Calorie Restriction in Multiple Sclerosis
Calorie Restriction as a Novel Therapeutic Tool to Manipulate Immunity and Improve Therapeutic Potential of First Line Drug Treatments During Relapsing Remitting Multiple Sclerosis
What it found
A paper reports the results; we have not read it yet. See Papers below.
What was tested
Treatment tested
- Caloric restriction
- Caloric restriction without cow's milk and gluten
What it measured
Main measures
Change of the "no evident disease activity" (NEDA) from baseline clinical status of MS patients at 6, 12, and 24 months
T0: before intervention, T1: after 6 months of intervention, T2: after 12 months of intervention, T3: after 24 months of intervention
Disability progressionRelapses
Other measures (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
Immune responseMitotic 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
VisionGlycolytic 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
How the body handles the medicineChange in the expression level of molecules involved in the signalling pathway of T-cell receptor (TCR)
T0: before intervention, T1: after 6 months of intervention, T2: after 12 months of intervention, T3: after 24 months of intervention
Change in the composition of the gut microbiota
T0: before intervention, T1: after 6 months of intervention, T2: after 12 months of intervention, T3: after 24 months of intervention
Who could take part
Relapsing MS · 18 to 60 · EDSS 0 to 5.5
Show the full criteria
Inclusion criteria
* 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.
Exclusion criteria
* 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.
As registered. Criteria can change, so ask the trial team or your neurologist.
About this trial
In the sponsor's words
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.
Papers
Results
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.Results
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.Results
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.Results
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.
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History
Started
Jul 2020
Main results due
Sept 2025
Finished
Sept 2025