Spleen Transplant in Solid Organ Transplantation

NCT ID: NCT04827186

Last Updated: 2024-02-13

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-26
• Study Completion Date: 2026-04-01

Brief Summary

Although the notions that kidney transplantation is the treatment of choice for patients with end-stage renal disease and that simultaneous kidney and pancreas transplant is the only treatment able to restore euglycemia in patients with type 1 diabetes and selected patients with type 2 diabetes, are now consolidated, rates of transplantation remain low among potential candidates with high levels of preformed anti-HLA antibodies. Most of the data comes from the experience in kidney transplant but can be easily translated to pancreas transplant.

Approximately 30% of patients on the transplant waiting list have evidence of sensitization in the form of alloantibodies, generated from exposure to previous transplants, blood transfusions, pregnancy, or other events. The presence of a panel-reactive antibody level of at least 80% (i.e. a high level of sensitization) creates difficulty in finding matched kidneys from compatible donors, leading to lower rates of transplantation in highly sensitized candidates compared to non-sensitized; the longer waiting times translates in an increased mortality rate. Despite the development of desensitization strategies and the advancement in immunosuppression protocols, it is apparent that transplanting these patients carries an increased risk of acute antibody mediated rejection; 25%-50% of transplants will have an early acute antibody mediated rejection . Most of these rejections can be successfully treated, but a high rate of transplant glomerulopathy and chronic antibody mediated rejection (AMR) leading to accelerated allograft failure is common.

Detailed Description

Although the notions that kidney transplantation is the treatment of choice for patients with end-stage renal disease and that simultaneous kidney and pancreas transplant is the only treatment able to restore euglycemia in patients with type 1 diabetes and selected patients with type 2 diabetes, are now consolidated, rates of transplantation remain low among potential candidates with high levels of preformed anti-HLA antibodies. Most of the data comes from the experience in kidney transplant but can be easily translated to pancreas transplant.

Approximately 30% of patients on the transplant waiting list have evidence of sensitization in the form of alloantibodies, generated from exposure to previous transplants, blood transfusions, pregnancy, or other events. The presence of a panel-reactive antibody level of at least 80% (i.e. a high level of sensitization) creates difficulty in finding matched kidneys from compatible donors, leading to lower rates of transplantation in highly sensitized candidates compared to non-sensitized; the longer waiting times translates in an increased mortality rate. Despite the development of desensitization strategies and the advancement in immunosuppression protocols, it is apparent that transplanting these patients carries an increased risk of acute antibody mediated rejection; 25%-50% of transplants will have an early acute antibody mediated rejection . Most of these rejections can be successfully treated, but a high rate of transplant glomerulopathy and chronic antibody mediated rejection (AMR) leading to accelerated allograft failure is common.

This protocol has been designed to demonstrate the feasibility and efficacy of spleen transplant as a desensitization strategy for highly sensitized patients, potential candidates of kidney or simultaneous kidney pancreas transplant with (positive cross-match by flow cytometry (T or B) or B positive standard cross-match). After obtaining surgical and research consent at a pre-transplant clinic visit, patients will be receiving spleen transplant followed by spleen removal and kidney or simultaneous kidney pancreas transplant. Duration of the subject participation will begin upon consent and will last for one year after the surgery.

Incidence of treated acute rejection (humoral or cellulo-mediated) within the first year (defined as biopsy proven or clinically indicated) will be determined. Graft and patient survival will be monitored and compared with a cohort of highly sensitized patients with similar immunological characteristics, treated with our standard protocol. DSA levels and post-transplant cross-match will be determined.

Conditions

Kidney Transplant Rejection; Positive FCXM (T or B Cell Positive); Positive CDC Cross-Match (B Cell Positive); Kidney/Pancreas Transplant Rejection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

highly sensitized patients with either a positive FCXM, or positive CDC cross-match

highly sensitized patients that receive a donor offer and have either a positive FCXM (T or B cell positive) or positive CDC cross-match (B cell positive); a positive CDC cross-match (T cell positive) remains a contraindication at this time.

Group Type: EXPERIMENTAL

Spleen Transplantation/Removal

Intervention Type: PROCEDURE

Spleen transplantation/removal and kidney transplantation alone or simultaneous kidney and pancreas transplantation in highly sensitized patients with either a positive flow cytometry cross-match (FCXM) (T or B cell positive) or a complement-dependent cytotoxicity (CDC) cross-match (B cell positive).

historical cohort of highly sensitized patients with a positive FCXM, or positive CDC cross-match

The control group, as comparison, will be an historical cohort of highly sensitized patients with positive flow (B and T) or positive B standard crossmatch, which received kidney transplant alone or simultaneous kidney and pancreas transplant and followed our standard protocol

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Spleen Transplantation/Removal

Spleen transplantation/removal and kidney transplantation alone or simultaneous kidney and pancreas transplantation in highly sensitized patients with either a positive flow cytometry cross-match (FCXM) (T or B cell positive) or a complement-dependent cytotoxicity (CDC) cross-match (B cell positive).

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Subjects must give written informed consent, and
• Subject is ≥ 18 years of age, and
• Subject is eligible for a kidney or simulateous kidney pancreas transplant, and
• Subjects are highly sensitized (cPRA 98-100%), and
• Subjects have a positive T flow crossmatch

Exclusion Criteria

• Severe cardiac disease not amenable to intervention
• Clinical significant systemic infection within 30 days prior to transplant
• Life expectancy < 1 Year
• Positive pregnancy test performed < 1 week prior to enrollment or intention to plan a pregnancy in the following year
• Current drug or alcohol abuse
• Uncontrolled, severe psychiatric illness
• Combined transplantation of kidney and other organs

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Illinois at Chicago

OTHER

Sponsor Role: lead

Responsible Party

Ivo G Tzvetanov

Chief of Transplantation & Associate Professor, Department of Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ivo Tzvetanov, MD

Role: PRINCIPAL_INVESTIGATOR

University of Illinois at Chicago

Locations

University of Illinois at Chicago

Chicago, Illinois, United States

Countries

United States

Other Identifiers

2021-0286

Identifier Type: -

Identifier Source: org_study_id