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Immunopathology of Polymyalgia Rheumatica on Shoulder Bursae's Biopsies (BAOBAB)

Primary Purpose

Polymyalgia Rheumatica

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Synovial membrane biopsy with puncture of synovial fluid
Joint fluid sampling
Blood sample
Sponsored by
University Hospital, Brest
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Polymyalgia Rheumatica

Eligibility Criteria

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

For everyone :

  • Signed consent
  • Patients over 50

Inclusion criteria :

For case patients:

  • Addressed for PMR (diagnosis OR relapse)
  • Score greater than or equal to 4 (without ultrasound criteria) or greater than or equal to 6 (with ultrasound criteria), according to the ACR / EULAR 2012 criteria for polymyalgia rheumatica, and suffering from bilateral scapular pain as well as an increased CRP level .
  • Thickening of more than 2mm at least one shoulder bursae in ultrasound
  • DAS-PPR> = 10

For witnesses:

- Shoulder surgery scheduled for mechanical pathology

Exclusion criteria :

For everyone :

  • MRI with Gadolinium injection in the previous month- Clinical or paraclinical signs of giant cell arteritis
  • Patient under protective measure or unable to consent
  • Active cancer
  • Active infection

For the cases:

- History of biotherapy treatment

For witnesses:

  • History of inflammatory rheumatism
  • Active inflammatory rheumatism

Sites / Locations

  • CHU de Brest - Service de rhumatologie

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

PMR

Control

Arm Description

Patients with PMR will be offered biopsy of the synovial membrane with puncture of synovial fluid during cortisone infiltration for analgesic purposes. In case of associated peripheric arthritis, the patient will also be offered a joint fluid sample during a cortisonic infiltration for analgesic purposes, performed as part of routine care The study-specific examination that is not part of current practice is the synovial biopsy performed during the cortisonic infiltration procedure.

Witnesses recruited into the orthopedic surgery department will be offered a synovial membrane biopsy during a shoulder surgery in the context of mechanical pathology.

Outcomes

Primary Outcome Measures

IL-6 marking
The main evaluation criterion is the intensity of the tissue IL-6 marking on the subacromio-deltoid bursa sections using the Hyperion technique.

Secondary Outcome Measures

Cytokinic (other than IL-6) infiltration of tissues
Serum cytokine levels
Cytokine levels in joint or synovial fluid
Tissue distribution of lymphocyte subpopulations by using the Hyperion mass cytometer (analysis of the intensity of the markings)
Fragments of the synovial membrane taken from patients and controls will be sent to the pathology laboratory. They will be fixed and slides covering the inflammatory region of interest will be prepared. These slides will be marked with antibodies directed against: - CD20, CD27, CD38, CD24, CD21, CD95, CD23, IgM, Tbet for B lymphocytes; - CD3, CD4, CD8, CD25, CD45RA, CD62L, CD28, FoxP3, CCR7, CD45RO and Bcl-2 for T lymphocytes; - CD14, CD11b and CD11c for monocytes; - CD66b for granulocytes and coupled to heavy metals and analyzed by the Hyperion mass cytometer. The intensity of the markings will be analyzed using the usual Hyperion analysis techniques.
Serum distribution of lymphocyte subpopulations by using the HELIOS mass cytometer (analysis of the intensity of the markings)
Whole blood will be centrifuged and serum will be collected. Antibodies directed against: - CD20, CD27, CD38, CD24, CD21, CD95, CD23, IgM, Tbet for B lymphocytes; - CD3, CD4, CD8, CD25, CD45RA, CD62L, CD28, FoxP3, CCR7, CD45RO and Bcl-2 for T lymphocytes; - CD14, CD11b and CD11c for monocytes; - CD66b for granulocytes, aand Hnd coupled with heavy metals will be added to it before analysis by the HELIOS mass cytometer. The intensity of the markings will be analyzed using the usual HELIOS analysis techniques.
Analysis of immunosenescence markers in tissues by HYPERION technology
Analysis of membrane markers related to immunosenescence in percent of cells expressing the marker and in MFI (Mean fluorescence intensity) by hyperion technology.
Analysis of target molecules of treatments under study in PPR by ELISA technique
The target molecules of treatments under study in PPR (CTLA-4 for abatacept, janus kinases 1 and 2 for baricitinib) will be analyzed by ELISA techniques (concentration).
Analysis of target molecules of treatments under study in PPR by proteomic techniques
The target molecules of treatments under study in PPR (CTLA-4 for abatacept, janus kinases 1 and 2 for baricitinib) will be analyzed by protéomic techniques (cytometry, % of cells expressing the marker, MFI)
Complications of subacromio-deltoid purse in the 72h after biopsies : M1 phone call
The expected complications related to the synovial biopsy are: Pain at the biopsy site, Hematoma at the biopsy site, Functional impotence of the shoulder, on the biopsy side, greater than 72h, Hypoesthesia, dysesthesia at the biopsy site, Skin rash within 72h following the infiltration, Hypertensive surge documented within 72 hours of the infiltration, In case of pre-existing diabetes, diabetes imbalance within 72 hours of the infiltration.

