Clinical trial NCT06418256: Physiology and Pathologies Linked to Human Splenic Function : Direct and Ex-vivo Perfusion Explorations
Official title: Physiology and Pathologies Linked to Human Splenic Function : Direct and Ex-vivo Perfusion Explorations
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Splenectomy
Keywords: Spleen
Human splenic physiology
Splenic clearance
Splenic filtration mechanisms
Perfusion experiments
Role of the spleen in the adaptive immune response
Genetic spleen mechanisms
Blood
Erythrocytes
Leukocytes
Lymphocytes
Malaria
Sickle cell disease
Hereditary spherocytosis
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Institut Pasteur
First posted: 2024-05-17
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients with no age limit cared in one of the APHP hospital (Necker-Enfants Malades Hospital, Saint-Antoine Hospital, Pitié Salpêtrière Hospital and Beaujon Hospital) for whom a splenic intervention (spleno-pancreectomy, or a total or partial splenectomy) is planned as part of their treatment.

Brief summary: Human splenic physiology remains poorly understood due to lack of functional exploration. However, through its ability to recognize alterations or modifications in circulating cells and to trigger an innate and adaptive response in response to these anomalies, the spleen plays a central role in several diseases affecting blood cells, directly or indirectly. The analysis of the splenic clearance of abnormal cells during ex-vivo perfusions made it possible to clarify the pathogenesis of malaria and the role of the spleen in the adaptive immune response. The study's investigative team wishes to extend these explorations to other human diseases in which the spleen is involved, and to evaluate the preventive or curative potential of substances that can modify the perception of blood cells by the spleen (e.g. monoclonal antibodies directed against circulating cells, among other options).

Detailed description: Human splenic physiology remains poorly understood due to lack of functional exploration. However, through its ability to recognize alterations or modifications in circulating cells and to trigger an innate and adaptive response in response to these anomalies, the spleen plays a central role in several diseases affecting blood cells, directly or indirectly. The analysis of the splenic clearance of abnormal cells during ex-vivo perfusions made it possible to clarify the pathogenesis of malaria and the role of the spleen in the adaptive immune response. The study's investigative team wishes to extend these explorations to other human diseases in which the spleen is involved, and to evaluate the preventive or curative potential of substances that can modify the perception of blood cells by the spleen (e.g. monoclonal antibodies directed against circulating cells, among other options).

Participation to the study will be proposed to adult patients in whom a splenic intervention (spleno-pancreatectomy, or a total or partial splenectomy) is planned as part of their treatment.

One or more tubes of venous blood collected for the care will be retrieved following the pre- or intra-operative assessment. These samples will serve as controls during analyzes of splenic filtration mechanisms and/or perfusion experiments with populations of altered or modified cells and/or immunological and/or genetic analyses. Immediately following surgery, after careful examination by the pathologist in charge, the whole spleen or spleen fragments will be collected for further analysis. Whenever possible a catheter will be introduced in the splenic artery, the spleen will be flushed/rinsed with 0.1 - 2 L of cold perfusion medium then transferred to the laboratory for ex-vivo perfusion. Samples from different experimental conditions (for example red blood cell containing malaria parasite for a culture) may be introduced in the perfusion system pour kinetic analyses. Before and at the end of the ex-vivo perfusion, splenic blood and spleen fragments will be collected and processed for further analyses by cytology, cytometry, histology, immunohistochemistry, electronic microscopy, biochemistry, molecular biology, single cell analyses, on any other method. Peripheral and splenic blood samples or cells, as well as spleen fragments will be stored in. a biobank for further use or experimental analyses.

Eligibility criteria: Inclusion Criteria:

* Adult patients
* Patient requiring left splenopancreectomy or planned splenectomy regardless of the method or indication

Exclusion Criteria:

- The patient notified his doctor of his refusal to recover his spleen and blood volume

Primary outcomes:
measure: Refine the understanding of spleen role during infections and conditions of the red blood cell and other human blood cells
timeFrame: Day 0
Secondary outcomes:
measure: Exploring splenic immunological mechanisms
timeFrame: Day 0
measure: Kinetics of splenic clearance of altered or modified circulating elements
timeFrame: Day 0
measure: Exploring splenic clearance mechanisms
timeFrame: Day 0
measure: Exploring the genetic control of spleen function
timeFrame: Day 0
measure: Explore the impact of preservation processes on organ and cell functions, as well as engraftment
timeFrame: Day 0
Other outcomes:
Locations:
city: Clichy
country: France
facility: Hôpital Beaujon
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Paris
country: France
facility: Hôpital Pitié Salpêtrière
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
city: Paris
country: France
facility: Institut Pasteur
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Pierre Buffet, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: