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

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).

Study Overview

• Status: Recruiting
• Conditions: Splenectomy
• Intervention / Treatment: Other: Spleen, blood and plasma collection

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.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Pierre Buffet, MD, PhD; Email: pierre.buffet@aphp.fr
• Study Contact Backup: Name: Hélène Morel; Phone Number: +33 1 71 49 63 46; Email: helene.morel@aphp.fr

Study Locations

• France
  • Clichy, France, 92110
    • Recruiting
    • Hopital Beaujon
    • Contact: Alain Sauvanet, MD, PhD; Phone Number: + 33 1 40 87 55 84; Email: alain.sauvanet@aphp.fr
    • Contact: Safi Dokmak; Phone Number: + 33 1 40 87 57 97; Email: safi.dokmak@aphp.fr
  • Paris, France, 75015
    • Recruiting
    • Hopital Necker-Enfants Malades
    • Contact: Pierre Buffet, MD, PhD; Email: pierre.buffet@aphp.fr
  • Paris, France, 75013
    • Recruiting
    • Hopital Pitie Salpetriere
    • Contact: Christophe Trésallet, MD, PhD; Phone Number: + 33 1 42 17 66 03; Email: christophe.tresallet@aphp.fr
  • Paris, France, 75012
    • Recruiting
    • Hopital Saint Antoine
    • Contact: François Paye, MD, PhD; Phone Number: + 33 1 49 28 25 61; Email: françois.paye@aphp.fr
  • Paris, France, 75015
    • Active, not recruiting
    • Institut Pasteur

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients; Adult patients 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.

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Exploring the genetic control of spleen function	Genetic control of spleen function.	Day 0
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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Institut Pasteur
• Investigators: Principal Investigator: Pierre Buffet, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2016
• Primary Completion (Estimated): October 16, 2031
• Study Completion (Estimated): October 16, 2031

Study Registration Dates

• First Submitted: May 13, 2024
• First Submitted That Met QC Criteria: May 13, 2024
• First Posted (Actual): May 17, 2024

Study Record Updates

• Last Update Posted (Actual): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 13, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Malaria; Blood; Sickle cell disease; Lymphocytes; Leukocytes; Erythrocytes; Spleen; Hereditary spherocytosis; Human splenic physiology; Splenic clearance; Splenic filtration mechanisms; Perfusion experiments; Role of the spleen in the adaptive immune response; Genetic spleen mechanisms
• Other Study ID Numbers: NI17003; 2024-A00654-43 (Other Identifier: IDRCB Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No