MS Research

Studies at University of Nottingham

DECISIve: DiagnosE using the Central veIn SIgn. A prospective diagnostic superiority study comparing T2* MRI and lumbar puncture in patients presenting with possible Multiple Sclerosis.

Funded by NIHR Research for Patient Benefit. A number of patients complain that lumbar puncture is an invasive procedure and encouraged us to find a better way to diagnose MS. This research aims to change the way people are diagnosed with MS and reduce the number of lumbar punctures used. Our team will recruit a large number of people from different hospitals whose doctors suspect they may have MS. We will invite them to have a new MRI scan we have developed here in Nottingham and is based on the detection of a central vein in MS lesions, a very characteristic finding. We will compare the accuracy, speed, costs, and acceptability of the different tests needed to make a diagnosis of MS and establish if most lumbar punctures can be replaced by a slightly longer MRI scan. For more information please contact Clinical Research Fellow Dr Christopher Allen ([email protected])

AIMS: AI gets real: using routine clinical data and Artificial Intelligence to predict worsening of MS despite treatment.

Funded by MRC and NIHR. A wealth of clinical and MRI data from patients with MS are acquired every year in clinical practice, but only part of these data are used for clinical decision-making. We propose that a set of structural characteristics extracted from the MRI brain scans of people with MS are related to biological changes which are meaningful to MS, and may therefore act as predictive markers for the outcome. In this study, we aim to use whole-image brain MRI scans processed with AI techniques and detect the clinical and MRI profiles that predict the accumulation of MS-related disability or cognitive impairment. We will take advantage of our MS clinic and the Nottingham MS Society Register. Using clinical information which patients have consented for us to use, and the MRI images before starting treatment, we will train a computer to use mathematical models to predict whether a person’s MS will determine accumulating disability or cognitive impairment over the long term. Furthermore, we seek to see if the profile can predict the development of disability in other patient groups, by validating the models in large sets of MRI scans obtained from other groups of people with MS using different scanners. We will use a large group of patients from the United States and also align with a clinical trial ongoing in UK and US, which compares treatments for MS with different strengths. By identifying early, at diagnosis, who is likely to fare worse over the long term, we could offer them a more tailored treatment approach. For more information please contact Chief Investigator Dr Radu Tanasescu ([email protected]).

DELIVER-MS: Determining the Effectiveness of Early Intensive versus Escalation Approaches for the Treatment of Relapsing-Remitting Multiple Sclerosis.

Funded by PCORI. DELIVER-MS is a study coordinated by Nottingham and the Cleveland Clinic in the USA that is comparing two treatment strategies in 400 people with relapsing-remitting MS who have never taken a disease-modifying therapy. The study is currently recruiting across 30 centres in the United States and the United Kingdom. One strategy is an “escalation” approach, in which individuals start taking a less powerful therapy with the option of switching to a more potent therapy in the face of disease activity. The alternative treatment approach involves starting with a strong therapy that is potentially more effective but also carries a greater risk for significant adverse effects. For more information please contact Trial Manager Harriet Howard ([email protected]).

The SpINDLE study: Spinal cord, MS, & diabetes.

Funded by NUH Charity. Our group has pioneered the measurement of spinal cord atrophy in MS and its use in longitudinal studies of MS DMT. In the SpINDLE study, we are applying our imaging techniques to diabetes with or without neuropathy, in an attempt to determine whether spinal cord area/volume can be used as markers of disease progression. This allows us to compare changes and rates of atrophy with those of people with MS. For more information please contact Clinical Research Fellow Dr Afagh Garjani ([email protected]).

NEuRoMS: Neuropsychological Evaluation and Rehabilitation in Multiple Sclerosis.

Funded by NIHR Programme Grant for Applied Research. The NEuRoMS study is a 6-year program that aims to develop a neuropsychological evaluation pathway, to routinely assess all people with MS for cognitive problems attending NHS MS clinics, and to develop and test a brief neuropsychological rehabilitation program for people with MS with mild cognitive problems. For more information please contact Programme Manager Dr. Gogem Topcu ([email protected]).

Development of a self-report measure of cognitive abilities for people with MS.

Funded by Health Education England (as part of the DClinPsydegee). There are a few self-report measures of cognitive abilities for people with MS, but these tend to be long, complex, lack validity and input from people with MS, or are expensive. Therefore, we cannot use these in routine clinical practice in NHS MS clinics. Furthermore, increasingly, there is a call to use robust patient-reported measures in clinical trials. Therefore, it is vital that we have one that is suitable for use for these purposes. In this study, Heather will develop an item pool based on qualitative research into cognitive problems faced by people with MS, from people with MS, clinicians, and other stakeholders. This item pool will be used in a Delphi study to develop the scale, which will then be assessed for its psychometric properties. We will test whether respondents understand each item as it was intended to be understood, using cognitive interviews with people with MS. For more information please contact lead study researcher Heather Cogger-Ward ([email protected]).

Immune response to Epstein-Barr virus and cytomegalovirus in MS.

Funded by the Italian MS Society. It is very important to identify how the immune system responds to certain viral infections. MS is considered ‘immune-mediated’, because the immune system, normally involved in protection from infections, can react to certain viruses in a way that causes ‘collateral damage’ to the central nervous system. The most important infectious agent from this point of view is Epstein-Barr virus (EBV), a human herpesvirus. Without being infected by EBV, it is virtually impossible to develop MS. The stronger the antibody response to EBV when one is first infected, the higher the probability of developing MS in subsequent years. One of the most interesting strategies to prevent MS in the future is to develop a vaccine that prevents EBV infection or at least reduces the intensity of the immune response to it. In contrast to EBV, infection with cytomegalovirus (CMV), another human herpesvirus, is not associated with the development of MS, and may indeed be protective. We have been awarded a two-year research grant by the Italian MS Society to study the interaction of the immune responses to these two human herpesviruses, collaborating with two research groups in Rome, Italy. The aim is to better understand how the immune system responds to these viruses in people with MS, so that one day we can develop preventive interventions in people who are at high risk of developing the disease. For more information please contact Chief Investigator Dr. Bruno Gran ([email protected]).

Medication adherence in people with cognitive problems.

Funded by Health Education England (as part of the DClin Psy degree). Up to 70% of people with MS can have cognitive problems. We also know that many people with MS are on a complicated regimen of medications and treatments, and many times, people forget to take these treatments on time. Working with the UK MS Register, Sarah’s doctorate project will identify strategies related to disease-modifying treatment (DMT) adherence amongst people with MS with associated cognitive deficits, and whether the barriers and strategies related to DMT adherence differ between those who are adherent vs non-adherent. For more information please contact lead study researcher Sarah Thomason ([email protected]).

Preventing job loss in people with MS.

Funded by Joan Browne Legacy Funding. The average age of onset of MS is around 30 years of age when people are at the beginning of their professional career and seeking to live independently. Work is an important part of most people’s lives. After 10 years with MS, fewer than 50% remain at work and this figure decreases to 20% after 15 years. Blanca’s Ph.D. research aims to develop and test a job retention vocational rehabilitation intervention for people with MS. As part of her Ph.D., Blanca has reviewed various vocational rehabilitation programs offered for people with MS across the world and is adapting these for use in the UK context. She is currently evaluating this newly developed intervention as a series of case studies. For more information please contact lead study researcher Blanca De Dios Perez ([email protected]).