A Pilot Study of Intermittent Calorie Restriction in Multiple Sclerosis

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 Overview

• Status: Completed
• Conditions: Relapsing Remitting Multiple Sclerosis
• Intervention / Treatment: Other: Diet

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18-50
• Capable of storing food safely, willing to follow diet/eat provided food, and able to receive shipments at home or work
• Meets 2010 criteria for McDonald MS;
• Relapse or new lesion in previous 2 years
• Expanded disability status score (EDSS) < 6
• Disease duration ≤15 years
• Untreated or on stable on first-line MS therapy [injectable] for at least 6 months, with no anticipated changes in the next 10 weeks
• Unchanged vitamin D dose or thyroid replacement dose (for those on it) with no anticipated changes or in supplement use for the next 10 weeks.
• Non-regular smoker (average no more than 1 cigarette/day) for at least 2 months
• Stable weight, by self report, for past 3 months (± 8 lbs)
• Body mass index (BMI) > 23 kg/m2

Exclusion Criteria:

• Pregnant or nursing, or unwilling to prevent pregnancy (if of childbearing to potential)

  • History of gastrointestinal disease causing malabsorption
  • History of diabetes requiring medication
  • History of stage IV/V chronic kidney disease or vascular disease
  • History of major surgery in past 3 months
  • Current use of warfarin
  • History of eating disorder
  • Currently on a special diet for MS/other diet (provided diet will be pork free)
  • Chemotherapy within the past year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Continuous calorie restriction; Participants will be provided with a diet that includes approximately 78% of calories each day that would be needed to maintain current BMI.	Other: Diet; Diet, standardized to the 50th percentile for macronutrients, will be provided at varied calorie levels as described.
Experimental: Intermittent calorie restriction; Participants will be provided a diet that with a daily calorie intake required to maintain current BMI, except only 25% of this calorie intake will be provided for 2 days a week.	Other: Diet; Diet, standardized to the 50th percentile for macronutrients, will be provided at varied calorie levels as described.
Placebo Comparator: Control calorie intake; Participants will be assigned to consume enough calories each day required to maintain current BMI	Other: Diet; Diet, standardized to the 50th percentile for macronutrients, will be provided at varied calorie levels as described.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Adverse events will be categorized by organ system and by the blinded neurologist's assessment of the relation to the diet.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	48 weeks
Quality of Life Questionnaire	"Functional Assessment in MS" results will be assessed during the study	48 weeks
NIH Patient-Reported-Outcomes Measurement Information System (PROMIS )Fatigue Questionnaire	PROMIS Fatigue results will be assessed during the study	48 weeks
Change in metabolite ratios	The impact of each calorie restriction diet versus control diet on the metabolomics profile will be assessed.	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.	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.	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.	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.	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.	8 weeks

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Ellen Mowry, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: December 28, 2015
• First Submitted That Met QC Criteria: January 4, 2016
• First Posted (Estimate): January 6, 2016

Study Record Updates

• Last Update Posted (Actual): November 17, 2017
• Last Update Submitted That Met QC Criteria: November 14, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• 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; Sclerosis; Multiple Sclerosis, Relapsing-Remitting
• Other Study ID Numbers: IRB00065806