Identifying genetic determinants of outcome in multiple sclerosis

ISRCTN ISRCTN41688895
DOI https://doi.org/10.1186/ISRCTN41688895
IRAS number 324856
Secondary identifying numbers A096498, IRAS 324856
Submission date
22/04/2023
Registration date
04/05/2023
Last edited
19/06/2025
Recruitment status
Not yet recruiting
Overall study status
Ongoing
Condition category
Nervous System Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Background and study aims
Multiple sclerosis (MS) is what scientists call an “autoimmune” disease. In such diseases the immune system is faulty and mistakenly attacks part of the body. In MS, this faulty attack is directed against the central nervous system (CNS); that is against the brain and the spinal cord. The damage caused by MS results in increasingly severe neurological disability that is known as disease “progression”. The rate at which this irreversible damage develops varies greatly between patients. Some become markedly disabled very quickly, while others develop little or no disability even after years. This study will examine the DNA code from people with MS in order to identify genetic factors that influence how quickly progression develops in the disease. That is, to identify changes in the DNA sequence that influence the outcome of the disease.

Who can participate?
People with MS who have had their disability recorded at least once using a clinical assessment called the Extended Disability Status Scale (EDSS). The EDSS is frequently measured in MS research studies and is now also often measured as part of routine clinical care.

What does the study involve?
The study involves the genetic analysis of DNA donated by participants. The DNA will be extracted either from venous blood or saliva collected from participants. The analysis of the DNA will be undertaken in the laboratory. The genetic data emerging from the laboratory analysis will be correlated with the demographic and clinical details collected about the participants.

What are the possible benefits and risks of participating?
This is an observational study in which the only intervention is the collection of venous blood. This collection will be undertaken by professional appropriately trained staff. The collection of venous blood is a routine procedure with no meaningful risk. The study will also involve the sharing of data about participants between the researchers involved in the study. All data sharing in the study will be undertaken in accordance with best practice and legal requirements such as GDPR. There are no benefits to participants from taking part in the study other than the knowledge that they are helping to bring effective treatments closer for future generations of patients.

Where is the study run from?
The University of Cambridge (UK)

When is the study starting and how long is it expected to run for?
September 2022 to September 2030

Who is funding the study?
Funding for the study is not yet confirmed

Who is the main contact?
Prof. Stephen Sawcer, sjs1016@cam.ac.uk

Contact information

Prof Stephen Sawcer
Principal Investigator

Department of Clinical Neurosciences
Addenbrookes Hospital, BOX165
Hills Road
Cambridge
CB2 0QQ
United Kingdom

ORCiD logoORCID ID 0000-0001-7685-0974
Phone +44 (0)1223 762040
Email sjs1016@cam.ac.uk
Prof Stephen Sawcer
Scientific

Department of Clinical Neurosciences
Addenbrookes Hospital, BOX165
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Phone +44 (0)1223 762040
Email sjs1016@cam.ac.uk
Prof Stephen Sawcer
Public

Department of Clinical Neurosciences
Addenbrookes Hospital, BOX165
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Phone +44 (0)1223 762040
Email sjs1016@cam.ac.uk

Study information

Study designGenome wide association screen
Primary study designObservational
Secondary study designEpidemiological study
Study setting(s)Laboratory
Study typeOther
Participant information sheet Not available in web format, please use the contact details to request a participant information sheet
Scientific titleProgression in Multiple Sclerosis
Study acronymPIMS
Study objectivesThe primary aim of this study is to identify genetic variants influencing the clinical course of multiple sclerosis
Ethics approval(s)Not provided at time of registration
Health condition(s) or problem(s) studiedMultiple sclerosis
InterventionThe researchers will undertake array-based genome-wide genotyping in DNA extracted from patients' venous blood or saliva
Intervention typeGenetic
Primary outcome measureDisability measured using the Extended Disability Status Scale (EDSS) and age-corrected to generate the Age-Related Multiple Sclerosis Severity (ARMSS) Score. All available measures of the ARMSS will be considered in the analysis as observed at any timepoint in the disease course.
Secondary outcome measuresTIme to event measures including time to EDSS 6.0 and time to confirmed disability worsening. These variables will be assessed in the sub-group of patients with EDSS measured at multiple timepoints.
Overall study start date01/09/2022
Completion date30/09/2030

Eligibility

Participant type(s)Patient
Age groupAdult
SexBoth
Target number of participants10000
Key inclusion criteria1. A locally confirmed diagnosis of multiple sclerosis
2. At least one measure of Extended Disability Severity Score (EDSS)
3. Able to give valid informed consent
Key exclusion criteria1. Patients with Radiologically or Clinically Isolated Syndrome (RIS or CIS)
2. Comorbidities causing significant disability likely to have confounded the reliability of the EDSS
3. Inclusion in the discovery cohort of the recently completed first progression GWAS
Date of first enrolment01/10/2025
Date of final enrolment30/09/2028

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Addenbrookes
Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Sponsor information

Cambridge University Hospitals NHS Foundation Trust
Hospital/treatment centre

Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom

Phone +44 (0)1223 348490
Email cuh.research@nhs.net
Website http://www.cuh.org.uk/
ROR logo "ROR" https://ror.org/04v54gj93

Funders

Funder type

Other

Not yet confirmed

No information available

Results and Publications

Intention to publish date01/06/2026
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryStored in publicly available repository
Publication and dissemination planPlanned publication in a high-impact peer-reviewed journal
IPD sharing planIt is the researchers' intention to store the data generated in this study (demographic, clinical and genetic) in a genomics data repository such as the European Genome-Phenome Archive (EGA, https://ega-archive.org/). Anonymised data will be available when the results of the study are published by application to the Data Access Committee (DAC) via the repository. All participants will consent to data sharing with bona fide third-party researchers undertaking appropriate biomedical research.

Editorial Notes

19/06/2025: The following changes were made to the trial record:
1. The recruitment start date was changed from 01/06/2023 to 01/10/2025.
2. The recruitment end date was changed from 01/06/2025 to 30/09/2028.
3. The overall end date was changed from 01/06/2025 to 30/09/2030.
4. The plain English summary was updated to reflect these changes.
24/04/2023: Trial's existence confirmed by the Cambridge University Hospitals NHS Foundation Trust.