Physiology and Pathologies Linked to Human Splenic Function : Direct and Ex-vivo Perfusion Explorations

Splenectomy Clinical Trial

— SPLEENVIVO  

Official title:

Physiology and Pathologies Linked to Human Splenic Function : Direct and Ex-vivo Perfusion Explorations

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06418256
• Other study ID #: NI17003
• Secondary ID: 2024-A00654-43
• Status: Recruiting
• Start date: October 16, 2016
• Est. completion date: October 16, 2031

Study information

• Verified date: May 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Pierre Buffet, MD, PhD
• Email: pierre.buffet[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: October 16, 2031
• Est. primary completion date: October 16, 2031
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Splenectomy

Intervention

Other:
• Spleen, blood and plasma collection
Adult patients for whom a splenic intervention (spleno-pancreectomy, or a total or partial splenectomy) is planned as part of their care. One or more tubes of venous blood collected for the care will be recovered following the pre- or intra-operative assessment. 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. Before and at the end of the ex-vivo perfusion, splenic blood and spleen fragments will be collected and processed for further analyses.

Locations

Country	Name	City	State
France	Hôpital Beaujon	Clichy
France	Hôpital Necker-Enfants Malades	Paris
France	Hôpital Pitié Salpêtrière	Paris
France	Hôpital Saint Antoine	Paris
France	Institut Pasteur	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Institut Pasteur

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Refine the understanding of spleen role during infections and conditions of the red blood cell and other human blood cells	Ability of the isolated-perfused human spleen to filter altered cell populations.	Day 0
Secondary	Exploring splenic immunological mechanisms	Explore splenic immunological mechanisms including the maintenance of long-term memory against Plasmodium sp antigens. and other infectious agents: Bartonella sp., Babesia sp., smallpox virus, measles, hepatitis.	Day 0
Secondary	Kinetics of splenic clearance of altered or modified circulating elements	Explore the spleen filter role during infections, illnesses or use of blood cells, including properties of cells retained in the spleen, possibily after modification in vitro.	Day 0
Secondary	Exploring splenic clearance mechanisms	Clearance mechanisms: tissue and cellular topography and concentration of deposition of normal or altered or modified cells in the spleen (Histology, Imaging, Electron Microscopy, etc.).	Day 0
Secondary	Exploring the genetic control of spleen function	Genetic control of spleen function.	Day 0
Secondary	Explore the impact of preservation processes on organ and cell functions, as well as engraftment	Testing optimized freezing methods with evaluation of cell function in vitro and engraftment in a mouse model.	Day 0