on the chair. Step and stride length, step and stride duration and double support time. | Baseline, 3M, 6M, 9M, 12M, 18M, 24M, 36M | 
| Change in weight and Body mass index (BMI) | weight measured in Kg Body mass index (BMI) | Baseline, 3M, 6M, 9M, 12M, 18M, 24M, 36M | 
| Blood safety biomarkers | Kidney and liver function tests and complete blood count | Baseline, 1M, 3M, 6M, 9M, 12M, 18M, 24M, 36M | 
| 9 hole peg board test | Time to put 9 pegs in holes and take them out. | Baseline, 3M, 6M, 9M,12M, 18M, 24M, 36M | 
| Paced auditory serial addition task (PASAT) | Addition of two consecutive numbers during a series of numbers heard by subject. | Baseline, 3M, 6M,9M,12M, 18M,24M,36M | 
| Veteran specific activity questionnaire | Questions about the maximum physical activity level. | Baseline, 3M, 6M, 9M, 12M, 18M,24M,36M | 
| Form 38- Daily life | Questions about stressful life events. | 12M, 18M, 24M, 36M | 
| Urine toxicology | 24 hours urine collection and measurement of heavy metals. | Baseline and 12 M | 
| Stool microbial profile | DNA probe for bacteria, parasites and yeast DNA. | Baseline and 12M | 
| Harvard food frequency questionnaire and 24 hour food recalls | Questions regarding food intake and frequency of type of food consumed in last one year. Phone interview asking about food consumed in last 24 hours. | Baseline, 12M, 24M and 36M | 
| Bio impedance analysis | Test to analyze body composition. | Baseline, 12M, 24M and 36M | 
| Exercise and electrical stimulation daily log | Record of exercise, use of electrical stimulation on muscles and physical activity. | Daily baseline through 12M, 14 day-logs before/after 18M, 24M and 36M | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Secondary Progressive Multiple Sclerosis, primary progressive multiple sclerosis