| CTRI Number |
CTRI/2025/06/088551 [Registered on: 10/06/2025] Trial Registered Prospectively |
| Last Modified On: |
08/06/2025 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Observational |
|
Type of Study
|
Follow Up Study |
| Study Design |
Other |
|
Public Title of Study
|
Study to evaluate the role of blood cells in tracking disease activity and treatment response in people with Rheumatoid Arthritis |
|
Scientific Title of Study
|
Evaluating the Systemic Immune-Inflammation Index as a marker for disease activity and treatment response in Rheumatoid Arthritis |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Shreya Menon |
| Designation |
Junior Resident |
| Affiliation |
Kasturba Medical College, Manipal |
| Address |
Department of General Medicine, Kasturba Medical College, Manipal
Udupi
KARNATAKA
576104
India |
| Phone |
9811491530 |
| Fax |
|
| Email |
shreiyamenon@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Chandrashekar UK |
| Designation |
Professor and Unit Head |
| Affiliation |
Kasturba Medical College, Manipal |
| Address |
Department of General Medicine, Kasturba Medical College, Manipal
Udupi
KARNATAKA
576104
India |
| Phone |
9845163448 |
| Fax |
|
| Email |
shekar.uk@manipal.edu |
|
Details of Contact Person
Public Query
|
| Name |
Dr Chandrashekar UK |
| Designation |
Professor and Unit Head |
| Affiliation |
Kasturba Medical College, Manipal |
| Address |
Department of General Medicine, Kasturba Medical College, Manipal
Udupi
KARNATAKA
576104
India |
| Phone |
9845163448 |
| Fax |
|
| Email |
shekar.uk@manipal.edu |
|
|
Source of Monetary or Material Support
|
| Kasturba Medical College, Manipal, Karnataka, India,
Pincode - 576104 |
|
|
Primary Sponsor
|
| Name |
Dr Shreya Menon |
| Address |
Department of General Medicine, Kasturba Medical College, Manipal, Karnataka, India, Pincode 576104 |
| Type of Sponsor |
Other [SELF] |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Shreya Menon |
Kasturba Medical College, Manipal |
Department of General Medicine, Kasturba Medical College, Manipal
Udupi
KARNATAKA |
9811491530
shreiyamenon@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Kasturba Medical College and Kasturba Hospital Institutional Ethics Committee - 2 (Student Research) |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: M05||Rheumatoid arthritis with rheumatoid factor, (2) ICD-10 Condition: M06||Other rheumatoid arthritis, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Nil |
Nil |
| Comparator Agent |
Nil |
Nil |
| Intervention |
Nil |
Nil |
| Intervention |
Nil |
Nil |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
80.00 Year(s) |
| Gender |
Both |
| Details |
1. Patients diagnosed with Rheumatoid Arthritis (RA) based on the 2010 ACR/EULAR classification criteria, either as inpatients or outpatients, will be recruited for the study.
2. Age greater than or equal to 18 years.
3. Either treatment naive or patients who have not been adequately treated with csDMARDs (conventional synthetic Disease Modifying Antirheumatic Drugs) and tsDMARDs (targeted synthetic Disease Modifying Antirheumatic Drugs), as well as those who have discontinued treatment or have poor adherence.
4. Willing to participate and provide informed consent. |
|
| ExclusionCriteria |
| Details |
1. Patients who have received adequate dose of csDMARDs and tsDMARDs in the last 1 month.
2. Patients on steroids (10 mg/day of prednisolone or equivalent) in the past 4 weeks before enrollment.
3. Patients with iron deficiency anemia or thrombocytopenia
4. Patients with active infections such as tuberculosis or chronic viral hepatitis
5. Patients with concurrent autoimmune or inflammatory diseases such as lupus, psoriatic arthritis or inflammatory bowel disease.
