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Trial record 61 of 62 for:    Baricitinib

Evaluation of Pain Sensitization in Rheumatoid Arthritis: Analysis on a Cohort of Tofacitinib Treated Patients (TOPRA)

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ClinicalTrials.gov Identifier: NCT03815578
Recruitment Status : Recruiting
First Posted : January 24, 2019
Last Update Posted : July 2, 2019
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
University Hospital, Bordeaux

Brief Summary:

Persistent pain and chronic fatigue are very common complaints in rheumatoid arthritis (RA) patients, whatever the anti-inflammatory treatment response. Interestingly, pain remaining despite good clinical response was associated with high disability and low inflammation at baseline, suggesting a mechanism of pain independent of inflammation in these patients. Such patients, with discordantly high patient-reported DAS28 components, fatigue and mood disturbance might represent a subgroup of RA patients who have specific clinical needs, not resolved by classical conventional or biologic DMARDs. In this way, neuropathic pain and pain sensitization have been demonstrated in 20 to 30% of RA patients, neuropathic pain scores being associated with worsen disease activity scores. Thus, pain sensitization may contribute to amplification of pain in active RA, and should be responsible for persisting pain and fatigue even after inflammation has resolved.

Pain sensitization is associated with neuroplastic changes in sensory pathways at peripheral and central levels. Interestingly, major mediators responsible for this neuroplasticity operate via a JAK/STAT signaling pathway, which is specifically targeted by new RA treatments. New drug targeting JAK/STAT signalling pathway have been recently designed for RA treatment, based on the implication of this pathway on the signaling of various cytokines implicated in the pathophysiology of RA, such as IL-6, IL-12, IL-23 and IFNs. Two Jak-inhibitors have been put on the market: Tofacitinib and Baricitinib. In randomized clinical trials, Tofacitinib have shown a remarkable efficacy on pain and other patient reported outcomes, suggesting a specific effect or jak-inhibitors on pain control. Recent data suggest that Jak-inhibitors could have a direct effect on sensory neurons.


Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Other: Clinical examination Other: Pain assessment Other: blood sample Other: Patient Reported Outcomes Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 55 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Evaluation of Pain Sensitization in Rheumatoid Arthritis: Analysis on a Cohort of Tofacitinib Treated Patients
Actual Study Start Date : June 17, 2019
Estimated Primary Completion Date : January 17, 2021
Estimated Study Completion Date : January 17, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Rheumatoid Arthritis (RA) patients
RA according to the ACR/EULAR 2010 classification criteria
Other: Clinical examination
  • Number of painful joints,
  • Number of swollen joints,
  • Patient Global assessment VAS (0 - 100)
  • and Physician Global assessment VAS (0 - 100)

Other: Pain assessment
  • Pressure Pain Thresholds (PPTs),
  • Mechanical Temporal Summation (MTS)
  • and Diffuse Noxious Inhibitory Control (DNIC)

Other: blood sample
18 ml whole blood for ELISA analysis and miRNAs detection

Other: Patient Reported Outcomes
  • Health Assessment Questionnaire (HAQ),
  • Rheumatoid Arthritis Impact of Disease score (RAID),
  • Daily joint pain intensity VAS (0-100),
  • Hospital Anxiety and Depression scale
  • and Coping Strategy Questionnaire.




Primary Outcome Measures :
  1. Variation of the mean Pressure Pain Thresholds (PPTs) [ Time Frame: At 6 months from baseline ]

Secondary Outcome Measures :
  1. Variation of Mechanical Temporal Summation (MTS) [ Time Frame: At 1, 3 and 6 months from baseline ]
  2. Variation of Pressure Pain Thresholds (PPTs) [ Time Frame: At 1, 3 and 6 months from baseline ]
  3. Variation of Diffuse noxious inhibitory control (DNIC) values [ Time Frame: At 1, 3 and 6 months from baseline ]
  4. Variation of Daily joint pain intensity [ Time Frame: At 1, 3 and 6 months from baseline ]
    daily evaluation of the previous 24h pain on a numeric pain scale 0 to 100

  5. Disease activity evaluated by the Disease Activity Score on 28 joints (DAS28) [ Time Frame: At 1, 3 and 6 months from baseline ]
    which take into account the number of painful joints (on 28 joints), the number of swollen joints (on 28 joints), the patient global assessment of disease activity (between 0 and 100), and the erythrocyte sedimentation rate.

  6. Disease activity evaluated by the Simple Disease Activity Index (SDAI) [ Time Frame: At 1, 3 and 6 months from baseline ]
    which take into account the number of painful joints (on 28 joints), the number of swollen joints (on 28 joints), the patient global assessment of disease activity (between 0 and 100), the physician global assessment of disease activity (between 0 and 100), and the C-reactive protein level.

