Regulation of Lipid Metabolism in Autoimmune Disease: Multiple Sclerosis

• Conditions: Multiple Sclerosis
• Interventions: Other: Blood sampling

• Registration Number: NCT04053374
• Lead Sponsor: University College, London

Brief Summary

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

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 Timeline

• Study Start: 2018-09-01
• Status Verified: 2019-08
• Study First Submitted: 2019-08-05
• Study First Submitted QC: 2019-08-09
• Study First Posted: 2019-08-12
• Last Update Submitted: 2020-04-22
• Last Update Posted: 2020-04-24
• Primary Completion: 2020-06
• Study Completion: 2020-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 275

Inclusion Criteria

• 1. 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.
• 2. Having given written informed consent prior to undertaking any study-related procedures.
• 3. 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.
• 4. 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

• 1. Patients currently taking statins or other lipid lowering therapies.
• 2. Under any administrative or legal supervision.
• 3. 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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
DMD treatment naive CIS or RRMS patients	Blood sampling	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.
Disease controls	Blood sampling	People who undergo lumbar puncture due to clinical suspicion of neurological condition, but brain Magnetic Resonance Imaging (MRI) and CSF examination exclude MS diagnosis.
Primary Progressive Multiple Sclerosis (PPMS)	Blood sampling	People with confirmed diagnosis of PPMS
Healthy donors	Blood sampling	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.
DMD-treated with stable disease	Blood sampling	People with Multiple Sclerosis (MS) who are treated with DMD who have had stable disease symptoms for at least 3 months
Secondary Progressive Multiple Sclerosis (SPMS)	Blood sampling	People with confirmed diagnosis of SPMS

Primary Outcome Measures

Name	Time	Method
Analysis of serum	4 hours from point of sample collection	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.
Lipid Phenotyping (2)	4 hours from point of sample collection	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)
Analysis of immune cell function (2)	4 hours from point of sample collection	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.
Analysis of cytokine	4 hours from point of sample collection	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.
Analysis of immune cell function (1)	4 hours from point of sample collection	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.
Lipid Phenotyping (1)	4 hours from point of sample collection	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
Analysis of immune cell function	4 hours from point of sample collection	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.

Trial Locations

Locations (2)

National Hospital for Neurology and Neurosurgery; 🇬🇧 London, United Kingdom

University College London Hospitals NHS Foundation Trust; 🇬🇧 London, United Kingdom