Regulation of Lipid Metabolism in Autoimmune Disease: Multiple Sclerosis (RELOAD-MS)
22. april 2020 opdateret af: University College, London
The aim of this research is to understand how lipids such as cholesterol affect the disease process in people with MS.
Studieoversigt
Detaljeret beskrivelse
In Multiple Sclerosis (MS) immune cells recognise myelin, the coating around nerve fibres, as a foreign molecule and attack it by mistake; at the same time regulatory immune cells (which are normally protective) do not work properly and cannot block the harmful effects of the activated immune cells effectively.
Immune cells work via a complex system of signals that start on the outside layer of the cell (the plasma membrane), these signals are transmitted inside the cell where they trigger immune cell activation. The plasma membrane consists of a fatty layer and changes in the type of fat in the membrane can affect immune cell signalling and immune cell function.
The aims of this project are to:
- Identify what is different about the types of fat in immune cells from healthy donors and people with MS and identify what triggers the production of these different types of fat.
- Identify how different types of fat control immune cell function in healthy donors and people with MS
- Identify possible ways to regulate the type of fat in immune cell membranes to restore normal immune cell function in MS.
Methods: This research study involves collecting participant demographic and clinical information, blood and Cerebral Spinal Fluid (CSF) (optional) from patients with MS. Blood will also be collected from healthy volunteers for comparison. Experiments will be performed on the blood samples and the results correlated with the clinical and disease features of patients.
Outcomes: Many of the molecules involved in the generation of fats are well known and for some of them drugs are already used in humans to treat diseases (for example statins). This could allow the rapid translation of the results from this study to the clinic and have a direct impact for people with MS.
Undersøgelsestype
Observationel
Tilmelding (Forventet)
275
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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London, Det Forenede Kongerige, NW1 2BU
- Rekruttering
- University College London Hospitals NHS Foundation Trust
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Kontakt:
- Kirsty Waddington, Dr
- Telefonnummer: 02031082167
- E-mail: kirsty.waddington.13@ucl.ac.uk
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London, Det Forenede Kongerige, WC1N 3BG
- Rekruttering
- National Hospital For Neurology and Neurosurgery
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Kontakt:
- Rachel Farrell, Dr
- Telefonnummer: 02034483561
- E-mail: rachel.farrell@ucl.ac.uk
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år til 80 år (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ja
Køn, der er berettiget til at studere
Alle
Prøveudtagningsmetode
Ikke-sandsynlighedsprøve
Studiebefolkning
Those with and those without MS
Beskrivelse
Inclusion Criteria:
- 01. Male and female patients of between 18 years and 80 years of age with a diagnosis of MS or CIS.
- Diagnosis confirmed according to the standards at the time when diagnosis was made.
- Patients not receiving biological DMDs within the previous 3 months OR
- Patients treated with DMDs (Interferon beta (Rebif, Betaferon, Avonex, Plegridy), Glatiramer Acetate (Copaxone), Dimethylfumarate (Tecfidera), Fingolimod (Gilenya), Teriflunomide (Aubagio), Natalizumab (Tysabri),) Alemtuzumab (Lemtrada), immunosuppressive drugs (azathioprine, cyclophosphamide etc) who have stable disease in the last 3 months.
- Last course of corticosteroids more than three months ago.
- 02. Having given written informed consent prior to undertaking any study-related procedures.
- 03. Covered by a health insurance system where applicable, and/or in compliance with the recommendations of the national laws in force relating to biomedical research.
- 04. Healthy donors ONLY : Male and female donors of between 18 years and 80 years of age in good health and not aware of any diagnosis of an autoimmune condition.
Exclusion Criteria:
- 01. Patients currently taking statins or other lipid lowering therapies.
- 02. Under any administrative or legal supervision.
- 03. Conditions/situations such as:
- Patients with conditions/concomitant diseases making them non evaluable for the primary endpoint
- Impossibility to meet specific protocol requirements (e.g. blood sampling)
- Patient is the Investigator or any sub investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol
- Uncooperative or any condition that could make the patient potentially non-compliant to the study procedures
- Pregnant or breast-feeding women, currently or in the last three months prior to inclusion
- Patients who have been vaccinated in the last three months prior to inclusion
Healthy donors ONLY: will be excluded from the study if:
- Donors with a condition likely to influence your blood results such as a current infection or cancer
- Donors who are pregnant or breast-feeding currently or in the last three months
- Donors who have been vaccinated within the last three months
- Donors who cannot provide a blood sample
- Donors who are unable to give informed consent
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
Kohorter og interventioner
Gruppe / kohorte |
Intervention / Behandling |
|---|---|
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DMD treatment naive CIS or RRMS patients
Newly presenting Clinically Isolated Syndrome (CIS) or Relapsing and Remitting Multiple Sclerosis (RRMS) patients not treated before with Disease Modifying Drugs (DMD) Additional analysis of CSF and CSF cells will be performed in this cohort on a voluntary basis.
