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Impact of the Persistence of Inflammation at Doppler Ultrasound Level on the Structural Evolution of Erosion in Rheumatoid Arthritis Treated With Biotherapy

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
HR-pQCT
Sponsored by
Centre Hospitalier Universitaire de Saint Etienne
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Rheumatoid Arthritis focused on measuring Rheumatoid Arthritis, bDMARDs, biotherapy, remission, erosion

Eligibility Criteria

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

Inclusion Criteria:

  • Initial medical examination performed,
  • RA diagnosis according to the criteria of the ACR / EULAR 2010
  • Low or moderate disease activity with a DAS28 ≤ 4 since at least for 6 months
  • Patients with bDMARDs (Remicade®, Enbrel®, Humira®, Cimzia®, Simponi®, Ro-Actemra®, ou Orencia®) since at least 6 months and no change planned by the investigator,
  • Patient with at least one erosion on the head of the 2nd or 3rd metacarpal right or left,
  • Stable corticosteroids dose since at least 3 months less than or equal to 10 mg of prednisone equivalent,
  • Medical care and monitoring in the rheumatology department of the CHU of Saint-Etienne or the Edouard Herriot Hospital in Lyon,
  • written consent of patient

Exclusion Criteria:

  • Other diagnosis than RA,
  • Intravenous or intra-articular injection at the 2nd or 3rd metacarpophalangeal left or right during the 3 months prior to inclusion,
  • Surgery provided at the 2nd or 3rd metacarpophalangeal right or left within a year of inclusion,
  • Concomitant treatment with zoledronic acid (Aclasta) or denosumab (Prolia®)
  • Refusal of blood collection,
  • Pregnancy or breastfeeding women,

Sites / Locations

  • HCL - Hôpital EdouarD Herriot
  • CHU Saint-Etienne

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

active erosion

inactive erosion

Arm Description

HR-pQCT for measure bone parameters in "active erosion" group. The "active erosion" group will be defined by grades 2 and 3, ie by the presence of Doppler signals confluence in less than 50% of the synovial surface (grade 2) and in over 50% of the surface synovial for grade 3

HR-pQCT for measure bone parameters in "active erosion" group. The "inactive erosion" group will be defined by grades 0 and 1, ie the absence of Doppler signal for grade 0 and the presence of some non confluence Doppler signals for the grade 1

Outcomes

Primary Outcome Measures

Change in depth of the erosion
compare the change in the depth of the erosion of the second or third metacarpal head right or left at 12 months between patients with "active erosion" and those with "inactive erosion" in RA patients with low disease activity treated with bDMARD since at least 6 months (Remicade®, Enbrel®, Humira®, Cimzia®, Simponi®, Ro-Actemra®, or Orencia®).

Secondary Outcome Measures

Change in volume of erosion
compare the change in volume of erosion of the second or third metacarpal head right or left at 12 months between patients with "active erosion" and those with "inactive erosion" in RA patients with low disease activity treated with bDMARD since at least 6 months (Remicade®, Enbrel®, Humira®, Cimzia®, Simponi®, Ro-Actemra®, or Orencia®).
Change in width of erosion
compare the change in width of erosion of the second or third metacarpal head right or left at 12 months between patients with "active erosion" and those with "inactive erosion" in RA patients with low disease activity treated with bDMARD since at least 6 months (Remicade®, Enbrel®, Humira®, Cimzia®, Simponi®, Ro-Actemra®, or Orencia®).
Change in density parameter of bone microarchitecture
compare the change in density parameter of bone microarchitecture of erosion of the second or third metacarpal head right or left at 12 months between patients with "active erosion" and those with "inactive erosion" in RA patients with low disease activity treated with bDMARD since at least 6 months (Remicade®, Enbrel®, Humira®, Cimzia®, Simponi®, Ro-Actemra®, or Orencia®). Density parameter of bone microarchitecture is a composite outcome : Total mineral volumetric density (mg/ccm HA), Trabéculaire mineral volumetric density (mg/ccm HA), Cortical mineral volumetric density (mg/ccm HA), Trabecular Number (1/mm), Trabecular thickness (mm), Trabecular Separation (mm), Mean distance between trabeculae (mm), Presence of new erosions and volume

Full Information

First Posted
August 20, 2015
Last Updated
October 26, 2018
Sponsor
Centre Hospitalier Universitaire de Saint Etienne
Collaborators
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT02531061
Brief Title
Impact of the Persistence of Inflammation at Doppler Ultrasound Level on the Structural Evolution of Erosion in Rheumatoid Arthritis Treated With Biotherapy
Official Title
Impact of the Persistence of Inflammation at Doppler Ultrasound Level on the Structural Evolution of Erosion in Rheumatoid Arthritis Treated With Biotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
May 5, 2013 (Actual)
Primary Completion Date
November 29, 2017 (Actual)
Study Completion Date
November 29, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Saint Etienne
Collaborators
Pfizer

