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

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Clinical examination
Pain assessment
blood sample
Patient Reported Outcomes
Sponsored by
University Hospital, Bordeaux
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Rheumatoid Arthritis focused on measuring pain sensitization, Tofacitinib, miRNA

Eligibility Criteria

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

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.

Sites / Locations

  • CHU de Bordeaux - Service de rhumatologie
  • CHU de Limoges - service de rhumatologie

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Rheumatoid Arthritis (RA) patients

Arm Description

RA according to the ACR/EULAR 2010 classification criteria

Outcomes

Primary Outcome Measures

Variation of the mean Pressure Pain Thresholds (PPTs)

Secondary Outcome Measures

Variation of Mechanical Temporal Summation (MTS)
Variation of Pressure Pain Thresholds (PPTs)
Variation of Diffuse noxious inhibitory control (DNIC) values
Variation of Daily joint pain intensity
daily evaluation of the previous 24h pain on a numeric pain scale 0 to 100
Disease activity evaluated by the Disease Activity Score on 28 joints (DAS28)
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.
Disease activity evaluated by the Simple Disease Activity Index (SDAI)
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.
Disease activity evaluated by the Clinical Disease Activity Index (SDAI)
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).
Health Assessment Questionnaire (HAQ)
Rheumatoid Arthritis Impact of Disease score (RAID)
Hospital Anxiety and Depression scale
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
Coping Strategy Questionnaire: a 21-items self-report
Levels of cytokines
Levels of neurotrophins
Levels of miR21, miR-124, miR-146a and miR-155

Full Information

First Posted
January 11, 2019
Last Updated
May 3, 2023
Sponsor
University Hospital, Bordeaux
Collaborators
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT03815578
Brief Title
Evaluation of Pain Sensitization in Rheumatoid Arthritis: Analysis on a Cohort of Tofacitinib Treated Patients
Acronym
TOPRA
Official Title
Evaluation of Pain Sensitization in Rheumatoid Arthritis: Analysis on a Cohort of Tofacitinib Treated Patients
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
June 17, 2019 (Actual)
Primary Completion Date
April 28, 2023 (Actual)
Study Completion Date
April 28, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Bordeaux
Collaborators
Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
pain sensitization, Tofacitinib, miRNA

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rheumatoid Arthritis (RA) patients
Arm Type
Experimental
Arm Description
RA according to the ACR/EULAR 2010 classification criteria
Intervention Type
Other
Intervention Name(s)
Clinical examination
Intervention Description
Number of painful joints, Number of swollen joints, Patient Global assessment VAS (0 - 100) and Physician Global assessment VAS (0 - 100)
Intervention Type
Other
Intervention Name(s)
Pain assessment
Intervention Description
Pressure Pain Thresholds (PPTs), Mechanical Temporal Summation (MTS) and Diffuse Noxious Inhibitory Control (DNIC)
Intervention Type
Other
Intervention Name(s)
blood sample
Intervention Description
18 ml whole blood for ELISA analysis and miRNAs detection
Intervention Type
Other
Intervention Name(s)
Patient Reported Outcomes
Intervention Description
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 Measure Information:
Title
Variation of the mean Pressure Pain Thresholds (PPTs)
Time Frame
At 6 months from baseline
Secondary Outcome Measure Information:
Title
Variation of Mechanical Temporal Summation (MTS)
Time Frame
At 1, 3 and 6 months from baseline
Title
Variation of Pressure Pain Thresholds (PPTs)
Time Frame
At 1, 3 and 6 months from baseline
Title
Variation of Diffuse noxious inhibitory control (DNIC) values
Time Frame
At 1, 3 and 6 months from baseline
Title
Variation of Daily joint pain intensity
Description
daily evaluation of the previous 24h pain on a numeric pain scale 0 to 100
Time Frame
At 1, 3 and 6 months from baseline
Title
Disease activity evaluated by the Disease Activity Score on 28 joints (DAS28)
Description
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.
Time Frame
At 1, 3 and 6 months from baseline
Title
Disease activity evaluated by the Simple Disease Activity Index (SDAI)
Description
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.
Time Frame
At 1, 3 and 6 months from baseline
Title
Disease activity evaluated by the Clinical Disease Activity Index (SDAI)
Description
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).
Time Frame
At 1, 3 and 6 months from baseline
Title
Health Assessment Questionnaire (HAQ)
Time Frame
At 1, 3 and 6 months from baseline
Title
Rheumatoid Arthritis Impact of Disease score (RAID)
Time Frame
At 1, 3 and 6 months from baseline
Title
Hospital Anxiety and Depression scale
Description
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
Time Frame
At 1, 3 and 6 months from baseline
Title
Coping Strategy Questionnaire: a 21-items self-report
Time Frame
At 1, 3 and 6 months from baseline
Title
Levels of cytokines
Time Frame
At 3 and 6 months from baseline
Title
Levels of neurotrophins
Time Frame
At 3 and 6 months from baseline
Title
Levels of miR21, miR-124, miR-146a and miR-155
Time Frame
At 3 and 6 months from baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thierry SCHAEVERBEKE, Prof
Organizational Affiliation
CHU Bordeaux
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU de Bordeaux - Service de rhumatologie
City
Bordeaux
Country
France
Facility Name
CHU de Limoges - service de rhumatologie
City
Limoges
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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