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| Name | Class |
|---|---|
| Astellas Pharma US, Inc. | INDUSTRY |
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The study is a laboratory investigation comparing the regulatory effects of different immunosuppressive therapies in an in vitro human MLR assay of selecting specific immunosuppressive therapy to promote a regulatory profile and determining possibly newer accepted dosing and drug concentrations for agents most associated with this regulatory profile.
Life-long immunosuppressive (IS) therapy is typically required in the great majority of organ transplants. Immunobiologically correct IS dosing, tapering to low levels and/or monotherapy could lower the incidence of complications related to IS and improve long term graft and patient survival. The current standard of IS care for liver transplant recipients are the calcineurin-inhibitors (CNIs) tacrolimus (TAC) and cyclosporine (CSA), although alternative IS drugs such as mycophenolate mofetil (MMF) and sirolimus (SRL) are available for use in select patients. This is also true for kidney, pancreas and heart transplant recipients, with TAC being favored in each case. The ideal IS agent is one that can be given at low levels such that both rejection and long term toxicity are minimized. Directly related to IS minimization might be the development of a regulatory, "tolerance profile", as assessed by ex vivo immunophenotyping and functional assays that might test these specific IS agents singly, in combination or even in sequence.
Human Tregs and DCregs can be more predominantly generated in the presence of one of three IS agents with different modes of action, i.e., TAC, MMF or SRL, and in different conditions of antigen presentation and alloimmune incompatibility.
This is a bench protocol studying the effects of TAC, MMF and SRL on pre operative living renal recipient donor pair.
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| Measure | Description | Time Frame |
|---|---|---|
| CD4+CD25 High FOXP3+ Cell Levels in Mixed Lymphocyte Reactions (MLRs) of Renal Pre-transplant Recipients/Donors | CD4+CD25 high FOXP3+ cell levels in mixed lymphocyte reactions (MLRs) of Renal Pre-transplant Recipients/Donors were measured in the presence of 1) No Drug/Control; 2) 0.05-0.2, 0.3-3 and > 5 ng/ml Tacrolimus (TAC); OR 3) 0.05-0.2, 0.3-3 and > 5 ng/ml Sirolimus (SRL). CD4+CD25 high FOXP3+ cell levels in the MLRs with TAC or SRL are expressed as the percentage of CD4+CD25 high FOXP3+ cell levels in the MLRs with no drug. | 3 months |
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Inclusion Criteria:
Exclusion Criteria:
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Six to Twelve preoperative renal transplant living donor pairs.
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| Name | Affiliation | Role |
|---|---|---|
| Lorenzo Gallon, MD | Northwestern University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northwestern Memorial Hospital | Chicago | Illinois | 60611 | United States |
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Recruit donor/recipient renal transplant subjects for blood draw before renal transplant surgery. Peripheral mononuclear cells (PBMC) were isolated from the blood, and were cultured in the following combinations: Recipient PMBC + Donor PBMC + No drug Recipient PMBC + Donor PBMC + Tacrolimus (TAC) Recipient PMBC + Donor PBMC + Sirolimus (SRL)
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| ID | Title | Description |
|---|---|---|
| FG000 | Participants | 12 participants were recruited/consented for the study. 2 subjects (donor/recipient pair) were withdrawn from the study. Ten participants (5 donors, 5 recipients) had blood drawn before renal transplant surgery. Peripheral mononuclear cells (PBMC) were isolated from the blood, and were cultured in the following combination: Recipient PMBC + Donor PBMC + Sirolimus (SRL) |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
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| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | All participants (6 donors, 6 recipients) had blood drawn before renal transplant surgery. Peripheral mononuclear cells (PBMC) were isolated from the blood, and were cultured in the following combination: Recipient PMBC + Donor PBMC + No drug Recipient PMBC + Donor PBMC + Tacrolimus (TAC) Recipient PMBC + Donor PBMC + Sirolimus (SRL) |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | CD4+CD25 High FOXP3+ Cell Levels in Mixed Lymphocyte Reactions (MLRs) of Renal Pre-transplant Recipients/Donors | CD4+CD25 high FOXP3+ cell levels in mixed lymphocyte reactions (MLRs) of Renal Pre-transplant Recipients/Donors were measured in the presence of 1) No Drug/Control; 2) 0.05-0.2, 0.3-3 and > 5 ng/ml Tacrolimus (TAC); OR 3) 0.05-0.2, 0.3-3 and > 5 ng/ml Sirolimus (SRL). CD4+CD25 high FOXP3+ cell levels in the MLRs with TAC or SRL are expressed as the percentage of CD4+CD25 high FOXP3+ cell levels in the MLRs with no drug. | For each arm, blood samples from 5 donor/recipient pairs (i.e., 10 participants) were used. | Posted | Mean | Standard Deviation | Percentage of Control Cells | 3 months |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | All Participants | All participants (6 donors, 6 recipients) had blood drawn before renal transplant surgery. Peripheral mononuclear cells (PBMC) were isolated from the blood, and were cultured in the following combination: Recipient PMBC + Donor PBMC + Sirolimus (SRL) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Lorenzo Gallon, MD - Study Principal Investigator | Northwestern University | 312-695-4457 | l-gallon@northwestern.edu |
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White Cells.
| Participants |
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| Age Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| OG001 | MLRs in the Presence of SRL | All participants (5 donors, 5 recipietns) had blood drawn before renal transplant surgery. Peripheral mononuclear cells (PBMC) were isolated from the blood, and were cultured in teh following combination: Recipient PMBC + Donor PBMC + Sirolimus (SRL) |
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| 0 |
| 12 |
| 0 |
| 12 |
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