Full Information

First Posted
January 7, 2021
Last Updated
July 28, 2023
Sponsor
University Hospital, Brest
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1. Study Identification

Unique Protocol Identification Number
NCT04727879
Brief Title
Immunopathology of Polymyalgia Rheumatica on Shoulder Bursae's Biopsies
Acronym
BAOBAB
Official Title
Beyond Analysis Of Blood Sample, to Approach Immunopathology of Polymyalgia Rheumatica on Shoulder Bursae's Biopsies: the BAOBAB Study
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
April 7, 2021 (Actual)
Primary Completion Date
July 13, 2022 (Actual)
Study Completion Date
August 13, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Brest

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
The work carried out at the Brest University Hospital on serum immunological changes in patients with polymyalgia rheumatica (PMR) (based on clinical protocols TENOR, SEMAPHORE, THEN) made it possible to describe the changes in the distribution of lymphocyte subpopulations and cytokine levels during PPR, before and then under treatment compared to controls. However, in systemic autoimmune or inflammatory pathologies, serum immunological mechanisms are rarely a reflection of intra-tissue mechanisms. In the specific case of PMR, there are few data concerning muscular or joint immunological modifications. The investigators now wish to study the immunological modifications occurring at the tissue sites of interest, in particular in the shoulder bursae

6. Conditions and Keywords

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

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
PMR
Arm Type
Other
Arm Description
Patients with PMR will be offered biopsy of the synovial membrane with puncture of synovial fluid during cortisone infiltration for analgesic purposes. In case of associated peripheric arthritis, the patient will also be offered a joint fluid sample during a cortisonic infiltration for analgesic purposes, performed as part of routine care The study-specific examination that is not part of current practice is the synovial biopsy performed during the cortisonic infiltration procedure.
Arm Title
Control
Arm Type
Other
Arm Description
Witnesses recruited into the orthopedic surgery department will be offered a synovial membrane biopsy during a shoulder surgery in the context of mechanical pathology.
Intervention Type
Procedure
Intervention Name(s)
Synovial membrane biopsy with puncture of synovial fluid
Intervention Description
The biopsy of the shoulder bursae will be carried out thanks to a device Tru-cut (Tru-Cut Biopsy Needle), minimally invasive, introduced, as during an infiltration, within the bursa serosa.
Intervention Type
Procedure
Intervention Name(s)
Joint fluid sampling
Intervention Description
In case of associated peripheric arthritis, the patient will also be offered a sample of joint fluid during a cortisonic infiltration for analgesic purposes, performed as part of routine care.
Intervention Type
Procedure
Intervention Name(s)
Blood sample
Intervention Description
A blood sample taken during routine care and unused will also be collected from patients and controls for immunoassays.
Primary Outcome Measure Information:
Title
IL-6 marking
Description
The main evaluation criterion is the intensity of the tissue IL-6 marking on the subacromio-deltoid bursa sections using the Hyperion technique.
Time Frame
Day 0
Secondary Outcome Measure Information:
Title
Cytokinic (other than IL-6) infiltration of tissues
Time Frame
Day 0
Title
Serum cytokine levels
Time Frame
Day 0
Title
Cytokine levels in joint or synovial fluid
Time Frame
Day 0
Title
Tissue distribution of lymphocyte subpopulations by using the Hyperion mass cytometer (analysis of the intensity of the markings)
Description
