## Protocol Section
### Identification Module
**NCT ID:** NCT06432556

**Acronym:** MastCellHet

**Brief Title:** Study of Cellular Heterogeneity in Patients With Mastocytosis

**Official Title:** Study of Cellular Heterogeneity in Patients With Mastocytosis (MastCellHet) Mastocytosis Cell Heterogeneity

#### Organization Study ID Info
**ID:** RC31/23/0362
#### Organization
**Class:** OTHER
**Full Name:** University Hospital, Toulouse
#### Secondary ID Infos
**Domain:** ID-RCB
**ID:** 2024-A00021-46
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2026-06-15

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-29

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-21

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-06-08

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-29
**Type:** ACTUAL
**Study First Submit Date:** 2024-04-29
**Study First Submit QC Date:** 2024-05-21
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** University Hospital, Toulouse

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** This study will aim to study the heterogeneity of skin-resident mast cells and of blood circulating hematopoietic progenitors in patients suffering from isolated Cutaneous Mastocytosis and from systemic Mastocytosis with skin lesions.

**Detailed Description:** Mastocytosis is a rare disease caused by abnormal mast cell accumulation/proliferation. Its clinical features are very heterogeneous. Among adult patients, 15% present an isolated cutaneous mastocytosis (CM), while 85% of them present a systemic mastocytosis (SM) with cutaneous lesions. In addition, regardless of the diagnosis (i.e., CM or SM), it is frequent to observe mast cell-dependent symptoms of variable severity, ranging from gastrointestinal discomfort to life-threatening reactions. To date, the origin of such heterogeneous manifestations in adult patients is still elusive. Researchers hypothesize that the heterogeneity in mastocytosis symptoms might originate, at least in part, from a broad diversity of mast cell populations in patients. This study will aim to uncover heterogeneity of skin-resident mast cells and of blood circulating hematopoietic progenitors in patients suffering from isolated CM or SM with skin lesions. Patients with isolated CM and patients with SM with cutaneous involvement will be recruited from the Mastocytosis Expert Center of Toulouse.

Cluster of Differentiation (CD) 45+ cells from skin biopsies and CD 34+ cells from blood will be isolated by magnetic cell sorting for scRNAseq. Bioinformatics analysis pipeline will be used in order to analyze the cellular heterogeneity of skin lesions and blood from CM and SM patients by comparing their transcriptomic signatures. Using trajectories analysis, the researchers will then deduce infer a differentiation pathway between blood progenitors and cutaneous mast cells at the patient level. Researchers will then confirm the expression of identified relevant biomarkers by highly multiplexed imaging in frozen skin biopsies from CM patients and from SM patients.

### Conditions Module

**Conditions:**

- Mastocytosis

**Keywords:**

- Mastocytosis

- Mast cells

- Cellular heterogeneity

- CD 45+

- CD 34+

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** OTHER

#### Enrollment Info

**Count:** 26

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Genetic: scRNAseq

- Procedure: two Skin biopsies

**Label:** patients with isolated cutaneous mastocytosis with associated skin involvement - RNAseq

**Type:** OTHER

#### Arm Group 2

**Intervention Names:**

- Procedure: one Skin biopsies

**Label:** patients with mastocytosis indolent systemic with associated skin involvement

**Type:** OTHER

#### Arm Group 3

**Intervention Names:**

- Procedure: one Skin biopsies

**Label:** patients with isolated cutaneous mastocytosis with associated skin involvement

**Type:** OTHER

#### Arm Group 4

**Intervention Names:**

- Genetic: scRNAseq

- Procedure: two Skin biopsies

**Label:** patients with mastocytosis indolent systemic with associated skin involvement - RNAseq

**Type:** OTHER

### Interventions

#### Intervention 1

**Arm Group Labels:**

- patients with isolated cutaneous mastocytosis with associated skin involvement - RNAseq

- patients with mastocytosis indolent systemic with associated skin involvement - RNAseq

**Description:** A blood test tube (only for scRNAseq, 2 tubes of 10 ml per patient)

**Name:** scRNAseq

**Type:** GENETIC

#### Intervention 2

**Arm Group Labels:**

- patients with isolated cutaneous mastocytosis with associated skin involvement - RNAseq

- patients with mastocytosis indolent systemic with associated skin involvement - RNAseq

**Description:** 2 skin biopsies from a lesional area

**Name:** two Skin biopsies

**Type:** PROCEDURE

#### Intervention 3

**Arm Group Labels:**

- patients with isolated cutaneous mastocytosis with associated skin involvement

- patients with mastocytosis indolent systemic with associated skin involvement

**Description:** 1 skin biopsies from a lesional area

**Name:** one Skin biopsies

**Type:** PROCEDURE

### Outcomes Module

#### Other Outcomes

**Description:** through advanced imaging techniques (multiplexed imaging), marker in patients with isolated cutaneous mastocytosis and systemic mastocytosis will be identified compared with control sample

**Measure:** marker

**Time Frame:** 24 month and one week

**Description:** through advanced imaging techniques (multiplexed imaging), marker in patients with isolated cutaneous mastocytosis will be identified compared with control sample

**Measure:** marker - isolated cutaneous mastocytosis

**Time Frame:** 24 month and one week

**Description:** through advanced imaging techniques (multiplexed imaging), marker in patients with systemic mastocytosis will be identified compared with control sample

**Measure:** marker - systemic mastocytosis

**Time Frame:** 24 month and one week

#### Primary Outcomes

**Description:** This study aims to examine the diversity of CD 45+ cells in the skin and CD 34+ cells in the circulating blood in patients. The approach used will be single cell sequencing (scRNAseq) to identify the transcriptomic profiles of the different cell populations in these two types of mastocytosis.

**Measure:** Study of the diversity of skin CD 45+ cells and circulating blood CD 34+ cells

**Time Frame:** 24 month and one week

#### Secondary Outcomes

**Description:** This part of the study will focus on analyzing common or differential genetic transcripts between patients with isolated cutaneous mastocytosis and those with systemic mastocytosis. The aim is to understand the underlying molecular differences between these two forms of the disease.

**Measure:** Study of common or differential transcripts

**Time Frame:** 24 month and one week

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Criteria related to the study population:
* Subject affiliated with a social security or insurance scheme
* Subject who has given written consent to his participation in the study
* Criteria related to the studied pathology:
* Subject diagnosed with isolated cutaneous or indolent systemic mastocytosis with associated skin involvement defined according to World Health Organization criteria (and/or international criteria for cutaneous mastocytosis)
* Subjects whose KIT mutation status is known in the skin, bone marrow, and blood

Exclusion Criteria:

* Criteria related to the study population:
* Sun exposure of the biopsied areas expected within the 4 weeks preceding
* Subjects who have had exposure to sunlight or artificial UV radiation within the 2 weeks preceding inclusion at the biopsied areas
* Adult patients under legal protection, guardianship, or curatorship
* Pregnant or lactating women
* Criteria related to the studied pathology:
* Subjects with an advanced version of the pathology or advanced systemic mastocytosis (SAMA)
* Subjects with a known history of allergy or intolerance to local anesthetics
* Subjects who have previously shown abnormalities in skin healing or any other contraindication to skin biopsy
* Subjects with recognized addiction to alcoholism or drug abuse
* Subjects with a hereditary or acquired disorder of hemostasis
* Subjects with a severe or acute chronic condition judged by the investigator as incompatible with the trial
* Subjects presenting a clinically incompatible immune deficiency with the study
* Patients without a well-established diagnosis of mastocytosis
* Patients included in a therapeutic study for indolent systemic mastocytosis
* Treatment-related criteria:
* Any topical or systemic treatment for atopic dermatitis (including phototherapy) ongoing or stopped at least 14 days before the inclusion visit
* Systemic corticosteroids within the 4 weeks preceding the inclusion visit
* Ongoing systemic treatment likely to interfere with the healing process
* Subjects who have undergone physical treatment (radiotherapy, etc.) on the biopsy area in the past 6 months
* History of treatment or concomitant treatment that may interfere with the conduct of the study as determined by the investigator

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** livideanu.c@chu-toulouse.fr

**Name:** Cristina Bulai Livideanu, MD

**Phone:** 0567778138

**Phone Ext:** +33

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Toulouse

**Country:** France

**Facility:** University Hospital

**Zip:** 31059

#### Overall Officials

**Official 1:**

**Affiliation:** Toulouse univiversity hospital

**Name:** Cristina Bulai Livideanu, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009372

- Term: Neoplasms, Connective Tissue

- ID: D000018204

- Term: Neoplasms, Connective and Soft Tissue

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000090362

- Term: Mast Cell Activation Disorders

- ID: D000007154

- Term: Immune System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M11399

- Name: Mastocytosis

- Relevance: HIGH

- As Found: Mastocytosis

- ID: M12317

- Name: Neoplasms, Connective Tissue

- Relevance: LOW

- As Found: Unknown

- ID: M20350

- Name: Neoplasms, Connective and Soft Tissue

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M2776

- Name: Mast Cell Activation Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T3626

- Name: Mastocytosis

- Relevance: HIGH

- As Found: Mastocytosis

### Condition Browse Module - Meshes

- ID: D000008415

- Term: Mastocytosis

### Misc Info Module

- Version Holder: 2024-05-31
