An interventional study of Group 1 Donor Specific Regulation (DSR) +, Mycophenolic acid (MPA) monotherapy and data and sample collection in Liver Transplant, sponsored by University of Wisconsin, Madison. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-05-07.
Sponsored by University of Wisconsin, Madison · Not applicable, Interventional, and Treatment
To determine whether long-term maintenance therapy with a single drug (Myfortic) applied using advanced immunologic monitoring tools in selected patients can lead to superior native kidney function at 2 years without resulting in increased acute rejection episodes or deterioration of liver allograft function.
The hypothesis to be tested is that donor-microchimerism in specific cell populations promotes the development of donor-specific regulation which in turn allows for long-term maintenance therapy with a single drug (Myfortic) in selected patients leading to superior long-term outcomes. Subjects will be enrolled post-transplantation and will be liver transplant recipients who meet the eligibility and exclusion criteria. We will use post-transplant monitoring for donor-specific immunologic regulation (DSR+/ DSA negative) to direct the withdrawal of patients to Myfortic monotherapy. Donor microchimerism, DSR, DSA development will be performed on samples obtained every six months from patients on study. The ultimate objective of the study is to use immunologic monitoring to develop a rational approach to achieving individualized immunosuppression for liver transplant patients.
University of Wisconsin, Madison is the lead sponsor of 1,161 studies on the registry; 182 are open to participants now.
Of its 151 completed or terminated interventional studies of FDA-regulated products, 114 (75%) have results posted.
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Exclusion Criteria:
Subjects who test Donor Specific Regulation (DSR) negative will not be randomized to possible tacrolimus withdrawal, and will remain on standard of care immunosuppression.
Other: data and sample collection
Subjects that are Donor Specific Regulation (DSR) positive and randomized (1:1) to Group 2 will remain on standard of care immunosuppression.
Other: data and sample collection
Group 1 Donor Specific Regulation (DSR) +, Mycophenolic acid (MPA) monotherapy: Subjects that are Donor Specific Regulation (DSR) positive and randomized (1:1) to Group 1 will begin a taper off tacrolimus for 6 months, after repeat DSR testing at 6 months subject will either discontinue tacrolimus if they remain DSR negative or remain at reduced dose if converted to DSR positive
Drug: Group 1 Donor Specific Regulation (DSR) +, Mycophenolic acid (MPA) monotherapy
Group 1 Donor Specific Regulation (DSR) +, MPA monotherapy Mycophenolate sodium : Myfortic therapy will be maintained at a target dose of 720mg BID. Tacrolimus doses will be lowered to achieve levels of 3-5 ng/ml. 6 months later, immunological monitoring will be repeated and tacrolimus will be completely discontinued if the subject remains DSR + without development of donor specific antibodies (DSA). Those who become DSR- or develop DSA will remain on a tacrolimus dose achieving levels of 3-5 ng/ml, and will not undergone any additional reduction. Subjects will be followed for 24 months at 6 month intervals, and will provide health information and blood samples.
Also known as: Myfortic
Group 2 : Donor specific regulation (DSR) + standard of care: These subjects will be maintained on standard of care immunosuppression consisting of Tacrolimus and Mycophenolate sodium (MPS) with no reduction in tacrolimus dose during the 24 months of study enrollment. Subjects will be followed for 24 months at 6 month intervals, and will provide health information and blood samples
Group 3 : Donor specific regulation (DSR) - standard of care: These subjects are those who were DSR negative and/or DSA positive at enrollment and therefore are not eligible for the withdrawal aspect of the study. These subjects will be maintained on standard of care immunosuppression consisting of Tacrolimus and Mycophenolate sodium (MPS) with no reduction in tacrolimus dose during the 24 months of study enrollment. These subjects will be asked to provide heath information and donate blood, exclusively for research testing, at the same 6 month intervals as those in the other two arms of the study, and will be followed for 24 months.