Fragments of the synovial membrane taken from patients and controls will be sent to the pathology laboratory. They will be fixed and slides covering the inflammatory region of interest will be prepared. These slides will be marked with antibodies directed against: - CD20, CD27, CD38, CD24, CD21, CD95, CD23, IgM, Tbet for B lymphocytes; - CD3, CD4, CD8, CD25, CD45RA, CD62L, CD28, FoxP3, CCR7, CD45RO and Bcl-2 for T lymphocytes; - CD14, CD11b and CD11c for monocytes; - CD66b for granulocytes and coupled to heavy metals and analyzed by the Hyperion mass cytometer. The intensity of the markings will be analyzed using the usual Hyperion analysis techniques.
Time Frame
Day 0
Title
Serum distribution of lymphocyte subpopulations by using the HELIOS mass cytometer (analysis of the intensity of the markings)
Description
Whole blood will be centrifuged and serum will be collected. Antibodies directed against: - CD20, CD27, CD38, CD24, CD21, CD95, CD23, IgM, Tbet for B lymphocytes; - CD3, CD4, CD8, CD25, CD45RA, CD62L, CD28, FoxP3, CCR7, CD45RO and Bcl-2 for T lymphocytes; - CD14, CD11b and CD11c for monocytes; - CD66b for granulocytes, aand Hnd coupled with heavy metals will be added to it before analysis by the HELIOS mass cytometer. The intensity of the markings will be analyzed using the usual HELIOS analysis techniques.
Time Frame
Day 0
Title
Analysis of immunosenescence markers in tissues by HYPERION technology
Description
Analysis of membrane markers related to immunosenescence in percent of cells expressing the marker and in MFI (Mean fluorescence intensity) by hyperion technology.
Time Frame
Day 0
Title
Analysis of target molecules of treatments under study in PPR by ELISA technique
Description
The target molecules of treatments under study in PPR (CTLA-4 for abatacept, janus kinases 1 and 2 for baricitinib) will be analyzed by ELISA techniques (concentration).
Time Frame
Day 0
Title
Analysis of target molecules of treatments under study in PPR by proteomic techniques
Description
The target molecules of treatments under study in PPR (CTLA-4 for abatacept, janus kinases 1 and 2 for baricitinib) will be analyzed by protéomic techniques (cytometry, % of cells expressing the marker, MFI)
Time Frame
Day 0
Title
Complications of subacromio-deltoid purse in the 72h after biopsies : M1 phone call
Description
The expected complications related to the synovial biopsy are: Pain at the biopsy site, Hematoma at the biopsy site, Functional impotence of the shoulder, on the biopsy side, greater than 72h, Hypoesthesia, dysesthesia at the biopsy site, Skin rash within 72h following the infiltration, Hypertensive surge documented within 72 hours of the infiltration, In case of pre-existing diabetes, diabetes imbalance within 72 hours of the infiltration.
Time Frame
Month 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
For everyone : Signed consent Patients over 50 Inclusion criteria : For case patients: Addressed for PMR (diagnosis OR relapse) Score greater than or equal to 4 (without ultrasound criteria) or greater than or equal to 6 (with ultrasound criteria), according to the ACR / EULAR 2012 criteria for polymyalgia rheumatica, and suffering from bilateral scapular pain as well as an increased CRP level . Thickening of more than 2mm at least one shoulder bursae in ultrasound DAS-PPR> = 10 For witnesses: - Shoulder surgery scheduled for mechanical pathology Exclusion criteria : For everyone : MRI with Gadolinium injection in the previous month- Clinical or paraclinical signs of giant cell arteritis Patient under protective measure or unable to consent Active cancer Active infection For the cases: - History of biotherapy treatment For witnesses: History of inflammatory rheumatism Active inflammatory rheumatism
Facility Information:
Facility Name
CHU de Brest - Service de rhumatologie
City
Brest
ZIP/Postal Code
29200
Country
France

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All collected data that underlie results in a publication
IPD Sharing Time Frame
Data will be available beginning three years and ending fifteen years following the final study report completion
IPD Sharing Access Criteria
Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement.

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Immunopathology of Polymyalgia Rheumatica on Shoulder Bursae's Biopsies

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