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Blood sampling +/- CSF sampling
Andre navne:
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Secondary Progressive Multiple Sclerosis (SPMS)
People with confirmed diagnosis of SPMS
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Blood sampling +/- CSF sampling
Andre navne:
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Primary Progressive Multiple Sclerosis (PPMS)
People with confirmed diagnosis of PPMS
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Blood sampling +/- CSF sampling
Andre navne:
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DMD-treated with stable disease
People with Multiple Sclerosis (MS) who are treated with DMD who have had stable disease symptoms for at least 3 months
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Blood sampling +/- CSF sampling
Andre navne:
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Disease controls
People who undergo lumbar puncture due to clinical suspicion of neurological condition, but brain Magnetic Resonance Imaging (MRI) and CSF examination exclude MS diagnosis.
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Blood sampling +/- CSF sampling
Andre navne:
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Healthy donors
Age, sex and ethnicity matched healthy donors will also be recruited from university and hospital staff and patient friends after informed consent has been obtained.
Healthy donors will be asked to provide a blood sample and demographic information but will NOT be asked to provide CSF samples.
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Blood sampling +/- CSF sampling
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Lipid Phenotyping (1)
Tidsramme: 4 hours from point of sample collection
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Blood samples collected from consented participants containing the peripheral blood mononuclear cells (PBMC), serum, Deoxyribonucleic Acid (DNA) and CSF/CSF cells will be appropriately sent to Dr Elizabeth Jury, Centre for Rheumatology Research, University College London (UCL), Rayne Building for lipid phenotyping of PBMC using flow cytometry
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4 hours from point of sample collection
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Lipid Phenotyping (2)
Tidsramme: 4 hours from point of sample collection
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Blood samples collected from consented participants containing the peripheral blood mononuclear cells (PBMC), serum, Deoxyribonucleic Acid (DNA) and CSF/CSF cells will be appropriately sent to Dr Elizabeth Jury, Centre for Rheumatology Research, University College London, Rayne Building for lipid phenotyping of PBMC using measurement of quantitative polymerase chain reaction (qPCR)
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4 hours from point of sample collection
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Analysis of immune cell function
Tidsramme: 4 hours from point of sample collection
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Blood samples collected from consented participants containing the peripheral blood mononuclear cells (PBMC), serum, Deoxyribonucleic Acid (DNA) and CSF/CSF cells will be appropriately sent to Dr Elizabeth Jury, Centre for Rheumatology Research, University College London, Rayne Building for analysis of immune cell function using flow cytometry.
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4 hours from point of sample collection
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Analysis of cytokine
Tidsramme: 4 hours from point of sample collection
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Blood samples collected from consented participants containing the peripheral blood mononuclear cells (PBMC), serum, Deoxyribonucleic Acid (DNA) and CSF/CSF cells will be appropriately sent to Dr Elizabeth Jury, Centre for Rheumatology Research, University College London, Rayne Building for analysis of cytokine using flow cytometry.
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4 hours from point of sample collection
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Analysis of immune cell function (1)
Tidsramme: 4 hours from point of sample collection
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Blood samples collected from consented participants containing the peripheral blood mononuclear cells (PBMC), serum, Deoxyribonucleic Acid (DNA) and CSF/CSF cells will be appropriately sent to Dr Elizabeth Jury, Centre for Rheumatology Research, University College London, Rayne Building for analysis of immune cell function through cell culture.
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4 hours from point of sample collection
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Analysis of immune cell function (2)
Tidsramme: 4 hours from point of sample collection
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Blood samples collected from consented participants containing the peripheral blood mononuclear cells (PBMC), serum, Deoxyribonucleic Acid (DNA) and CSF/CSF cells will be appropriately sent to Dr Elizabeth Jury, Centre for Rheumatology Research, University College London, Rayne Building for analysis of immune cell function through flow cytometry.
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4 hours from point of sample collection
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Analysis of serum
Tidsramme: 4 hours from point of sample collection
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Blood samples collected from consented participants containing serum will be appropriately sent to Dr Elizabeth Jury, Centre for Rheumatology Research, University College London, Rayne Building for measurement of chemokine, lipid expression and expression of other molecules important for immune cell activation.
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4 hours from point of sample collection
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Rachel Farrell, Dr, UCL & University College London Hospitals NHS Foundation Trust
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Faktiske)
1. september 2018
Primær færdiggørelse (Forventet)
1. juni 2020
Studieafslutning (Forventet)
1. juni 2020
Datoer for studieregistrering
Først indsendt
5. august 2019
Først indsendt, der opfyldte QC-kriterier
9. august 2019
Først opslået (Faktiske)
12. august 2019
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
24. april 2020
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
22. april 2020
Sidst verificeret
1. august 2019
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- 18/0057
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
UBESLUTET
IPD-planbeskrivelse
All participants indicate by written consent if they are willing to allow any of their un-used samples and associated data to be used for future research MS related research.
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