Back to results

BARIcitinib Cognitive Emotional and Neural signaTuRE (BARICENTRE)

Primary Purpose

Rheumatoid Arthritis

Status

Recruiting

Phase

Phase 4

Locations

France

Study Type

Interventional

Intervention

Baricitinib Oral Tablet [Olumiant]

Placebo

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Active rheumatoid arthritis, Baricitinib treatment, Mood-improving effects, MRI

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

CHU Pitié SalpêtrièreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Baricitinib

Placebo

Arm Description

Patients receiving baricitinib 4mg/day for 7 days, then open label study until day 42 with all patients receiving baricitinib during 5 weeks. 20 patients in this arm will have a MRI at day 0 and day 8

Patients receiving placebo 4mg/day for 7 days, then open label study until day 42 with all patients receiving baricitinib during 5 weeks. 20 patients in this arm will have a MRI at day 0 and day 8

Outcomes

Primary Outcome Measures

Percentage of accurate responses in facial emotion recognition task

Percentage of accurate responses in facial emotion recognition task using Harmer's cognitive battery (based on Harmer & Cowen evaluation protocol)

Secondary Outcome Measures

DIfference in disease activity

DIfference in disease activity on DAS28 (disease activity score on 28 joints) - SDAI (Simplified Disease Activity Score)

Difference in function improvement

Difference in function improvement on HAQ (health assessment questionnaire)

Difference in pain

Difference in pain using Visual Analogic Scale (VAS) for pain

Difference in patient global assessment of the disease

Difference in VAS for patient global assessment of the disease

Number of accurate responses in facial emotion recognition task

The number of accurate responses in facial emotion recognition task using Harmer's cognitive battery (based on Harmer & Cowen evaluation protocol)

Difference in central and peripheral pain sensitization

Difference in central and peripheral pain sensitization using quantitative sensory testing

Difference in the results of psychometric questionnaire

Difference in the results of psychometric questionnaire using Hospital Anxiety and Depression Scale

Difference in blood-oxygen-level dependent (BOLD) signal activity in regions of interest (ROI) such as the subgenual anterior cingulate cortex (Sg-ACC) during a cyberball task

Main effect of group on social exclusion-related brain responses (e.g. actiavtion of the Sg_ACC ROI)

Difference in BOLD signal activity in pain-encoding brain regions

Main effect of group in pain-related brain responses

Differences in mood and pain assessments between patients with high or low expectations of the drug

Main effect of group on accurate responses during the facial emotion recognition task and pain assessment variables

Difference in BOLD signal activity in reward-learning related brain regions

Main effect of group reward-learning related brain responses (e.g. activation of the ventral striatum or vmPFC ROIs)

Full Information

NCT ID

NCT05238896

First Posted

January 4, 2022

Last Updated

August 22, 2022

Sponsor

Assistance Publique - Hôpitaux de Paris

1. Study Identification

Unique Protocol Identification Number

NCT05238896

Brief Title

BARIcitinib Cognitive Emotional and Neural signaTuRE

Acronym

BARICENTRE

Official Title

BARIcitinib Cognitive Emotional and Neural signaTuRE (BARICENTRE)

Study Type

Interventional

2. Study Status

Record Verification Date

February 2022

Overall Recruitment Status

Recruiting

Study Start Date

June 27, 2022 (Actual)

Primary Completion Date

August 2024 (Anticipated)

Study Completion Date

September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed 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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis

Keywords

Active rheumatoid arthritis, Baricitinib treatment, Mood-improving effects, MRI

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Baricitinib

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Patients receiving placebo 4mg/day for 7 days, then open label study until day 42 with all patients receiving baricitinib during 5 weeks. 20 patients in this arm will have a MRI at day 0 and day 8

Intervention Type

Drug

Intervention Name(s)

Baricitinib Oral Tablet [Olumiant]

Other Intervention Name(s)

Baricitinib

Intervention Description

Baricitinib 4 mg/d oral route for 42 days

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo, 4 mg/d, oral route for 7 days, then Baricitinib 4 mg/d oral route for 5 weeks

Primary Outcome Measure Information:

Title

Percentage of accurate responses in facial emotion recognition task

Description

Percentage of accurate responses in facial emotion recognition task using Harmer's cognitive battery (based on Harmer & Cowen evaluation protocol)

Time Frame

Day 1

Secondary Outcome Measure Information:

Title

DIfference in disease activity

Description

DIfference in disease activity on DAS28 (disease activity score on 28 joints) - SDAI (Simplified Disease Activity Score)

Time Frame

Day 0, 8 and 42

Title

Difference in function improvement

Description

Difference in function improvement on HAQ (health assessment questionnaire)

Time Frame

Day 0, 8 and 42

Title

Difference in pain

Description

Difference in pain using Visual Analogic Scale (VAS) for pain

Time Frame

Day 0, 8 and 42

Title

Difference in patient global assessment of the disease

Description

Difference in VAS for patient global assessment of the disease

Time Frame

Day 0, 8 and 42

Title

Number of accurate responses in facial emotion recognition task

Description

The number of accurate responses in facial emotion recognition task using Harmer's cognitive battery (based on Harmer & Cowen evaluation protocol)

Time Frame

Day 8

Title

Difference in central and peripheral pain sensitization

Description

Difference in central and peripheral pain sensitization using quantitative sensory testing

Time Frame

Day 0, 8 and 42

Title

Difference in the results of psychometric questionnaire

Description

Difference in the results of psychometric questionnaire using Hospital Anxiety and Depression Scale

Time Frame

Day 0, 8 and 42

Title

Difference in blood-oxygen-level dependent (BOLD) signal activity in regions of interest (ROI) such as the subgenual anterior cingulate cortex (Sg-ACC) during a cyberball task

Description

Main effect of group on social exclusion-related brain responses (e.g. actiavtion of the Sg_ACC ROI)

Time Frame

day 0 and day 8

Title

Difference in BOLD signal activity in pain-encoding brain regions

Description

Main effect of group in pain-related brain responses

Time Frame

day 0 and day 8

Title

Differences in mood and pain assessments between patients with high or low expectations of the drug

Description

Main effect of group on accurate responses during the facial emotion recognition task and pain assessment variables

Time Frame

Day 1,8 and 42

Title

Difference in BOLD signal activity in reward-learning related brain regions

Description

Main effect of group reward-learning related brain responses (e.g. activation of the ventral striatum or vmPFC ROIs)

Time Frame

day 0 and day 8

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Florian BAILLY, MD

Phone

0033 1 42 17 84 71

florian.bailly@aphp.fr

First Name & Middle Initial & Last Name or Official Title & Degree

Sarra POCHON

Phone

0033 1 42 16 75 74

sarra.pochon@aphp.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bruno FAUTREL, MD, PhD

Organizational Affiliation

Assistance Publique - Hôpitaux de Paris

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Florian BAILLY, MD

Organizational Affiliation

Assistance Publique - Hôpitaux de Paris

Official's Role

Study Chair

Facility Information:

Facility Name

CHU Pitié Salpêtrière

City

Paris

ZIP/Postal Code

75013

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Bruno Fautrel, Professor

Phone

0142177621

bruno.fautrel@psl.aphp.fr

First Name & Middle Initial & Last Name & Degree

Bruno Fautrel, Professor

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Data are available upon reasonable request. The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.

IPD Sharing Time Frame

Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor

IPD Sharing Access Criteria

Researchers who provide a methodological sound proposal.

Learn more about this trial

BARIcitinib Cognitive Emotional and Neural signaTuRE

We'll reach out to this number within 24 hrs