Regulation of Lipid Metabolism in Autoimmune Disease: Multiple Sclerosis

NCT ID: NCT04053374

Last Updated: 2020-04-24

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 275 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-09-01
• Study Completion Date: 2020-06-30

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.

Conditions

Multiple Sclerosis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

Blood sampling

Intervention Type: OTHER

Blood sampling +/- CSF sampling

Secondary Progressive Multiple Sclerosis (SPMS)

People with confirmed diagnosis of SPMS

Blood sampling

Intervention Type: OTHER

Blood sampling +/- CSF sampling

Primary Progressive Multiple Sclerosis (PPMS)

People with confirmed diagnosis of PPMS

Blood sampling

Intervention Type: OTHER

Blood sampling +/- 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

Blood sampling

Intervention Type: OTHER

Blood sampling +/- 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.

Blood sampling

Intervention Type: OTHER

Blood sampling +/- 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.

Blood sampling

Intervention Type: OTHER

Blood sampling +/- CSF sampling

Interventions

Blood sampling

Blood sampling +/- CSF sampling

Intervention Type: OTHER

Other Intervention Names

CSF sampling

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University College London Hospitals

OTHER

Sponsor Role: collaborator

University College, London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rachel Farrell, Dr

Role: PRINCIPAL_INVESTIGATOR

UCL & University College London Hospitals NHS Foundation Trust

Locations

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status: RECRUITING

National Hospital for Neurology and Neurosurgery

London, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Liz Jury, Prof

Role: CONTACT

e.jury@ucl.ac.uk

02031082161

Kirsty Waddington, Dr

Role: CONTACT

kirsty.waddington.13@ucl.ac.uk

02031082167

Facility Contacts

Kirsty Waddington, Dr

Role: primary

kirsty.waddington.13@ucl.ac.uk

02031082167

Rachel Farrell, Dr

Role: primary

rachel.farrell@ucl.ac.uk

02034483561

Other Identifiers

18/0057

Identifier Type: -

Identifier Source: org_study_id