Multiple Sclerosis, Relapsing-Remitting
Conditions
Keywords
multiple sclerosis, aHSCT, Autologous haematopoetic stem cell transplantation
Brief summary
The underlying disease mechanisms which occur in patients with immune mediation neurological diseases, such as Multiple Sclerosis (MS), are incompletely understood. For such patients, autologous haematopoietic stem cell transplantation (aHSCT) has been increasingly used as a highly successful one-off treatment for some patients. This treatment aims to delete the faulty immune system with a course of chemotherapy and then 'reboot' the immune system using a patients' own stem cells (a cell with the unique ability of being a building block to create many different cells in the body) to stop further damage. Over the last 20 years more than 1800 patients with MS have been treated in Europe with high levels of success. It may be more successful than disease modifying treatment but unfortunately, a small portion of people do not respond to this treatment optimally and continue to accumulate disability. There is a risk of side effects, restricted largely to the time of treatment, which necessitates the need to ensure appropriate patients are treated. Whilst aHSCT is a very effective therapy, it is still in its early phase of development, is not in widespread use, and there is incomplete knowledge regarding how it works and importantly, why it does not work in some patients, and how to monitor response to treatment. Unfortunately, there is no way of detecting which patients will, and will not, benefit from the different treatments available or a way of monitoring the immune system to ensure further treatment is provided before irreversible damage occurs. This study will investigate the immune system which is found in the fluid surrounding the brain and spinal cord, blood and stool of patients undergoing aHSCT and compare it to those receiving disease modifying treatment. This study will therefore further the understanding of biomarkers of aHSCT to develop an awareness of how it can be refined, may improve monitoring of patients following treatment and permit the development of markers which can predict potential treatment success or failure before patients are exposed to the risks.
Interventions
None listed
Sponsors
Sheffield Hospitals Charity
Nottingham Trent University
University of Sheffield
Sheffield Teaching Hospitals NHS Foundation Trust
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of a immune mediated neurological disease according to disease specific criteria (active treatment arm) or diagnosis of relapsing remitting multiple sclerosis (control arm). 2. Treatment with autologous haematopoetic stem cell transplantation (active treatment arm) or high efficacy disease modifying treatment (control arm). 3. Willing to provide biological samples for analysis and undergo clinical assessments for the duration of follow up. 4. Able to understand English and provide informed consent.
Exclusion criteria
1\. Inability to provide informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quantitatively and qualitatively characterise the immune profile of the stem cells, blood, cerebrospinal fluid (CSF) and the microbiome pre and post treatment. | 24 months | Phenotype profiling of stem cells, cells in blood and CSF using multi-parameter flow cytometry. Profile the gut microbiome using 16S rRNA sequencing and flow cytometric analysis. |
| Perform single cell RNA sequencing (scRNA-Seq) on paired CSF and blood pre and post treatment. | 24 months | Profiling of T cell receptor and B cell receptor repertoire diversity and clonality |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate immunological disease response and the duration of response to aHSCT according to low contrast visual acuity (LCLA) | 24 months | LCLA to be observed longitudinally following treatment. |
| Evaluate immunological disease response and the duration of response to aHSCT according to multiple sclerosis functional composite score (MSFC) | 24 months | MSFC to be observed longitudinally following treatment. |
| Characterisation of the regeneration of mucosal cell immunity and the reconstitution of pathogen specific immunity following aHSCT by scRNA-Seq on nasopharyngeal swabs and mucosal strips. | 24 months | Assess immune response in treated patients post vaccination. |
| Evaluate immunological disease response and the duration of response to aHSCT according to symbol digit modality test (SDMT) | 24 months | SDMT to be observed longitudinally following treatment. |
| Evaluate immunological disease response and the duration of response to aHSCT according to Karnofsky performance status | 24 months | Karnofsky performance status to be observed longitudinally following treatment. |
| Evaluate immunological disease response and the duration of response to aHSCT according to short form 36 (SF-36) | 24 months | SF-36 to be observed longitudinally following treatment. |
| Evaluate immunological disease response and the duration of response to aHSCT according to expanded disability status scale score (EDSS) | 24 months | EDSS to be observed longitudinally following treatment. |
Countries
United Kingdom
Contacts
Primary ContactGavin Brittain, MBBS, MRCP
Outcome results
None listed