## Protocol Section
### Identification Module
**NCT ID:** NCT04727879

**Acronym:** BAOBAB

**Brief Title:** Immunopathology of Polymyalgia Rheumatica on Shoulder Bursae's Biopsies

**Official Title:** Beyond Analysis Of Blood Sample, to Approach Immunopathology of Polymyalgia Rheumatica on Shoulder Bursae's Biopsies: the BAOBAB Study

#### Organization Study ID Info
**ID:** 29BRC20.0158
#### Organization
**Class:** OTHER
**Full Name:** University Hospital, Brest
### Status Module
#### Completion Date
**Date:** 2022-08-13

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-08-01

**Type:** ACTUAL

**Last Update Submit Date:** 2023-07-28

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2022-07-13

**Type:** ACTUAL

#### Start Date
**Date:** 2021-04-07

**Type:** ACTUAL

**Status Verified Date:** 2023-07

#### Study First Post Date
**Date:** 2021-01-27
**Type:** ACTUAL
**Study First Submit Date:** 2021-01-07
**Study First Submit QC Date:** 2021-01-26
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** University Hospital, Brest

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**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

### Conditions Module

**Conditions:**

- Polymyalgia Rheumatica

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** BASIC_SCIENCE

#### Enrollment Info

**Count:** 20

**Type:** ACTUAL

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**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.

**Intervention Names:**

- Procedure: Synovial membrane biopsy with puncture of synovial fluid

- Procedure: Joint fluid sampling

- Procedure: Blood sample

**Label:** PMR

**Type:** OTHER

#### Arm Group 2

**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 Names:**

- Procedure: Synovial membrane biopsy with puncture of synovial fluid

- Procedure: Blood sample

**Label:** Control

**Type:** OTHER

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Control

- PMR

**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.

**Name:** Synovial membrane biopsy with puncture of synovial fluid

**Type:** PROCEDURE

#### Intervention 2

**Arm Group Labels:**

- PMR

**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.

**Name:** Joint fluid sampling

**Type:** PROCEDURE

#### Intervention 3

**Arm Group Labels:**

- Control

- PMR

**Description:** A blood sample taken during routine care and unused will also be collected from patients and controls for immunoassays.

**Name:** Blood sample

**Type:** PROCEDURE

### Outcomes Module

#### Primary Outcomes

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

**Measure:** IL-6 marking

**Time Frame:** Day 0

#### Secondary Outcomes

**Measure:** Cytokinic (other than IL-6) infiltration of tissues

**Time Frame:** Day 0

**Measure:** Serum cytokine levels

**Time Frame:** Day 0

**Measure:** Cytokine levels in joint or synovial fluid

**Time Frame:** Day 0

**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.

**Measure:** Tissue distribution of lymphocyte subpopulations by using the Hyperion mass cytometer (analysis of the intensity of the markings)

**Time Frame:** Day 0

**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.

**Measure:** Serum distribution of lymphocyte subpopulations by using the HELIOS mass cytometer (analysis of the intensity of the markings)

**Time Frame:** Day 0

**Description:** Analysis of membrane markers related to immunosenescence in percent of cells expressing the marker and in MFI (Mean fluorescence intensity) by hyperion technology.

**Measure:** Analysis of immunosenescence markers in tissues by HYPERION technology

**Time Frame:** Day 0

**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).

**Measure:** Analysis of target molecules of treatments under study in PPR by ELISA technique

**Time Frame:** Day 0

**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)

**Measure:** Analysis of target molecules of treatments under study in PPR by proteomic techniques

**Time Frame:** Day 0

**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.

**Measure:** Complications of subacromio-deltoid purse in the 72h after biopsies : M1 phone call

**Time Frame:** Month 1

### Eligibility Module

**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

**Minimum Age:** 50 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Brest

**Country:** France

**Facility:** CHU de Brest - Service de rhumatologie

**Zip:** 29200

### IPD Sharing Statement Module

**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.

**Description:** All collected data that underlie results in a publication

**Info Types:**

- STUDY_PROTOCOL

**IPD Sharing:** YES

**Time Frame:** Data will be available beginning three years and ending fifteen years following the final study report completion

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009135

- Term: Muscular Diseases

- ID: D000009140

- Term: Musculoskeletal Diseases

- ID: D000012216

- Term: Rheumatic Diseases

- ID: D000003240

- Term: Connective Tissue Diseases

- ID: D000020293

- Term: Vasculitis, Central Nervous System

- ID: D000020274

- Term: Autoimmune Diseases of the Nervous System

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000002561

- Term: Cerebrovascular Disorders

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000001167

- Term: Arteritis

- ID: D000014657

- Term: Vasculitis

- ID: D000017445

- Term: Skin Diseases, Vascular

- ID: D000012871

- Term: Skin Diseases

- ID: D000001327

- Term: Autoimmune Diseases

- ID: D000007154

- Term: Immune System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC05

- Name: Musculoskeletal Diseases

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M13995

- Name: Polymyalgia Rheumatica

- Relevance: HIGH

- As Found: Polymyalgia Rheumatica

- ID: M16472

- Name: Giant Cell Arteritis

- Relevance: HIGH

- As Found: Polymyalgia Rheumatica

- ID: M4475

- Name: Arteritis

- Relevance: LOW

- As Found: Unknown

- ID: M12092

- Name: Muscular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12097

- Name: Musculoskeletal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15045

- Name: Rheumatic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6323

- Name: Collagen Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6464

- Name: Connective Tissue Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17405

- Name: Vasculitis

- Relevance: LOW

- As Found: Unknown

- ID: M22106

- Name: Vasculitis, Central Nervous System

- Relevance: LOW

- As Found: Unknown

- ID: M4629

- Name: Autoimmune Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M22094

- Name: Autoimmune Diseases of the Nervous System

- Relevance: LOW

- As Found: Unknown

- ID: M5810

- Name: Cerebrovascular Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15674

- Name: Skin Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M19714

- Name: Skin Diseases, Vascular

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T2487

- Name: Giant Cell Arteritis

- Relevance: HIGH

- As Found: Polymyalgia Rheumatica

### Condition Browse Module - Meshes

- ID: D000011111

- Term: Polymyalgia Rheumatica

- ID: D000013700

- Term: Giant Cell Arteritis

### Intervention Browse Module - Browse Branches

- Abbrev: Analg

- Name: Analgesics

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Infl

- Name: Anti-Inflammatory Agents

### Intervention Browse Module - Browse Leaves

- ID: M4032

- Name: Analgesics

- Relevance: LOW

- As Found: Unknown

- ID: M6569

- Name: Cortisone

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
