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

Phase 1

Completed

• Conditions: Multiple Sclerosis

• Registration Number: NCT01381354
• Lead Sponsor: University of Iowa

Brief Summary

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

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 Timeline

• Study Start: 2010-10
• Study First Submitted: 2011-05-26
• Study First Submitted QC: 2011-06-24
• Study First Posted: 2011-06-27
• Primary Completion: 2016-02
• Study Completion: 2016-05
• Status Verified: 2018-06
• Last Update Submitted: 2018-06-22
• Last Update Posted: 2018-06-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 38

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Fatigue severity scale	Baseline, 3 M, 6M, 9M,12 M	Self reported fatigue severity scale, (agreement with 9 questions describing impact of fatigue on daily activities)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Univeristy of Iowa/ VA Iowa City VA Medical Center; 🇺🇸 Iowa City, Iowa, United States