Modification of Diet in Renal Disease (MDRD) Estimation of Glomerular Filtration Rate (GFR)
This outcome measure is used to determine if the reduction of calcineurin inhibitor immunosuppression leads to improved native kidney function. Native kidney function is assessed using the Modification of Diet in Renal Disease (MDRD) estimation of glomerular filtration rate (GFR) from serum or plasma creatinine samples at the reported time points. Reference intervals include: Healthy 18 years and up: 60-120 mL/min/1.73 sqm Chronic kidney disease: GFR \< 60 mL/min/1.73 sqm Kidney failure: GFR \< 15 mL/min/1.73 sqm
Time frame: 6 months post enrollment/randomization
Modification of Diet in Renal Disease (MDRD) Estimation of Glomerular Filtration Rate (GFR)
This outcome measure is used to determine if the reduction of calcineurin inhibitor immunosuppression leads to improved native kidney function. Native kidney function is assessed using the Modification of Diet in Renal Disease (MDRD) estimation of glomerular filtration rate (GFR) from serum or plasma creatinine samples at the reported time points. Reference intervals include: Healthy 18 years and up: 60-120 mL/min/1.73 sqm Chronic kidney disease: GFR \< 60 mL/min/1.73 sqm Kidney failure: GFR \< 15 mL/min/1.73 sqm
Time frame: 12 months post enrollment/randomization
| Milestone | Group 3: Donor Specific Regulation (DSR) -, Standard of Care | Group 2 Donor Specific Regulation (DSR) +; Standard of Care | Group 1 Donor Specific Regulation (DSR) +, MPA Monotherapy |
|---|---|---|---|
| Started | 9 | 0 | 0 |
| Completed | 9 | 0 | 0 |
| Not completed | 0 | 0 | 0 |
This outcome measure is used to determine if the reduction of calcineurin inhibitor immunosuppression leads to improved native kidney function. Native kidney function is assessed using the Modification of Diet in Renal Disease (MDRD) estimation of glomerular filtration rate (GFR) from serum or plasma creatinine samples at the reported time points. Reference intervals include: Healthy 18 years and up: 60-120 mL/min/1.73 sqm Chronic kidney disease: GFR \< 60 mL/min/1.73 sqm Kidney failure: GFR \< 15 mL/min/1.73 sqm
| mL/min/1.73 sqm | Group 3: DSR (-), Standard of Care | Group 2 DSR (+); Standard of Care | Group 1 DSR (+), Withdrawal of Tacrolimus to MPA Monotherapy |
|---|---|---|---|
| Modification of Diet in Renal Disease (MDRD) Estimation of Glomerular Filtration Rate (GFR) | 60.14 ± 16.39 | — | — |
This outcome measure is used to determine if the reduction of calcineurin inhibitor immunosuppression leads to improved native kidney function. Native kidney function is assessed using the Modification of Diet in Renal Disease (MDRD) estimation of glomerular filtration rate (GFR) from serum or plasma creatinine samples at the reported time points. Reference intervals include: Healthy 18 years and up: 60-120 mL/min/1.73 sqm Chronic kidney disease: GFR \< 60 mL/min/1.73 sqm Kidney failure: GFR \< 15 mL/min/1.73 sqm
| mL/min/1.73 sqm | Group 3: Donor Specific Regulation (DSR) -, Standard of Care | Group 2 Donor Specific Regulation (DSR) +; Standard of Care | Group 1 Donor Specific Regulation (DSR) +, MPA Monotherapy |
|---|---|---|---|
| Modification of Diet in Renal Disease (MDRD) Estimation of Glomerular Filtration Rate (GFR) | 82.4 ± 28.34 | — | — |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Group 3: DSR (Donor Specific Regulation) (-), Standard of Care | — | 0/9 (0%) | 0/9 (0%) |
| Group 2 DSR (Donor Specific Regulation) (+); Standard of Care | — | — | — |
| Group 1 DSR (Donor Specific Regulation) (+),MPA Monotherapy | — | — | — |
| Age, Continuous(years) | Group 3: Donor Specific Regulation DSR -, Standard of Care | Group 2 Donor Specific Regulation DSR +; Standard of Care | Group 1 Donor Specific Regulation (DSR) +, MPA Monotherapy | Total |
|---|---|---|---|---|
| Mean | 51 ± 14.757 | — | — | 51 ± 14.76 |
| Age, Categorical(participants) | Group 3: Donor Specific Regulation DSR -, Standard of Care | Group 2 Donor Specific Regulation DSR +; Standard of Care | Group 1 Donor Specific Regulation (DSR) +, MPA Monotherapy | Total |
|---|---|---|---|---|
| <=18 years | 0 | — | — | 0 |
| Between 18 and 65 years | 8 | — | — | 8 |
| >=65 years | 1 | — | — | 1 |
| Gender(participants) | Group 3: Donor Specific Regulation DSR -, Standard of Care | Group 2 Donor Specific Regulation DSR +; Standard of Care | Group 1 Donor Specific Regulation (DSR) +, MPA Monotherapy | Total |
|---|---|---|---|---|
| Female | 3 | — | — | 3 |
| Male | 6 | — | — | 6 |
| Region of Enrollment(participants) | Group 3: Donor Specific Regulation DSR -, Standard of Care | Group 2 Donor Specific Regulation DSR +; Standard of Care | Group 1 Donor Specific Regulation (DSR) +, MPA Monotherapy | Total |
|---|---|---|---|---|
| United States | 9 | — | — | 9 |
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University of Wisconsin, Madison