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Since biological disease-modifying anti-rheumatic drugs (bDMARDs) are available in rheumatoid arthritis (RA) strategy an emerging question is the definition of remission in RA. Today some criteria were already proposed and the last one was proposed in 2011. All these criteria integrated only clinical criteria without imaging assessment. In this context, ultrasound joint is daily performed without definition of remission. A discrepancy exists between clinical remission and persistence of active disease with ultrasound joint presence of a Doppler effect indicating inflammation and the risk of progression of joint damage. A definition of remission in RA could include erosions regression in subchondral bone (at best measured by high resolution peripheral quantitative computed tomography (HR-pQCT)). The main hypothesis is that the reduction of erosion size assessed by HR-pQCT will be observed only in the absence of local inflammation measured by Doppler ultrasound in the erosion. Tumor Necrosis Factor (TNF) blockers have strongly improved RA therapy outcome in terms of clinical improvement and structural damage (progression of radiographic lesions). Recent data showed that there could be joint bone rebuilt in case of inflammation suppression. HR-pQCT is a new technique emerging for bone erosions assessment in RA. Erosions size and volume could be reduced with anti-TNF, but with a large interindividual variability. There was no correlation between the activity of clinical or ultrasound synovium and evolution of erosion HR-pQCT.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid Arthritis, bDMARDs, biotherapy, remission, erosion

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
active erosion
Arm Type
Experimental
Arm Description
HR-pQCT for measure bone parameters in "active erosion" group. The "active erosion" group will be defined by grades 2 and 3, ie by the presence of Doppler signals confluence in less than 50% of the synovial surface (grade 2) and in over 50% of the surface synovial for grade 3
Arm Title
inactive erosion
Arm Type
Experimental
Arm Description
HR-pQCT for measure bone parameters in "active erosion" group. The "inactive erosion" group will be defined by grades 0 and 1, ie the absence of Doppler signal for grade 0 and the presence of some non confluence Doppler signals for the grade 1
Intervention Type
Device
Intervention Name(s)
HR-pQCT
Other Intervention Name(s)
Xtrem CT scanco
Intervention Description
The Xtrem CT scanco device is a HR-pQCT. It was initially used to measure bone density and quantify the bone architecture to 3D at the extremities of the human body. For the study, the device will be used to measure changes in erosion at the 2nd or 3rd metacarpal head. Only the patient's hand will be in contact with the medical device, the acquisition time will be 3 minutes.
Primary Outcome Measure Information:
Title
Change in depth of the erosion
Description
compare the change in the depth of the erosion of the second or third metacarpal head right or left at 12 months between patients with "active erosion" and those with "inactive erosion" in RA patients with low disease activity treated with bDMARD since at least 6 months (Remicade®, Enbrel®, Humira®, Cimzia®, Simponi®, Ro-Actemra®, or Orencia®).
Time Frame
baseline from 1 year
Secondary Outcome Measure Information:
Title
Change in volume of erosion
Description
compare the change in volume of erosion of the second or third metacarpal head right or left at 12 months between patients with "active erosion" and those with "inactive erosion" in RA patients with low disease activity treated with bDMARD since at least 6 months (Remicade®, Enbrel®, Humira®, Cimzia®, Simponi®, Ro-Actemra®, or Orencia®).
Time Frame
baseline from 1 year
Title
Change in width of erosion
Description
compare the change in width of erosion of the second or third metacarpal head right or left at 12 months between patients with "active erosion" and those with "inactive erosion" in RA patients with low disease activity treated with bDMARD since at least 6 months (Remicade®, Enbrel®, Humira®, Cimzia®, Simponi®, Ro-Actemra®, or Orencia®).
Time Frame
baseline from 1 year
Title
Change in density parameter of bone microarchitecture
Description
compare the change in density parameter of bone microarchitecture of erosion of the second or third metacarpal head right or left at 12 months between patients with "active erosion" and those with "inactive erosion" in RA patients with low disease activity treated with bDMARD since at least 6 months (Remicade®, Enbrel®, Humira®, Cimzia®, Simponi®, Ro-Actemra®, or Orencia®). Density parameter of bone microarchitecture is a composite outcome : Total mineral volumetric density (mg/ccm HA), Trabéculaire mineral volumetric density (mg/ccm HA), Cortical mineral volumetric density (mg/ccm HA), Trabecular Number (1/mm), Trabecular thickness (mm), Trabecular Separation (mm), Mean distance between trabeculae (mm), Presence of new erosions and volume
Time Frame
baseline from 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Initial medical examination performed, RA diagnosis according to the criteria of the ACR / EULAR 2010 Low or moderate disease activity with a DAS28 ≤ 4 since at least for 6 months Patients with bDMARDs (Remicade®, Enbrel®, Humira®, Cimzia®, Simponi®, Ro-Actemra®, ou Orencia®) since at least 6 months and no change planned by the investigator, Patient with at least one erosion on the head of the 2nd or 3rd metacarpal right or left, Stable corticosteroids dose since at least 3 months less than or equal to 10 mg of prednisone equivalent, Medical care and monitoring in the rheumatology department of the CHU of Saint-Etienne or the Edouard Herriot Hospital in Lyon, written consent of patient Exclusion Criteria: Other diagnosis than RA, Intravenous or intra-articular injection at the 2nd or 3rd metacarpophalangeal left or right during the 3 months prior to inclusion, Surgery provided at the 2nd or 3rd metacarpophalangeal right or left within a year of inclusion, Concomitant treatment with zoledronic acid (Aclasta) or denosumab (Prolia®) Refusal of blood collection, Pregnancy or breastfeeding women,
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hubert Marotte, PhD
Organizational Affiliation
CHU Saint-Etienne
Official's Role
Principal Investigator
Facility Information:
Facility Name
HCL - Hôpital EdouarD Herriot
City
Lyon
Country
France
Facility Name
CHU Saint-Etienne
City
Saint-Etienne
ZIP/Postal Code
42055
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Impact of the Persistence of Inflammation at Doppler Ultrasound Level on the Structural Evolution of Erosion in Rheumatoid Arthritis Treated With Biotherapy

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