Regulation of Lipid Metabolism in Autoimmune Disease: Multiple Sclerosis (RELOAD-MS)

The aim of this research is to understand how lipids such as cholesterol affect the disease process in people with MS.

Study Overview

• Status: Unknown
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Other: Blood sampling

Detailed Description

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:

1. 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.
2. Identify how different types of fat control immune cell function in healthy donors and people with MS
3. 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.

• Study Type: Observational
• Enrollment (Anticipated): 275

Contacts and Locations

• Study Contact: Name: Liz Jury, Prof; Phone Number: 02031082161; Email: e.jury@ucl.ac.uk
• Study Contact Backup: Name: Kirsty Waddington, Dr; Phone Number: 02031082167; Email: kirsty.waddington.13@ucl.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, NW1 2BU
    • Recruiting
    • University College London Hospitals NHS Foundation Trust
    • Contact: Kirsty Waddington, Dr; Phone Number: 02031082167; Email: kirsty.waddington.13@ucl.ac.uk
  • London, United Kingdom, WC1N 3BG
    • Recruiting
    • National Hospital For Neurology and Neurosurgery
    • Contact: Rachel Farrell, Dr; Phone Number: 02034483561; Email: rachel.farrell@ucl.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Those with and those without MS

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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.	Other: Blood sampling; Blood sampling +/- CSF sampling; Other Names: CSF sampling
Secondary Progressive Multiple Sclerosis (SPMS); People with confirmed diagnosis of SPMS	Other: Blood sampling; Blood sampling +/- CSF sampling; Other Names: CSF sampling
Primary Progressive Multiple Sclerosis (PPMS); People with confirmed diagnosis of PPMS	Other: Blood sampling; Blood sampling +/- CSF sampling; Other Names: CSF sampling
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	Other: Blood sampling; Blood sampling +/- CSF sampling; Other Names: CSF sampling
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.	Other: Blood sampling; Blood sampling +/- CSF sampling; Other Names: CSF sampling
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.	Other: Blood sampling; Blood sampling +/- CSF sampling; Other Names: CSF sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipid Phenotyping (1)	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	4 hours from point of sample collection
Lipid Phenotyping (2)	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)	4 hours from point of sample collection
Analysis of immune cell function	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.	4 hours from point of sample collection
Analysis of cytokine	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.	4 hours from point of sample collection
Analysis of immune cell function (1)	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.	4 hours from point of sample collection
Analysis of immune cell function (2)	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.	4 hours from point of sample collection
Analysis of serum	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.	4 hours from point of sample collection

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: University College London Hospitals
• Investigators: Principal Investigator: Rachel Farrell, Dr, UCL & University College London Hospitals NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Anticipated): June 1, 2020
• Study Completion (Anticipated): June 1, 2020

Study Registration Dates

• First Submitted: August 5, 2019
• First Submitted That Met QC Criteria: August 9, 2019
• First Posted (Actual): August 12, 2019

Study Record Updates

• Last Update Posted (Actual): April 24, 2020
• Last Update Submitted That Met QC Criteria: April 22, 2020
• Last Verified: August 1, 2019

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; Multiple Sclerosis; Sclerosis; Autoimmune Diseases
• Other Study ID Numbers: 18/0057

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No