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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04053374
Recruitment Status : Recruiting
First Posted : August 12, 2019
Last Update Posted : August 12, 2019
Sponsor:
Collaborator:
University College London Hospitals NHS Foundation Trust
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment
Multiple Sclerosis 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.

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Study Type : Observational
Estimated Enrollment : 275 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Regulation of Lipid Metabolism in Autoimmune Disease: Multiple Sclerosis
Actual Study Start Date : September 1, 2018
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine


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 Name: CSF sampling

Secondary Progressive Multiple Sclerosis (SPMS)
People with confirmed diagnosis of SPMS
Other: Blood sampling
Blood sampling +/- CSF sampling
Other Name: CSF sampling

Primary Progressive Multiple Sclerosis (PPMS)
People with confirmed diagnosis of PPMS
Other: Blood sampling
Blood sampling +/- CSF sampling
Other Name: 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 Name: 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 Name: 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 Name: CSF sampling




Primary Outcome Measures :
  1. Lipid Phenotyping (1) [ Time Frame: 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

  2. Lipid Phenotyping (2) [ Time Frame: 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)

  3. Analysis of immune cell function [ Time Frame: 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.

  4. Analysis of cytokine [ Time Frame: 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.

  5. Analysis of immune cell function (1) [ Time Frame: 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.

  6. Analysis of immune cell function (2) [ Time Frame: 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.

  7. Analysis of serum [ Time Frame: 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.


Biospecimen Retention:   Samples With DNA
Blood sample Cerebral Spinal Fluid (CSF) sample


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Those with and those without MS
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04053374


Contacts
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Contact: Liz Jury, Prof 02031082161 e.jury@ucl.ac.uk
Contact: Kirsty Waddington, Dr 02031082167 kirsty.waddington.13@ucl.ac.uk

Locations
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United Kingdom
University College London Hospitals NHS Foundation Trust Recruiting
London, United Kingdom, NW1 2BU
Contact: Kirsty Waddington, Dr    02031082167    kirsty.waddington.13@ucl.ac.uk   
National Hospital for Neurology and Neurosurgery Recruiting
London, United Kingdom, WC1N 3BG
Contact: Rachel Farrell, Dr    02034483561    rachel.farrell@ucl.ac.uk   
Sponsors and Collaborators
University College, London
University College London Hospitals NHS Foundation Trust
Investigators
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Principal Investigator: Rachel Farrell, Dr UCL & University College London Hospitals NHS Foundation Trust

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Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT04053374    
Other Study ID Numbers: 18/0057
First Posted: August 12, 2019    Key Record Dates
Last Update Posted: August 12, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Sclerosis
Autoimmune Diseases
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Immune System Diseases