Regulation of Lipid Metabolism in Autoimmune Disease: Multiple Sclerosis

Multiple Sclerosis Clinical Trial

— RELOAD-MS  

Official title:

Regulation of Lipid Metabolism in Autoimmune Disease: Multiple Sclerosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04053374
• Other study ID #: 18/0057
• Status: Recruiting
• Start date: September 1, 2018
• Est. completion date: June 2020

Study information

• Verified date: August 2019
• Source: University College, London
• Contact: Liz Jury, Prof
• Phone: 02031082161
• Email: e.jury[@]ucl.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 275
• Est. completion date: June 2020
• Est. primary completion date: June 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Autoimmune Diseases
• Multiple Sclerosis
• Sclerosis

Intervention

Other:
• Blood sampling
Blood sampling +/- CSF sampling

Locations

Country	Name	City	State
United Kingdom	National Hospital for Neurology and Neurosurgery	London
United Kingdom	University College London Hospitals NHS Foundation Trust	London

Sponsors (2)

Lead Sponsor	Collaborator
University College, London	University College London Hospitals

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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