Experimental studies of the experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, indicate that the number of calories fed to mice prevent EAE and are also associated with less severe disease in mice who do develop the disease. Currently, whether these results translate favorably in humans is unknown. This is a pilot trial of testing two caloric restriction (CR) diets versus a control diet in multiple sclerosis (MS) patients: one continuous caloric restriction (CR) diet where a small number of calories will be restricted every day or another intermittent CR diet where a caloric intake will be restricted more severely 2 days per week. Participants are randomized to one of the diets, and for the first 8 weeks, will receive standardized, prepared meals tailored to the specific diet. At the conclusion of the controlled feeding study, all participants will transition to an unblinded phase for an additional 40 weeks where they are provided with instructions to follow an intermittent CR diet.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
36
Diet, standardized to the 50th percentile for macronutrients, will be provided at varied calorie levels as described.
Johns Hopkins University
Baltimore, Maryland, United States
Adverse events
Adverse events will be categorized by organ system and by the blinded neurologist's assessment of the relation to the diet.
Time frame: 8 weeks
Adherence to Calories Assigned
Adherence will be assessed by comparing the total caloric intake provided to the patients through the assigned diet to the total energy intake determined by the research dieticians.
Time frame: 8 weeks
Adherence to Calories Assigned
Adherence during the "advice-only" phase will be compared to adherence in each diet group during the first 8 weeks using paired t-tests, where the grouping is done naturally by subject.
Time frame: 48 weeks
Adverse Events
Adverse events will be categorized by organ system and by the blinded neurologist's assessment of the relation to the diet.
Time frame: 48 weeks
Quality of Life Questionnaire
"Functional Assessment in MS" results will be assessed during the study
Time frame: 48 weeks
NIH Patient-Reported-Outcomes Measurement Information System (PROMIS )Fatigue Questionnaire
PROMIS Fatigue results will be assessed during the study
Time frame: 48 weeks
Change in metabolite ratios
The impact of each calorie restriction diet versus control diet on the metabolomics profile will be assessed.
Time frame: 8 weeks
Immune cell subsets/cytokines
The impact of each calorie restriction diet versus control diet on ratios of immune cell subsets (e.g. T-helper (TH)17, TH1, TH2, T regulatory) and related cytokines will be assessed.
Time frame: 8 weeks
Change in concentration of measures of metabolism
The impact of each calorie restriction diet versus control diet on fasting glucose, insulin, leptin, ghrelin, C-reactive protein, lipids, and long-chain ceramides will be assessed.
Time frame: 8 weeks
Change in serum lipid concentration
The impact of each calorie restriction diet versus control diet on fasting lipids and long-chain ceramides will be assessed.
Time frame: 8 weeks
Change in serum brain-derived neurotrophic factor concentration (BDNF)
The impact of each calorie restriction diet versus control diet on fasting BDNF will be assessed.
Time frame: 8 weeks
Change in levels of oxidative stress biomarkers
The impact of each calorie restriction diet versus control diet on protein carbonyls, 8-isoprostane, nitrotyrosine, and 4-hydroxynonenal adducts will be assessed.
Time frame: 8 weeks
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