BARIcitinib Cognitive Emotional and Neural signaTuRE

• Status: Not yet recruiting
• Trial end date: 2024-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Rheumatoid arthritis (RA) is a frequent and disabling disease, requiring early management to achieve clinical remission. Recently, baricitinib (jak1-jak2 inhibitor) has been shown to as an efficient treatment in placebo-controlled trials, and compared to the reference treatment with TNF inhibitor (adalimumab). Its efficacy has been reported on the inflammatory parameters, but more importantly on patient-reported outcomes. Baricitinib is thought to have anti-inflammatory effects, via its inhibition of the JAK pathway. Importantly, it has also been suggested to affect mood and pain.

Hypotheses: Inhibition of JAK Kinase pathway in patients with RA will improve emotional and cognitive processing involved in mood disorders and decrease pain sensitization.

The primary objective of this study is to evaluate early emotional impact of the JAK 1/2 inhibitor Baricitinib assessed by a facial emotion recognition task. This precocious effect on emotion processing is a surrogate marker of clinical imporvement in mood.

Phase 4 study, Double-blind randomized control study with patients receiving placebo or baricitinib for 7 days, then open label study until day 42 with all patients receiving baricitinib during 5 weeks.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Criteria

Inclusion Criteria:

• Patients aged between 18 and 75 years

• Diagnosis of RA according to the ACR/EULAR 2010 classification criteria

• Active rheumatoid arthritis at inclusion (defined by a Disease Activity Score (DAS28) > 3.2)

• Patient eligible for baricitinib treatment in agreement with European label and French recommendations for RA treatment with dosage of 4mg (patients with 2mg dosage will not be included to ensure patient homogeneity)

• Informed and signed consent

• Affiliation to a french social security system (beneficiary or legal)

• For child-bearing aged women, efficient contraception

Exclusion Criteria:

• Patient under tutorship or guardianship, and incapable to give informed consent

• Diagnosis of a systemic autoimmune disease other than RA

• Treatment not allowed:

• DMARDS other than Methotrexate or Leflunomide or Hydroxychloroquine or Salazopyrine.

• Psychotropic treatments (antidepressive drugs, benzodiazepine, mood stabilizer) during the study or the month prior the study that could change the mood evaluation.

• Laboratory exclusions: o Total white blood cell count (WBC) less than 3 x 109 cells/L o Absolute lymphocyte count (ALC) less than 0.5 x 109 cells/L o Absolute neutrophil count (ANC) less than 1 x 109 cells/L o Hemoglobin less than 8.0 g/dl o eGFR < 60 mL/min/1.73 m² based on the most recent serum creatinine (Cockroft-Gault method) o ALT or AST > 5 times upper limit of normal o Any abnormality on screening laboratory tests that, in the opinion of the investigator, could represent a risk when participating in this protocol

• Any contraindications to baricitinib treatment or to Non-contrast MRI exam

• Hypersensitivity to the active substance or to any of the excipients

• History of active tuberculosis without treatment or chronic infectious diseasewith a need of regular use of antibiotic

• Active or prior bacterial or viral infection that required treatment with antibiotics within 30 days prior to screening

• History of lymphoma or leukemia or other malignancy besides non-melanoma skin cancer within 5 years

• Uncontrolled medical condition or planned major surgery during the study

• Pregnancy or breast-feeding

• Claustrophobia

• Patient unable to understand and follow recommendations or unable to perform self-evaluation

• Participation in another interventional study or being in the exclusion period at the end of a previous study.

• Patients with current suicidal intents or behaviors, Past or present depression or anxiety will be neither a criterion for inclusion nor a criterion for non-inclusion but will be collected in case report form.