  7. Disease activity evaluated by the Clinical Disease Activity Index (SDAI) [ Time Frame: At 1, 3 and 6 months from baseline ]
    which take into account the number of painful joints (on 28 joints), the number of swollen joints (on 28 joints), the patient global assessment of disease activity (between 0 and 100), and the physician global assessment of disease activity (between 0 and 100).

  8. Health Assessment Questionnaire (HAQ) [ Time Frame: At 1, 3 and 6 months from baseline ]
  9. Rheumatoid Arthritis Impact of Disease score (RAID) [ Time Frame: At 1, 3 and 6 months from baseline ]
  10. Hospital Anxiety and Depression scale [ Time Frame: At 1, 3 and 6 months from baseline ]
    HAD scale aims at evaluating anxiety and depression symptoms with two separate scores (between 0 and 21) estimated grace to 14 items (7 for anxiety and 7 for depression) ranged between 0 and 3

  11. Coping Strategy Questionnaire: a 21-items self-report [ Time Frame: At 1, 3 and 6 months from baseline ]
  12. Levels of cytokines [ Time Frame: At 3 and 6 months from baseline ]
  13. Levels of neurotrophins [ Time Frame: At 3 and 6 months from baseline ]
  14. Levels of miR21, miR-124, miR-146a and miR-155 [ Time Frame: At 3 and 6 months from baseline ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients aged over 18 year-old ;
  • Diagnosis of RA according to the ACR/EULAR 2010 classification criteria ;
  • Active rheumatoid arthritis defined by a Disease Activity Score (DAS28) > 3.2 at inclusion ;
  • Patient eligible for tofacitinib treatment in agreement with European treatment labelling and French recommendation for RA treatment ;
  • Oral prednisone intake is allowed until 10 mg, stable for at least 1 week at study entry ;
  • Starting tofacitinib treatment for an active RA defined by a DAS28-ESR > 3.2 ;
  • Affiliated person or beneficiary of a social security scheme ;
  • Having signed an informed consent (at the latest on the day of inclusion and before any examination required by research).

Exclusion Criteria:

  • Diagnosis of a systemic autoimmune disease other than RA ;
  • Peripheral neuropathy ;
  • Centrally-acting pain medications use within 3 months of enrolment (amitriptyline, gabapentin, duloxetine), or during the study ;
  • Any opioid use within 1 month of enrolment or during the study ;
  • Corticosteroid treatment over 10 mg of prednisone or equivalent ;
  • Patient who present contraindications to tofacitinib treatment ;
  • Patient presenting with a history of active tuberculosis or chronic infectious disease with a need of regular use of antibiotic ;
  • Patients with active bacterial or viral infection, or presenting with an episode of infection that required treatment with antibiotics within 30 days prior to screening ;
  • Patient presenting with a history of lymphoma or leukaemia or other malignancy besides non-melanoma skin cancer within 5 years ;
  • Patient presenting with any uncontrolled medical condition ;
  • Pregnancy or breast-feeding ;
  • Patient unable to understand and follow recommendations or unable to perform self-evaluation ;
  • Patient who refuse to participate to the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03815578


Contacts
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Contact: Thierry SCHAEVERBEKE, Prof (0)556795556 ext +33 thierry.schaeverbeke@chu-bordeaux.fr
Contact: Thomas BARNETCHE, PhD thomas.barnetche@chu-bordeaux.fr

Locations
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France
CHU de Bordeaux - Service de rhumatologie Not yet recruiting
Bordeaux, France
Contact: Thierry SCHAEVERBEKE, Prof       thierry.schaeverbeke@chu-bordeaux.fr   
Contact: Thomas BARNETCHE, PhD       thomas.barnetche@chu-bordeaux.fr   
Principal Investigator: Thierry SCHAEVERBEKE, Prof         
CHU de Limoges - service de rhumatologie Recruiting
Limoges, France
Contact: Pascale VERGNE-SALLE, Prof       pascale.vergne-salle@chu-limoges.fr   
Principal Investigator: Pascale VERGNE-SALLE, Prof         
Sponsors and Collaborators
University Hospital, Bordeaux
Pfizer
Investigators
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Principal Investigator: Thierry SCHAEVERBEKE, Prof CHU - Bordeaux

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Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT03815578     History of Changes
Other Study ID Numbers: CHUBX 2017/39
First Posted: January 24, 2019    Key Record Dates
Last Update Posted: July 2, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Bordeaux:
pain sensitization
Tofacitinib
miRNA
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Tofacitinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action