Calorie Restriction in Multiple Sclerosis

NCT04042415 | Active Not Recruiting

• 1 other identifier: FISM 2018/S/5
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 1

Brief Summary

There is a strong relationship between metabolic state and immune tolerance through a direct control exerted on immune cells by specific intracellular nutrient-energy sensors. An increased "metabolic work load" represents a novel issue linking metabolism with loss of self-immune tolerance. Several disease-modifying drugs have been approved for Relapsing-remitting Multiple Sclerosis (RR-MS) treatments and have shown to reduce relapse rates by modulating immune responses; however, their impact on long-term disease progression and accrual of irreversible neurological disability remains largely unclear, underlining the need for novel therapeutic strategies. In this context, both acute fasting (AF) and chronic caloric restriction (CR) have been shown to improve experimental autoimmune encephalomyelitis (EAE). Despite this evidence, no specific studies have been performed to dissect at the cellular level the mechanism of action of CR in the context of autoimmunity and MS. This study aims at investigating this specific point in order to pave the way for a wider utilization of a nutritional approach to alter MS progression and activity. The aim of this study is to improve the outcome of RR-MS and the efficacy of first line drug treatments (ie. Copaxone or Tecfidera) by altering the metabolic state of the host via calorie restriction with the aim to re-equilibrate immune/inflammatory responses of patients.

Conditions

Multiple Sclerosis, Relapsing-Remitting; Caloric Restriction

Keywords

Multiple Sclerosis; Immuno-metabolism; Calorie restriction; Treg cells; Inflammation

Outcome Measures

Primary Outcomes (1)

• Change of the "no evident disease activity" (NEDA) from baseline clinical status of MS patients at 6, 12, and 24 months

  Evaluation of the "no evident disease activity" (NEDA) defined thanks to the evaluation of three components: (i) absence of confirmed disability progression (CDP), (ii) absence of relapses and (iii) absence of radiological activity before and after starting caloric restricted diet.

  T0: before intervention, T1: after 6 months of intervention, T2: after 12 months of intervention, T3: after 24 months of intervention

Secondary Outcomes (7)

• Percentage of different immune cells populations (circulating immune cells, regulatory T cells, conventional T cells, etc.)

  T0: before intervention, T1: after 6 months of intervention, T2: after 12 months of intervention, T3: after 24 months of intervention

• Mitotic cell divisions of conventional T cells

  T0: before intervention, T1: after 6 months of intervention, T2: after 12 months of intervention, T3: after 24 months of intervention

• Glycolytic metabolism of T cells (mpH/min)

  T0: before intervention, T1: after 6 months of intervention, T2: after 12 months of intervention, T3: after 24 months of intervention

• Oxidative metabolism of T cells (pMol/min)

  T0: before intervention, T1: after 6 months of intervention, T2: after 12 months of intervention, T3: after 24 months of intervention

• Circulating adipokines (pg/ml)

  T0: before intervention, T1: after 6 months of intervention, T2: after 12 months of intervention, T3: after 24 months of intervention

Study Arms (3)

Free diet controls

NO INTERVENTION

Patients on free diet

Caloric restriction

EXPERIMENTAL

Patients will be treated with a mild caloric restriction (15-20% caloric restriction)

Other: Caloric restriction

Caloric restriction without cow's milk and gluten

EXPERIMENTAL

Patients will be treated with a mild caloric restriction (15-20% caloric restriction) with exclusion of cow's milk, its derivatives and gluten

Other: Caloric restriction without cow's milk and gluten

Interventions

Caloric restriction OTHER

Patients will be treated with a diet regimen of mild caloric restriction (15-20% caloric restriction)

Caloric restriction

Caloric restriction without cow's milk and gluten OTHER

Patients will be treated with mild caloric restriction (15-20% caloric restriction) plus excluding from diet cow's milk, its derivatives and gluten.

Caloric restriction without cow's milk and gluten

Eligibility Criteria

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

You may qualify if:

• Subjects with early diagnosis (no more than 2 years) of RR-MS according to the revised McDonald (2017) criteria;
• Subjects naïve-to-treatment;
• Subjects with EDSS between 0-5.5;
• No use of oral or systemic corticosteroids or adrenocorticotropic hormone (ACTH) within 30 days prior to screening visit;
• Subjects with BMI \> 22 kg/m2 and BMI \< 28 kg/m2;
• Willing to collect a food diary for one week and to donate a blood and stool samples;
• No antibiotic treatment within 3 months of enrolment;
• No immunosuppressive therapy;
• Signed informed consent.

You may not qualify if:

• Pregnancy and breast-feeding;
• History of alcohol or drug abuse;
• Serious psychiatric disorders;
• Any major medical problem that in the opinion of the investigator could bias the results (e.g. HIV infection) or affect adherence to the protocol;
• Subjects with inadequate haematological function (defined by leukocyte ≤ 2,0 x 109; platelets \<100 x 109; haemoglobin \<12 g/dl for female and \<13 g/dl for male), liver function (defined by aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase \> 2.0 times upper limit of normal), thyroid function (according to physician's discretion);
• Known hypersensitivity to gadolinium;
• Any other condition that would prevent the subject from undergoing a contrast-enhanced MRI scan;
• Any contra-indication according to the specific first line treatment for MS.

Sponsors & Collaborators

• Federico II University: lead
• Fondazione Italiana Sclerosi Multipla: collaborator

Study Sites (1)

Neuromed - Istituto Neurologico Mediterraneo Pozzilli

Pozzilli, IS, 86077, Italy

Location

Related Publications (4)

• De Rosa V, La Cava A, Matarese G. Metabolic pressure and the breach of immunological self-tolerance. Nat Immunol. 2017 Oct 18;18(11):1190-1196. doi: 10.1038/ni.3851.

  PMID: 29044230 RESULT

• Sanna V, Di Giacomo A, La Cava A, Lechler RI, Fontana S, Zappacosta S, Matarese G. Leptin surge precedes onset of autoimmune encephalomyelitis and correlates with development of pathogenic T cell responses. J Clin Invest. 2003 Jan;111(2):241-50. doi: 10.1172/JCI16721.

  PMID: 12531880 RESULT

• Matarese G, Carrieri PB, La Cava A, Perna F, Sanna V, De Rosa V, Aufiero D, Fontana S, Zappacosta S. Leptin increase in multiple sclerosis associates with reduced number of CD4(+)CD25+ regulatory T cells. Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5150-5. doi: 10.1073/pnas.0408995102. Epub 2005 Mar 23.

  PMID: 15788534 RESULT

• De Rosa V, Procaccini C, La Cava A, Chieffi P, Nicoletti GF, Fontana S, Zappacosta S, Matarese G. Leptin neutralization interferes with pathogenic T cell autoreactivity in autoimmune encephalomyelitis. J Clin Invest. 2006 Feb;116(2):447-55. doi: 10.1172/JCI26523. Epub 2006 Jan 12.

  PMID: 16410832 RESULT

Related Links

• Laboratory site
• Italian MS Foundation official site with reference of the Calorie-MS study

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis; Inflammation

Interventions

Caloric Restriction; Milk; Glutens

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Beverages; Dairy Products; Food; Food and Beverages; Prolamins; Grain Proteins; Plant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Seed Storage Proteins

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Principal investigator

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: August 2, 2019
• Study Start: July 14, 2020
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: August 20, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)