A New Mode of Action of Anti-TNF, Reverse Signaling, in Rheumatoid Arthritis

Study Overview
=================
Brief Summary
-----------------
Blood test in Rheumatoid Arthritis (RA) patients with good response to anti-Tumor Necrosis Factor (anti-TNF) and in patients with moderate or non-response will be done in the month following the evaluation of clinical response to therapy. Isolation of mononuclear cells and purification of monocyte by negative selection. Cell culture of monocyte in presence or not of anti-TNF for 24 hours and analyze of CD36 (cluster of differentiation antigen 36) expression (principal outcome). For secondary outcomes analyze monocyte phenotype, NRF2 nuclear translocation, and clinical data of patients.

Official Title
-----------------
Pilot Study Investigating a New Mode of Action of Anti-TNF, Reverse Signaling, in Rheumatoid Arthritis

Conditions
-----------------
Rheumatoid Arthritis

Intervention / Treatment
-----------------
* Diagnostic Test: Blood test


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: RA defined according to the American College of Rheumatology (ACR) 2010 criteria, treated by anti-TNF + methotrexate, good responders in in one arm, and moderate or non-responders in the other arm according to EULAR (European Ligue Against Rheumatism) response criteria after three months of treatment Exclusion Criteria: contra-indication to anti-TNF corticosteroid more than 10mg by a day equivalent prednisone, modification of DMARD (disease-modifying antirheumatic drugs) in the last three months comprehension trouble Factors modifying CD36 -cluster of differentiation antigen 36- expression as diabetes mellitus, kidney disease, HIV

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>patients with good response to anti-TNF had a blood test | Diagnostic Test: Blood test<br> <br> |
| Experimental: Group 2<br>patients with moderate or non-response to anti-TNF had a blood test | Diagnostic Test: Blood test<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD36 expression | Percentage of increase of CD36 (cluster of differentiation 36) expression induced by anti-TNF ex vivo after 24h of cell culture in two groups of human monocytes: monocytes providing of RA patients good responder to anti-TNF in one hand, and moderate or non-responder in the other hand. | Day 0 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Monocytes | Phenotype of freshly isolated monocytes before cell-culture | Day 0 | 
| Nuclear translocation of NRF2 | Nuclear translocation of Nuclear factor (erythroid-derived 2)-like 2 (NRF2) induced by anti-TNF ex vivo | Day 0 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Reverse Signaling, Anti-TNF