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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: 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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52246
      • Univeristy of Iowa/ VA Iowa City VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Combined intervention; 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; Progressive strengthening exercises designed to improve core muscles and muscles of ambulation.; Device: Neuromuscular electrical stimulation delivered using the electrical therapy device EMPI 300 PV; Neuromuscular electrical stimulation to train core muscles and ambulation muscles. Device is Empi 300 manufactured by DJO Inc.; Other Names: NMES, electrical therapy; Other: Modified paleolithic diet; 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.; Other Names: Wahls Diet, Paleolithic Diet, Gluten-free, Dairy-free.; Dietary supplement: Omega 3 fatty acids; 4 grams daily by mouth.; Other Names: Pinnaclife Omega 3 fatty acids; Dietary supplement: Full Spectrum vitamin; Two capsules daily.; Other Names: Pinnaclife; Dietary supplement: Essential - hydroxytyrosol; Two capsules twice daily.; Other Names: Pinnaclife Essential; Dietary supplement: Maltodextrin fiber supplement; One scoop daily.; Other Names: Pinnaclife Cleanse; Dietary supplement: Mineral boost (magnesium); Two capsules daily; Other Names: Pinnaclife Mineral Boost.; Dietary supplement: Niacinamide; 500 mg daily; Dietary supplement: Methyl B12; Methyl B12 1000 mcg daily; Dietary supplement: Taurine; one gram daily; Dietary supplement: creatine; one teaspoon daily; Dietary supplement: thiamine; 100 mg daily; Dietary supplement: riboflavin; 200 mg daily; Dietary supplement: N acetylcysteine; 1 gram daily; Dietary supplement: alpha lipoic acid; 300 mg twice daily; Dietary supplement: L acetyl carnitine; 500 mg twice daily; Dietary supplement: methyl folate; 1000 mcg one pill four times a week; Dietary supplement: coenzyme Q; 100 mg daily; Behavioral: meditation; meditation 15 minutes daily; Behavioral: self massage; self massage of hands, feet, ears 15 minutes daily; Behavioral: learning; completing puzzles or learning 15 minutes daily; Dietary supplement: Coconut oil; If excessive weight loss occurs, the subject will add 1-2 tablespoons of coconut oil daily to smoothies or foods eaten.; Other Names: Extra virgin cold press coconut oil

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Iowa
• Collaborators: DJO Incorporated; Direct MS Canada; Pinnaclife Inc.; TZ Press, LLC

Publications and helpful links

General Publications

• 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.
• Reese D, Shivapour ET, Wahls TL, Dudley-Javoroski SD, Shields R. Neuromuscular electrical stimulation and dietary interventions to reduce oxidative stress in a secondary progressive multiple sclerosis patient leads to marked gains in function: a case report. Cases J. 2009 Aug 10;2:7601. doi: 10.4076/1757-1626-2-7601.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: May 26, 2011
• First Submitted That Met QC Criteria: June 24, 2011
• First Posted (Estimate): June 27, 2011

Study Record Updates

• Last Update Posted (Actual): June 26, 2018
• Last Update Submitted That Met QC Criteria: June 22, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Secondary Progressive Multiple Sclerosis, primary progressive multiple sclerosis
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Anti-Infective Agents; Antiviral Agents; Platelet Aggregation Inhibitors; Antimetabolites; Protective Agents; Photosensitizing Agents; Dermatologic Agents; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Respiratory System Agents; Vitamins; Antioxidants; Antidotes; Vitamin B Complex; Free Radical Scavengers; Nootropic Agents; Expectorants; Acetylcysteine; N-monoacetylcystine; Acetylcarnitine; Nicotinic Acids; Riboflavin; Thioctic Acid; Niacinamide; Niacin; Ubiquinone; Thiamine; 3,4-dihydroxyphenylethanol
• Other Study ID Numbers: 200911781