BARIcitinib Cognitive Emotional and Neural signaTuRE (BARICENTRE)

  • STATUS
    Recruiting
  • End date
    Sep 20, 2024
  • participants needed
    80
  • sponsor
    Assistance Publique - Hôpitaux de Paris
Updated on 4 October 2022
remission
adalimumab
baricitinib

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.

Description

Rheumatoid arthritis (RA) is a frequent and disabling disease, requiring early management to achieve clinical remission. Recently, baricitinib (jak1-jak2 inhibitor) has demonstrated its efficacy compared to placebo, 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. Inhibition of JAK pathway could have anti-inflammatory activity but also direct action on 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 Harmer's cognitive and emotional battery, This emotional aspect is a surrogate marker of future mood impact.

The primary outcome is the number of accurate responses in facial emotion recognition task at day 1 using Harmer's cognitive battery (based on Harmer & Cowen evaluation protocol at day 1).

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. At baseline (day 0), RA activity, mood symptoms, the number of accurate responses in facial emotion recognition task (Harmer's cognitive battery), clinical pain sensitization, will be assessed.3 follow-up research visits will be conducted at day 1, 8 and 42 (final visit) at the Pitié Salpêtrière hospital.The first intake of the Investigational medicinal product (IMP) (baricitinib or placebo) is at day 1. At day 1, the number of accurate responses in facial emotion recognition task and RA activity will be evaluated (2 to 4 hours after intake of baricitinib). At day 8 and 42, RA activity and flares, mood symptoms, the number of accurate responses in facial emotion recognition task (Harmer's cognitive battery), clinical pain sensitization, will be assessed. In each group (placebo vs Baricitinib), 20 patients will underwent a non-contrast MRI at day 0 and 8 (with evaluation of mood modification using BOLD signal during the different experimental conditions of the Cyberball task with comparison to baseline condition, and pain evaluation using fMRI-based neurological pain signature provided by Wager et al.) During the follow-up until day 42, patients will conduct questionnaires (day 15 and 29) at home about RA activity, pain (Patient pain VAS, Patient global assessment of the disease, Flare RA questionnaire) and psychometric questionnaire (Hospital Anxiety and Depression Scale)

Details
Condition Rheumatoid Arthritis
Treatment Placebo, Baricitinib Oral Tablet [Olumiant]
Clinical Study IdentifierNCT05238896
SponsorAssistance Publique - Hôpitaux de Paris
Last Modified on4 October 2022

Eligibility

Yes No Not Sure

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
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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note