Calorie Restriction in Multiple Sclerosis Patients

NCT02411838 | Completed

• 1 other identifier: 201307106
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hypothesize that adipokine (soluble molecules produced by the adipose tissue) levels are altered in MS compared to control subjects. Additionally, the investigators hypothesize that calorie restriction (CR) will improve clinical recovery from an MS relapse, ameliorate the adipokine and metabolic-inflammatory profile in MS, and enhance immune-regulatory mechanisms. This is a pilot study to determine the effects of CR in MS patients during an acute MS relapse (Acute CR phase) and for 6 months afterwards (Chronic CR phase). Calorie restriction will be achieved by following a regimen of alternate day fasting. The investigators will evaluate clinical outcomes and blood biomarkers at different time points.

Conditions

Multiple Sclerosis

Keywords

Multiple sclerosis; calorie restriction; adipokines

Outcome Measures

Primary Outcomes (4)

• Blood biomarkers

  Serum levels of: adipokines (leptin, adiponectin and resistin)

  After two weeks, 3 and 6 months

• Blood biomarkers

  Pro-inflammatory cytokines (IL-6, TNFalpha),

  After two weeks, 3 and 6 months

• Blood biomarker

  cortisol

  After two weeks, 3 and 6 months

• Blood biomarker

  T regulatory cell number and in vitro function

  After two weeks, 3 and 6 months

Secondary Outcomes (5)

• Clinical - Disability on the Expanded Disability Status Scale (EDSS)

  Two weeks, 3 and 6 months

• Clinical-Ambulation, hand and cognitive functions on the Multiple Sclerosis Functional Composite (MSFC) scale

  Two weeks, 3 and 6 months

• Clinical - Cognitive functions using the Symbol Digit Modality Test (SDMT).

  Two weeks, 3 and 6 months

• Clinical - Quality of life on the Multiple Sclerosis Quality of Life Inventory (MSQLI).

  Two weeks, 3 and 6 months

• Gut microbiome changes ( stool sample )

  Two weeks, 3 and 6 months

Study Arms (2)

Control group

NO INTERVENTION

Steroid treatment (10 total days), which is a standard therapy for significant MS relapses.

Calorie restriction

EXPERIMENTAL

The intervention in this group will be to undergo a regimen of calorie restriction through fasting every other day (named "alternate day fasting"). Specifically this group will undergo alternate day fasting plus the same steroid regimen as the control group (CR GROUP). During the day of fasting the subject will be allowed to eat two salads with light dressing, not to go over approximately 500 calories. The CR group subjects will fast on day 2 (second day of IVMP) and then continue to fast on alternate days until day 15. This is the end of the Acute CR phase of the Study, and patients may discontinue the study at this point.

Other: Calorie restriction

Interventions

Calorie restriction OTHER

Calorie restriction will be achieved by alternate day fasting. During the day of fasting the subject will be allowed to eat two salads with light dressing, not to go over approximately 500 calories. The CR group subjects will fast on day 2 (second day of steroids) and then continue to fast on alternate days until day 15. This is the end of the Acute CR phase of the Study, and patients may discontinue the study at this point. Chronic CR phase At the end of the Acute CR phase, both groups will be offered to enroll in the alternate day fasting regimen for 6 months (Chronic CR phase). During this phase, patients with a BMI \<28 will follow a regimen of fasting for two days per week while patients with BMI\>28 will follow a regimen of fasting for three days per week.

Calorie restriction

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants must be diagnosed with relapsing MS.
• Participants must be 18 - 60 years old.
• Participants will need to be experiencing a relapse as identified by their neurologist.
• Participants must have body mass index (BMI) of 23 or higher.
• Participants must not have other ongoing diseases in other systems.

You may not qualify if:

• History of any chronic disease process (excluding MS) that could interfere with interpretation of results.
• Use of insulin pumps or insulin injections for diabetes.
• Use of drugs like Warfarin or Coumadin that need to monitor the intake of vegetables containing high levels of vitamin K.
• Patients that are required by a physician to follow a special diet or food restriction (diabetic, gastric bypass, soft/pureed food, etc.)
• Alcoholism, psychiatric problems, life situations that would interfere with study participation and compliance.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University in St Louis

St Louis, Missouri, 63110, United States

Location

Related Publications (4)

• Piccio L, Cantoni C, Henderson JG, Hawiger D, Ramsbottom M, Mikesell R, Ryu J, Hsieh CS, Cremasco V, Haynes W, Dong LQ, Chan L, Galimberti D, Cross AH. Lack of adiponectin leads to increased lymphocyte activation and increased disease severity in a mouse model of multiple sclerosis. Eur J Immunol. 2013 Aug;43(8):2089-100. doi: 10.1002/eji.201242836. Epub 2013 Jun 7.

  PMID: 23640763 BACKGROUND

• Piccio L, Stark JL, Cross AH. Chronic calorie restriction attenuates experimental autoimmune encephalomyelitis. J Leukoc Biol. 2008 Oct;84(4):940-8. doi: 10.1189/jlb.0208133. Epub 2008 Aug 4.

  PMID: 18678605 BACKGROUND

• Allaf M, Elghazaly H, Mohamed OG, Fareen MFK, Zaman S, Salmasi AM, Tsilidis K, Dehghan A. Intermittent fasting for the prevention of cardiovascular disease. Cochrane Database Syst Rev. 2021 Jan 29;1(1):CD013496. doi: 10.1002/14651858.CD013496.pub2.

  PMID: 33512717 DERIVED

• Cignarella F, Cantoni C, Ghezzi L, Salter A, Dorsett Y, Chen L, Phillips D, Weinstock GM, Fontana L, Cross AH, Zhou Y, Piccio L. Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota. Cell Metab. 2018 Jun 5;27(6):1222-1235.e6. doi: 10.1016/j.cmet.2018.05.006.

  PMID: 29874567 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Caloric Restriction

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Laura Piccio, MD, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Anne H Cross, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Assistamt Professor

Study Record Dates

• First Submitted: December 5, 2013
• First Posted: April 8, 2015
• Study Start: February 1, 2014
• Primary Completion: December 1, 2016
• Study Completion: June 1, 2017
• Last Updated: May 29, 2020

Record last verified: 2020-05

Locations

US (1)