Gene Expression Profiling in PBMCs as a Tool for Prediction of Infliximab Responsiveness in Rheumatoid Arthritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Rouen
ClinicalTrials.gov Identifier:
NCT00213564
First received: September 13, 2005
Last updated: June 25, 2013
Last verified: June 2013
  Purpose

The objective of the study is to identify and validate predictive markers of infliximab responsiveness in RA patients by 2 approaches: i) measuring biochemical, immunological and bone markers in sera because of their involvement in pathogenic mechanisms; ii) identifying gene-expression signatures in PBMCs by the transcriptomic analysis.

Patients with active RA (ACR criteria) were given i.v. 3 mg/kg infliximab associated with metotrexate at weeks 0, 2, 6, and every 8th week. Infliximab efficacy was evaluated at week 14, using the EULAR response criteria.

  1. Just before the starting of infliximab treatment, the following parameters were measured in the sera: i) immunological tests: rheumatoid factor (IgA, IgG, IgM), anti-CCP, autoAb recognizing the 27 C-terminal fragment (ACAST-C27) and domain I (ACAST-DI) of calpastatin, anti-G6PI, anti a-enolase, anti-keratin and anti-perinuclear factor; ii) biochemical markers: CRP, MMP-1, MMP-3, TIMP-1, TIMP-2; markers of bone resorption: pyridinolin, deoxypyridinolin, osteoprotegerin, sRANKL, COMP. The predictive value of each parameter for a response/non-response to infliximab was analysed using Fischer's exact, Mann-Whitney and Chi2 tests.
  2. A blood sample was collected just before the onset of infliximab treatment and total RNAs were extracted from the peripheral blood mononuclear cells. The [33P] radiolabeled mRNAs were hybridized (duplicate or triplicate) over a set of 10.000 human cDNA probes spotted at a high density on nylon membranes. Data were normalized and filtered to allow the comparison between RNA samples. Statistical analyses were performed with the R software and hierarchical clustering was performed with the Cluster and Tree View softwares.

Condition Intervention Phase
Rheumatoid Arthritis
Drug: response to infliximab associated with methotrexate
Phase 4

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Gene Expression Profiling in PBMCs as a Tool for Prediction of Infliximab Responsiveness in Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by University Hospital, Rouen:

Estimated Enrollment: 40
Study Start Date: April 2003
Study Completion Date: December 2005
Primary Completion Date: May 2004 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Is age 18 years old or older Satisfies the 1987 American College of Rheumatology revised criteria for Rheumatoid arthritis Has active disease at the time of randomization as indicated by a DAS28> 5.1 Has a disease at least refractory to DMARDs whose methotrexate or leflunomide Is capable of understanding and signing an informed consent form Agrees to use a medically accepted form of contraception during the study

Exclusion Criteria:

  • Is pregnant or breast-feeding or without Has significant concurrent medical diseases including cancer or a history of cancer within 5 years of entering the study, uncompensated congestive heart failure, significant active infection or any underlying diseases that could predispose subjects to infections (whose tuberculosis) Has allergy to infliximab
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00213564

Locations
France
CHU de Rouen - Hôpitaux de Rouen
Rouen, France, 76031
Sponsors and Collaborators
University Hospital, Rouen
Investigators
Principal Investigator: Xavier Le Loët Rouen university Hospital
  More Information

No publications provided

Responsible Party: University Hospital, Rouen
ClinicalTrials.gov Identifier: NCT00213564     History of Changes
Other Study ID Numbers: 2002/061/HP
Study First Received: September 13, 2005
Last Updated: June 25, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Infliximab
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Gastrointestinal Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 24, 2014