Clinical trial NCT01230502
Conditions: Liver Transplant
Keywords: immunosuppression anti-rejection immune tolerance
Sponsor: University of Wisconsin, Madison
Start date: 2011-11-01; Completion date: 2012-06-01
Enrollment: 11 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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.

Detailed description:
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.

Arms: arm 1: Subjects who test Donor Specific Regulation (DSR) negative will not be randomized to possible tacrolimus withdrawal, and will remain on standard of care immunosuppression. arm 2: Subjects that are Donor Specific Regulation (DSR) positive and randomized (1:1) to Group 2 will remain on standard of care immunosuppression. arm 3: 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
Interventions: intervention 1: Group 1 Donor Specific Regulation (DSR) +, Mycophenolic acid (MPA) monotherapy intervention 2: data and sample collection intervention 3: data and sample collection
Intervention descriptions: intervention 1: 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. intervention 2: 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 intervention 3: 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.

Protocol documents: