Innate Immunity, MIcrobiota and Inovative Treatments in Endometriosis

NCT07078435 | Not Yet Recruiting DMC

• 1 other identifier: 38RC25.0052
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Endometriosis is a chronic inflammatory, polygenic, and multifactorial disease affecting approximately 10% of women of reproductive age, corresponding to over one million women in France. Endometriosis profoundly impairs the health and quality of life of affected individuals and carries a significant socio-economic burden, making it a major public health concern. To date, the pathogenesis and prognostic factors of disease progression remain poorly understood. Despite current treatment options, which are based on hormonal therapy or surgery, resistance and recurrence are frequent, underscoring the urgent need for innovative therapeutic strategies. The hypothesis of retrograde menstruation of endometrial cells, among other proposed theories, appears insufficient to fully explain the development of the disease. Immunological factors may be implicated. Endometriosis is characterized by the presence of endometriotic tissue outside the uterine cavity- within the peritoneal cavity or at distant sites-forming lesions that, like eutopic endometrium, contain infiltrating immune cells, with varying compositions across menstrual cycle phases. Although data remain scarce, the literature points to several key mechanisms: Inflammation and innate immunity with the dendritic cells, that initiate and orchestrate immune responses, appear to be present in different proportions and exhibit altered phenotypes in endometriotic tissue compared to healthy tissue. Macrophages, essential for phagocytosis, tissue repair, and the resolution of inflammation, also show functional and phenotypic modulation. In particular, efferocytosis-their ability to clear apoptotic cells-is impaired, and an imbalance in M1/M2 polarization has been described, potentially facilitating menstrual cell escape. The local microenvironment is characterized by altered cytokine and chemokine profiles. Natural Killer cells exhibit disrupted expression patterns of activating and degranulation capacity. Microbiota: Many studies suggest a potential role for the intestinal microbiota in the initiation and/or promotion of endometriosis. Patients frequently exhibit gut dysbiosis, marked by reduced microbial diversity. Resolution of Inflammation: Endometriosis may be associated with defective resolution of inflammation. Resolutive pharmacology involves the use of pro-resolving factors to exert a therapeutic effect by accelerating or stimulating the resolution of inflammation. The interplay between local inflammation, the gut microbiota, and disease progression remains incompletely elucidated. A comprehensive phenotypic and functional characterization of immune cells-particularly innate immune cells (dendritic cells, macrophages, Natural Killer cells) - in parallel with microbiome profiling and clinical outcome data, may yield novel insights into disease mechanisms and support the development of pro-resolutive therapeutic strategies that may be of interest in endometriosis. Study Design This will be a monocentric (at Grenoble University Hospital), open-label, prospective experimental study with a control arm. The primary objective is to identify immune biomarkers associated with endometriosis. Secondary objectives include:

1. 1.Identification of immune biomarkers associated with clinical outcomes in endometriosis.
2. 2.Characterization of the immunogenetic KIR/HLA (Killer Immunoglobulin-like Receptors / Human Leukocyte Antigen) system in both study groups.
3. 3.Analysis of stromal cells, apoptosis, macrophage efferocytosis, and their responsiveness to pro-resolutive factors in both groups.
4. 4.Identification of a characteristic bacterial gut microbiota profile at diagnosis in women with endometriosis versus controls, and/or profiles associated with one-year clinical outcomes (favorable vs unfavorable), as well as temporal microbiota trajectories over one year in relation to clinical response.

Conditions

Endometriosis; Immunity; Microbiota

Keywords

endometriosis; surgery; immunity; efferocytose; microbiota

Outcome Measures

Primary Outcomes (1)

• To identify immune biomarkers associated with endometriosis.

  The primary endpoint is to describe and compare innate immune cells (with dendritic cells, macrophages, natural killers cells, lymphocytes) according to tissue (blood, peritoneal lavage, biopsies of endometrium and more or less endometriosis) and for each tissue according to the presence of endometriosis ("endometriosis" and "control" groups). The variables analyzed will be the frequencies of different subpopulations of dendritic cells (cDC1, cDC2, PDC, inflammatory DC), macrophages (M0, M1, M2), and effectors (NK, iNKT, lymphocytes T); as well as their level of maturity or activation, assessed by their expression of surface markers relevant.

  The day of inclusion with the sample during the surgery

Secondary Outcomes (5)

• To identify immune biomarkers associated with clinical response in endometriosis

  The samples are collected during the day of surgery

• To characterize the KIR/HLA (Human Leukocyte Antigen) immunogenetic system in both "endometriosis" and "control" groups

  The sample are collected the surgery day.

• To characterize stromal cells, their apoptosis.

  The samples are collected during the surgery day

• To characterize macrophage efferocytosis this their response to pro-resolving factors in both "endometriosis" and "control" groups.

  The samples are collected during the surgery day

• To identify a profile of bacterial intestinal microbiota at diagnosis characteristic of "endometriosis" patients compared with "controls", and/or associated with clinical response at 1 year (favorable or unfavorable).

  The stools samples are collected the surgery day in hospitalisation and at the one year of follow up.

Study Arms (2)

Endometriosis group

ACTIVE COMPARATOR

Patients in "endometriosis group" are aged 18-42 years and suffer symptomatic endometriosis that requires a surgery indication (due to persistent symptoms despite medical treatment and/or risk of organ damage). These patients generally undergo hormonal therapy, but this must be discontinued at least one month prior to surgery. The surgery is scheduled to take place during the luteal phase. Patients don't take a immunosuppressor, antibiotic or present inflammatory bowel disease, recent infection, pregnancy

Procedure: surgery (any volume) and / or pharmaceuticals treatment initiated or planned or only dynamic observation, in accordance with current clinical guidelines; Biological: Blood test; Biological: Stool samples

Control group

ACTIVE COMPARATOR

Patients in "control group" are aged 18-42 years and don't suffer endometriosis that requires a gynecological surgery indication (permanent contraception, benine surgery). The surgery is scheduled to take place during the luteal phase. Patients don't take a immunosuppressor, antibiotic or present inflammatory bowel disease, recent infection, pregnancy

Procedure: surgery (any volume) and / or pharmaceuticals treatment initiated or planned or only dynamic observation, in accordance with current clinical guidelines; Biological: Blood test; Biological: Stool samples

Interventions

surgery (any volume) and / or pharmaceuticals treatment initiated or planned or only dynamic observation, in accordance with current clinical guidelines PROCEDURE

The surgery is performed on both arms as part of the current / recommended treatment. But during this surgery, an extension of the samples is performed. In both arms, the surgeons take samples of the endometrium, peritoneum and peritoneal lavage. For patients with endometriosis, the lesion is also sampled.

Control group; Endometriosis group

Blood test BIOLOGICAL

Before surgery, the patient will need a blood test at the recommendation of the anaesthetist. This allows us to see the level of oestrogen and progesterone in the blood.

Control group; Endometriosis group

Stool samples BIOLOGICAL

Before the surgery, the patient will take a stool sample.

Control group; Endometriosis group

Eligibility Criteria

• Age: 18 Years - 42 Years
• Gender Eligibility Details: As endometriosis only affects non-menopausal women, the study concerns women of childbearing age. As it's the inflammatory lesions of endometriosis we're interested in, we need young patients, so we're limiting the age range to 18 to 42.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women aged 18-42 years.
• Surgery scheduled during the luteal phase.
• Written informed consent provided.
• Women with confirmed endometriosis and a surgical indication (due to persistent symptoms despite medical treatment and/or risk of organ damage).
• Hormonal therapy discontinued at least one month prior to surgery.
• Absence of isolated ovarian endometrioma.
• \- Women requiring benign gynecological surgery with no clinical or intraoperative evidence of endometriosis.
• Presence of inflammatory bowel disease (Crohn's disease, ulcerative colitis) or other autoimmune disorders (e.g., lupus, Sjögren's syndrome, antiphospholipid syndrome, rheumatoid arthritis, spondyloarthritis),
• Use of antibiotics within the month prior to surgery,
• Recent infection (\<2 weeks),
• Ongoing treatment with biologics or immunosuppressants,
• Contraindication to surgery due to general condition or comorbidities,
• Hormonal therapy within the month prior to surgery,
• Abdominopelvic surgery involving peritoneal breach within the previous 6 months,
• Pregnancy or breastfeeding,

You may not qualify if:

• Intraoperative impossibility to perform surgery due to local conditions with an unfavorable benefit-risk balance for the patient.
• Discovery of endometriosis during surgery in the control group.
• Antibiotic use in the month preceding the second stool sample (endometriosis group).

Sponsors & Collaborators

• University Hospital, Grenoble: lead
• Etablissement Français du Sang: collaborator

Study Sites (1)

CHUGA

Grenoble, Isère, 38000, France

Location

MeSH Terms

Conditions

Endometriosis

Interventions

Surgical Procedures, Operative; Hematologic Tests

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Laurence Chaperot, PhD

  Etablissement Français du Sang

  STUDY DIRECTOR

• Thierry Michy, Dortor

  Centre Universitaire Grenoble Alpes

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexandre Buisson, Doctor

CONTACT

+33679825389; abuisson2@chu-grenoble.fr

Lora Pejot, ARC

CONTACT

+33476766561; lpejot@chu-grenoble.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is a monocentric (at Grenoble University Hospital), open-label, prospective experimental study with a control arm. Given the extent of the biopsies performed during surgery, which exceed standard care, French legislation classifies this study as a Class 2 interventional study. Women in the endometriosis group will undergo collection during surgery with endometriotic lesions, adjacent tissue, eutopic endometrium, and peritoneal lavage during surgery. Controls will provide biopsies of eutopic endometrium, unaffected peritoneum, and peritoneal lavage during the gynecology surgery. For both groups, peripheral blood samples will be collected during routine care and stool samples obtained. For the endometriosis group, a second stool sample will be collected at 12 months. A clinical evaluation will be performed at inclusion for all participants and repeated at one year for the endometriosis group. Participation for control group subjects is limited to the day of surgery.

Study Record Dates

• First Submitted: July 11, 2025
• First Posted: July 22, 2025
• Study Start: September 9, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2027
• Last Updated: September 2, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

FR (1)