6. Patients with a history of malignancy.
7. Pregnant or breast feeding women
8. Patients with severe renal or hepatic impairment (eGFR less than 30ml per minute per 1.73 metre square or liver enzymes greater than 3 times the upper limit of normal) |
|
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Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Not Applicable |
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Primary Outcome
|
| Outcome |
TimePoints |
| To evaluate the Systemic Immune-Inflammation Index (SII) as a biomarker for disease activity and treatment response in newly diagnosed Rheumatoid Arthritis (RA) patients over a 12 month period |
At 3 months, 6 months and 12 months |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| To assess the correlation between SII and established disease activity indices - Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI), in newly diagnosed RA patients |
At 3 months, 6 months and 12 months |
| To determine the ability of SII to predict changes in disease activity following initiation of therapy over a 12 month follow up. |
At 3 months, 6 months and 12 months |
|
|
Target Sample Size
|
Total Sample Size="95"
Sample Size from India="95"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
20/06/2025 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="6"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
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Brief Summary
|
Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, leading to progressive joint destruction, functional impairment and increased morbidity. Effective disease management relies on early diagnosis and prompt initiation of disease modifying anti-rheumatic drugs (DMARDS) to control inflammation and prevent irreversible joint damage. Conventional markers of inflammation, such as C- Reactive Protein (CRP) and erythrocyte sedimentation rate (ESR) are frequently used to assess disease activity. However these markers can be affected by comorbidities & infections, highlighting the need for more reliable inflammatory markers for disease monitoring. The Systemic Immune- Inflammation Index (SII) is a new biomarker that combines platelet, neutrophil and lymphocyte counts to reflect systemic inflammation. The SII is calculated as (platelet count X neutrophil count ) / lymphocyte count. This ratio provides a measure of the balance between immune activation and inflammation, making it a valuable marker for assessing systemic inflammatory status. In RA, systemic inflammation plays a crucial role in disease pathogenesis, and the SII has been proposed as a potential marker for disease activity and treatment response. A recent study by Liu et al.(2023) using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 found a significant association between SII and RA, suggesting that higher SII values correlate with increased disease severity. Despite these promising findings, there remains a gap in understanding the role of SII in newly diagnosed RA patients, particularly in predicting treatment response over time. Established disease activity indices such as Clinical Disease Activity Index ( CDAI) and Simplified Disease Activity Index (SDAI) provide comprehensive assessments of RA severity. If SII proves to be a reliable and easily accessible biomarker, it could help identify patients with high disease activity early and improve treatment decisions. The study by Liu et al. (2023) analyzed the association between the SII and the presence of RA in a general population. Their study assessed SII at a single time point and determined its correlation with RA diagnosis (cross sectional design). This approach helped establish that SII is significantly associated with RA but did not evaluate disease activity and treatment response. In contrast, the present study is a prospective longitudinal study aimed to evaluate SII as a biomarker for disease activity and treatment response over 12 months in newly diagnosed RA patients. Instead of assessing a general population, present study will focus specifically on patients at the time of diagnosis and track their response to treatment over time using established disease activity indices (CDAI, SDAI). This will allow us to determine whether SII can predict changes in disease activity following therapy, something that Liu et al.(2023) did not explore.
The hypothesis for this study is that the Systemic Immune-Inflammation Index (SII) is associated with disease activity indices (CDAI, SDAI) in newly diagnosed RA patients. Higher baseline SII predict greater disease activity and poorer treatment response over 12 months. A decline in SII following treatment initiation is expected to correlate with clinical improvement in RA disease activity indices. This study will address a key gap in the literature by evaluating whether SII can serve as a useful marker for disease monitoring, distinguishing it from previous cross-sectional studies like Liu et al. (2023).
Aim of the Study To evaluate the Systemic Immune-Inflammation Index (SII) as a biomarker for disease activity and treatment response in newly diagnosed rheumatoid arthritis (RA) patients over a 12-month period.
Objectives 1.To assess the correlation between SII and established disease activity indices (CDAI, SDAI) in newly diagnosed RA patients. 2. To determine the ability of SII to predict changes in disease activity following initiation of therapy over a 12-month follow-up. Methodology Patients will be selected based on the inclusion & exclusion criteria and will be recruited into the study after obtaining written informed consent. At baseline, blood samples will be collected to assess various hematological and biochemical parameters. The Systemic Immune-Inflammation Index (SII) will be calculated using the formula: (Platelet count × Neutrophil count) / Lymphocyte count. A complete blood count (CBC) will be performed, including WBC count, neutrophil count, lymphocyte count, platelet count, and hemoglobin levels. Baseline liver function tests (LFTs) and renal function tests (RFTs) will be performed and documented. The same blood sample will be used for measuring inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Autoantibody testing, including rheumatoid factor (RF) and anti-citrullinated peptide antibody (Anti-CCP) will be performed. If anaemia or thrombocytopenia is detected, additional tests will be performed as part of the standard of care: serum Iron, Total Iron Binding Capacity (TIBC) for anaemia, and Vitamin B12 and folate levels for thrombocytopenia. To assess disease activity, validated clinical scoring systems, such as DAS28, CDAI, and SDAI will be used. The Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and Disease Activity Score using 28 joints (DAS28) will be recorded at the baseline. The Patient Global Assessment (PGA) and Physician Global Assessment will also be documented at the baseline.
At follow-up visits (3, 6, and 12 months), blood samples will be collected to reassess the Systemic Immune-Inflammation Index (SII). Complete blood count (CBC), including WBC count, neutrophil count, lymphocyte count, platelet count, and hemoglobin levels will be performed, along with measurements of CRP. Liver function tests (LFTs) and renal function tests (RFTs) will also be conducted. Disease activity scores, including the Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI) will be reassessed to evaluate treatment response. The predictive ability of baseline SII for treatment response over 12 months will be analyzed, and changes in SII over time will be correlated with clinical improvement. Adverse effects of therapy and medication adherence will be monitored throughout the study. Patients diagnosed with rheumatoid arthritis (RA) as inpatients or outpatients, after initiating DMARDs or biologics, will be followed up as outpatients for clinical outcomes. The primary outcome will be assessed based on changes in disease activity scores, including the Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI). The secondary outcome will be evaluated by improvements in inflammatory markers such as the Systemic Immune-Inflammation Index (SII), and C-reactive protein (CRP), as well as changes in medication adherence.
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