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| ID | Type | Description | Link |
|---|---|---|---|
| CERL080AUS80T | Other Grant/Funding Number | Novartis Pharmaceuticals |
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insufficient study population to meet study objective
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| Name | Class |
|---|---|
| Novartis Pharmaceuticals | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 3: Donor Specific Regulation (DSR) -, standard of care | Active Comparator | Subjects who test Donor Specific Regulation (DSR) negative will not be randomized to possible tacrolimus withdrawal, and will remain on standard of care immunosuppression. |
|
| Group 2 Donor Specific Regulation (DSR) +; standard of care | Active Comparator | Subjects that are Donor Specific Regulation (DSR) positive and randomized (1:1) to Group 2 will remain on standard of care immunosuppression. |
|
| Group 1 Donor Specific Regulation (DSR) +, MPA monotherapy | Experimental | 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 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Group 1 Donor Specific Regulation (DSR) +, Mycophenolic acid (MPA) monotherapy | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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 | 12 months post enrollment/randomization |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Will Burlingham, PhD | University of Wisconsin, Madison | Principal Investigator |
| Anthony D'Alessandro, MD | University of Wisconsin, Madison | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Wisconsin- Madison | Madison | Wisconsin | 53792 | United States |
11 participants consented and were enrolled in the study. However, 2 of the subjects screen failed and did not participate in the study beyond providing their consent to participate. Thus only 9 subjects consented to and "started" the study and these 9 subjects are analyzed in the results.
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| ID | Title | Description |
|---|---|---|
| FG000 | Group 3: Donor Specific Regulation (DSR) -, Standard of Care | Subjects who test Donor specific regulation (DSR) negative will not be randomized to possible tacrolimus withdrawal, and will remain on standard of care immunosuppression. data and sample collection: Group 3 : 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. |
| FG001 | Group 2 Donor Specific Regulation (DSR) +; Standard of Care | Subjects that are DSR (donor specific regulation) positive and randomized (1:1)to Group 2 will remain on standard of care immunosuppression. data and sample collection: Group 2 : 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 |
| FG002 | Group 1 Donor Specific Regulation (DSR) +, 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 Withdrawal of Tacrolimus to mycophenolate monotherapy: Group 1: 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Group 3: Donor Specific Regulation DSR -, Standard of Care | Subjects who test DSR (donor specific regulation) negative will not be randomized to possible tacrolimus withdrawal, and will remain on standard of care immunosuppression. data and sample collection: Group 3 : 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | 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 | Posted | Mean | Standard Deviation | mL/min/1.73 sqm | 6 months post enrollment/randomization |
|
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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 | Group 3: DSR (Donor Specific Regulation) (-), Standard of Care | Subjects who test Donor specific regulation (DSR) negative will not be randomized to possible tacrolimus withdrawal, and will remain on standard of care immunosuppression. data and sample collection: Group 3 : 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 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Professor William Burlingham, PhD | University of Wisconsin | (608) 263-0119 | BURLINGHAM@SURGERY.WISC.EDU |
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| ID | Term |
|---|---|
| D009173 | Mycophenolic Acid |
| D013048 | Specimen Handling |
| ID | Term |
|---|---|
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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|
|
| data and sample collection | Other | 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 |
|
| data and sample collection | Other | 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. |
|
| BG001 | Group 2 Donor Specific Regulation DSR +; Standard of Care | Subjects that are DSR (donor specific regulation) positive and randomized (1:1)to Group 2 will remain on standard of care immunosuppression. data and sample collection: Group 2 : 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 |
| BG002 | Group 1 Donor Specific Regulation (DSR) +, MPA Monotherapy | Subjects that are DSR (donor specific regulation) 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 Withdrawal of Tacrolimus to mycophenolate monotherapy: Group 1: 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. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Age, Categorical | Number | participants |
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| Gender | Number | participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Group 2 DSR (+); Standard of Care | Subjects that are DSR positive and randomized (1:1)to Group 2 will remain on standard of care immunosuppression. data and sample collection: Group 2 : 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 |
| OG002 | Group 1 DSR (+), Withdrawal of Tacrolimus to MPA Monotherapy | Subjects that are 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 Withdrawal of Tacrolimus to mycophenolate monotherapy: Group 1: 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. |
|
|
| Primary | 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 | Posted | Mean | Standard Deviation | mL/min/1.73 sqm | 12 months post enrollment/randomization |
|
|
|
| 0 |
| 9 |
| 0 |
| 9 |
| EG001 | Group 2 DSR (Donor Specific Regulation) (+); Standard of Care | Subjects that are Donor specific regulation (DSR) positive and randomized (1:1)to Group 2 will remain on standard of care immunosuppression. data and sample collection: Group 2 : 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 | 0 | 0 | 0 | 0 |
| EG002 | Group 1 DSR (Donor Specific Regulation) (+),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 Withdrawal of Tacrolimus to mycophenolate monotherapy: Group 1: 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. | 0 | 0 | 0 | 0 |
The PI, or his designee, must notify the sponsor at least (10) days, if possible, or as soon as possible, prior to submitting this information.
| D005227 |
| Fatty Acids |
| D008055 | Lipids |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D008919 | Investigative Techniques |