Inhibition of Co-Stimulation in Rheumatoid Arthritis (ICoSRA)
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|ClinicalTrials.gov Identifier: NCT02652273|
Recruitment Status : Unknown
Verified January 2016 by NHS Greater Glasgow and Clyde.
Recruitment status was: Not yet recruiting
First Posted : January 11, 2016
Last Update Posted : January 12, 2016
|Condition or disease||Intervention/treatment||Phase|
|Arthritis, Rheumatoid||Drug: Abatacept||Phase 4|
Rheumatoid arthritis (RA) is a chronic inflammatory immune mediated arthritis which leads to pain, swelling and destruction of joints. RA affects more than 500,000 subjects in the United Kingdom (UK) and incurs significant health and economic cost. Most patients require potent immune suppressing drugs such as methotrexate, which help reduce pain and stiffness, and protect the joints against damage. However, many patients do not respond or are unable to tolerate methotrexate. In these patients, biologic drugs such as abatacept are used to try to control the arthritis.
Abatacept is designed to target and inhibit a specific molecule involved in "costimulation" of the inflammatory signal that is thought to be important in RA. While abatacept has been shown to be effective in trials and clinical practice, the exact mechanism of action of abatacept in RA has not been fully elucidated. Understanding these actions is likely to inform both the use of abatacept in RA and lead to increased understanding of inflammation in humans with implications for further therapies. This six month prospective open label study, therefore, aims to investigate the effects of inhibiting costimulation on a variety of important inflammatory cell types and processes in humans with RA.
25 participants with RA who have bad prognostic genetic markers (Anti-citrullinated protein antibodies (ACPA) and human leukocyte antigen (HLADR4) and who were scheduled to receive subcutaneous abatacept as part of their standard clinical treatment will be recruited. Consenting participants will followed for a total of 24 weeks during which time they will have additional venous blood and urine samples taken to investigate the effects of abatacept on their immune cells and system. The primary endpoint of the study is the characterisation of the immune response following costimulatory modulation in RA patients at 12 weeks. Secondary endpoints include change in immunological response and its association with clinical outcome measures up to 24 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Inhibition of Co-Stimulation in Rheumatoid Arthritis|
|Study Start Date :||January 2016|
|Estimated Primary Completion Date :||January 2019|
|Estimated Study Completion Date :||January 2019|
Abatacept 125mg administered via subcutaneous injection once a week for 24 weeks
- Immunological response [ Time Frame: Baseline and 12 weeks ]Change in T cell immune response to citrullinated peptides following costimulatory modulation
- Immunological response [ Time Frame: Baseline, 4, 12 and 24 weeks ]Change in immunological response from baseline, as measured by transcriptional profile of relevant cell subset
- Clinical response American College of Rheumatology (ACR) 20 [ Time Frame: Baseline and 24 weeks ]Change in ACR 20 from baseline
- Clinical response Disease Activity Score (DAS)28 [ Time Frame: Baseline and 24 weeks ]Change in DAS 28 from baseline
- T cell profile [ Time Frame: Baseline, 12 and 24 weeks ]Change in T cell subpopulation profile from baseline
- T cell response [ Time Frame: 24 weeks ]Antigen-specific T cell response to tetanus
- DC (CD11c+) phenotype [ Time Frame: 24 weeks ]Dendritic cell (DC) (CD11c+) phenotype as measured by major histocompatibility complex (MHC) II expression
- Biomarkers [ Time Frame: 24 weeks ]Preliminary identification of biomarkers of response using urinary metabol/proteomic analysis
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): NCT02652273
|Contact: Iain McInnes, Prof||+44 (0)141 330 firstname.lastname@example.org|
|Contact: Stefan Siebert, Dr||+44 (0) 141 330 email@example.com|
|NHS Greater Glasgow and Clyde|
|Glasgow, United Kingdom|
|Newcastle upon Tyne Hospitals NHS Foundation Trust|
|Newcastle upon Tyne, United Kingdom|
|Principal Investigator:||Iain McInnes, Prof||University of Glasgow|