An observational study in Immunosuppression and Kidney Transplantation, sponsored by Northwestern University. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2013-08-28.
Sponsored by Northwestern University · Observational
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.
Northwestern University is the lead sponsor of 1,396 studies on the registry; 199 are open to participants now.
Of its 102 completed or terminated interventional studies of FDA-regulated products, 73 (72%) have results posted.
Counted across the registry records on this site, refreshed daily.
Six to Twelve preoperative renal transplant living donor pairs.
Exclusion Criteria:
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.
Time frame: 3 months
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)
| Milestone | Participants |
|---|---|
| Started | 12 |
| Completed | 10 |
| Not completed | 2 |
| Withdrew: Physician decision | 2 |
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.
| Percentage of Control Cells | MLRs in the Presence of TAC | MLRs in the Presence of SRL |
|---|---|---|
| Cell Levels in 0.05-0.2 ng/mL TAC or SRL | 90 ± 20 | 85 ± 5 |
| Cell Levels in 0.3-3 ng/mL TAC or SRL | 25 ± 15 | 50 ± 10 |
| Cell Levels in > 5 ng/mL TAC or SRL | 10 ± 5 | 45 ± 10 |
Non-serious events are listed at a 1% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| All Participants | — | 0/12 (0%) | 0/12 (0%) |
| Age, Categorical(Participants) | All Participants |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 10 |
| >=65 years | 2 |
| Age Continuous(years) | All Participants |
|---|---|
| Mean | 47.08 ± 10.5 |
| Sex: Female, Male(Participants) | All Participants |
|---|---|
| Female | 6 |
| Male | 6 |
| Region of Enrollment(participants) | All Participants |
|---|---|
| United States | 12 |
This study is completed, as verified in May 2013. You cannot join it, but the record below documents what was studied.
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Northwestern University