Clad-B study
Research type
Research Study
Full title
Oral Cladribine B-cell study
IRAS ID
262436
Contact name
Sharmilee Gnanapavan
Contact email
Sponsor organisation
Joint Research Management Office Queen Mary, University of London and Barts Health NHS Trust.
Duration of Study in the UK
2 years, 11 months, 30 days
Research summary
Multiple sclerosis (MS) is a disease affecting the central nervous system. In MS the immune system mistakes the nerve cells myelin coating for a foreign body and creates an inflammatory attack against it. Many MS drugs act by targeting lymphocytes (B and T cells): however, which cell subsets may be implicated in MS, and the exact mechanisms by which they might contribute to pathogenesis, is unclear.
We propose to analyse the changes in peripheral blood lymphocyte subsets in both the depletion and repopulation phases after administration of the oral drug Cladribine.
MS is invariably associated with the presence of an oligoclonal IgG response (oligoclonal bands - OCBs) originating from plasma B cells in the cerebrospinal fluid. In a putative autoimmune disease such as MS these OCBs may be targeting self-antigens and may therefore be responsible for driving progressive MS pathology. Cladribine penetrates the blood-brain barrier, and this suggests it may also target intrathecal (cerebrospinal fluid) plasma B cells.
We therefore propose to analyse the effect of Cladribine on OCBs, as well as other markers of inflammation and neuronal damage.
Patients with MS who are being treated with oral Cladribine at Barts Health NHS Trust will be approached to participate in this study and asked to donate bloods, urine and cerebrospinal fluid samples over a period of two years.Lay Summary of Results
Recent research highlights the effectiveness of therapies targeting B cells in managing multiple sclerosis (MS), particularly in reducing disease activity. B cells play a crucial role in the development of MS. The CladB study focused on understanding how the immune system changes over 96 weeks when treated with Cladribine tablets (CladT) in people with relapsing-remitting MS (RRMS).
The study involved 10 participants (3 men and 7 women) who provided blood samples at multiple intervals, ranging from the first day of treatment to every few weeks over nearly two years. These results were compared with a historical group treated with another MS therapy called alemtuzumab. The study also collected spinal fluid samples to assess various immune markers, alongside regular clinical check-ups and brain scans.
Results showed that CladT treatment mainly reduced memory B cells, which are crucial in MS. Unlike alemtuzumab, which rapidly reduced both T and B cells, CladT specifically targeted memory B cells. Key findings included:
-A decrease in the кFLC index (a measure of antibody production) from 164.5 to 64.4 over 96 weeks.
-A reduction in the IgG index (another marker of immune activity) from 1.1 at the start to 0.8 after 96 weeks.
-Lower levels of the inflammation marker CXCL-13 in the spinal fluid, dropping from 88.6 to 19.1 pg/mL by the end of the study.
-A reduction in NfL levels (a marker of nerve damage) in the spinal fluid after 48 weeks.Overall, CladT showed a long-term impact on reducing specific immune cells and markers related to inflammation and nerve damage in RRMS, suggesting it can effectively manage MS progression by targeting memory B cells.
Has the registry been updated to include summary results?: No
If yes - please enter the URL to summary results:
If no – why not?: Pending
Did you follow your dissemination plan submitted in the IRAS application form (Q A51)?: Yes
If yes, describe or provide URLs to disseminated materials: Published in MedRxiv and Clinical Immunology journal
If pending, date when dissemination is expected:
If no, explain why you didn't follow it:
Have participants been informed of the results of the study?: Yes
If yes, describe and/or provide URLs to materials shared and how they were shared: Participants were emailed a copy of the article.
If pending, date when feedback is expected:
If no, explain why they haven't:
Have you enabled sharing of study data with others?: Yes
If yes, describe or provide URLs to how it has been shared: In the publication it states upon request
If no, explain why sharing hasn't been enabled:
Have you enabled sharing of tissue samples and associated data with others?: Yes
If yes, describe or provide a URL: In the publication it states upon request.
If no, explain why:
Submitted on: 10/11/2024REC name
London - Stanmore Research Ethics Committee
REC reference
19/LO/0789
Date of REC Opinion
19 Jun 2019
REC opinion
Further Information Favourable Opinion