Liver TransplantNCT01230502
Mycophenolic Acid (MPA) Monotherapy in Liver Transplantation
A study testing Group 1 Donor Specific Regulation (DSR) +, Mycophenolic acid (MPA) monotherapy and data and sample collection in people with Liver Transplant, run by University of Wisconsin, Madison at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Transplant
- What is being tested?
- Group 1 Donor Specific Regulation (DSR) +, Mycophenolic acid (MPA) monotherapy and data and sample collection
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2011to Jun 2012
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subjects, ages 18 years and older who have received a primary liver transplant from a deceased donor for end stage liver disease *(ESLD).
- Women of child-bearing potential must have a negative serum pregnancy test at the time of screening and agree to use a medically acceptable method of contraception throughout the study and for 3 months following discontinuation of study treatment.
Who cannot join
- Recipients of multi-organ transplants.
- Recipients with positive crossmatch with their donor (current or previously).
- Subjects with a screening white blood cell count ≤ 2,000 mm3 or absolute neutrophil count (ANC) ≤ 1000, platelet count ≤ 100,000 mm3.
- Recipients with a hematocrit < 32.
- History of malignancy within 5 years of enrollment (except for adequately treated basal cell or squamous cell carcinoma of the skin).
- Subjects who are positive for hepatitis C, hepatitis B surface antigen, or HIV.
Show all 19Show fewer
- Subjects with previous intolerance to full dose MPA agent.
- Subjects with a history of acute rejection within 6 months prior to study enrollment.
- Subjects who have had chronic ductopenic rejection.
- Subjects who had rejection in the first-year post-transplant and are less than 3 years post-transplant.
- Subjects who had rejection requiring treatment with thymoglobulin or Orthoclone-OKT3 (OKT3) at anytime post-transplant.
- Original cause of ESLD related to autoimmune diseases such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis.
- Subjects who have received an investigational drug within 4 weeks of study entry.
- Subjects with a history of a psychological illness or condition such as to interfere with the subject's ability to understand the requirements of the study.
- Female subjects who are pregnant or nursing or females who are unwilling to use contraception during the study.
- Subjects who are currently receiving any therapy for immunosuppression other than a MPA agent and tacrolimus.
- Subjects with a history of hepatocellular carcinoma (T2 >).
- Subjects with severe coexisting disease or presenting with any unstable medical condition which could affect study objectives.
- Subjects who have a known hypersensitivity to tacrolimus or mycophenolate
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Wisconsin- Madison
Madison, Wisconsin, 53792
About this study
Official title: Donor Specific Regulation (DSR) Guided Tacrolimus Withdrawal to Myfortic Monotherapy in Liver Transplantation
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.
Read the 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.
- Conditions
- Liver Transplant
- Being tested
- Group 1 Donor Specific Regulation (DSR) +, Mycophenolic acid (MPA) monotherapy, data and sample collection
- Keywords
- immunosuppression, anti-rejection, immune tolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Group 1 Donor Specific Regulation (DSR) +, Mycophenolic acid (MPA) monotherapyDrug
Also called Myfortic
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.
data and sample collectionOther
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 collectionOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: data and sample collection |
| 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. Receives: Other: data and sample collection |
| 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 Receives: Drug: Group 1 Donor Specific Regulation (DSR) +, Mycophenolic acid (MPA) monotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 12 months post enrollment/randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2010 (estimated)
- Study startNov 2011
- Primary completionMay 2012
- Study completionJun 2012
Why it stopped: insufficient study population to meet study objective
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Liver TransplantStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Will Burlingham, PhD, Principal investigator, University of Wisconsin, MadisonAnthony D'Alessandro, MD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01230502
- Sponsor's protocol ID
- UW H-2010-0121
- Other IDs
- CERL080AUS80T
- Status last verified
- Apr 2014
- First submitted
- 27 Oct 2010
- Last updated
- 7 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Donor Specific Regulation (DSR) Guided Tacrolimus Withdrawal to Myfortic Monotherapy in Liver Transplantation
- ClinicalTrials.gov ID
- NCT01230502
- Acronym / sponsor ID
- UW H-2010-0121
- Conditions
- Liver Transplant
- Keywords
- immunosuppression, anti-rejection, immune tolerance
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: insufficient study population to meet study objective
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- Nov 2011
- Primary completion
- May 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 29 Oct 2010 (estimated)
- Results
- Posted 7 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 3: Donor Specific Regulation (DSR) -, standard of care | Active comparator | Other: data and sample collectionSubjects 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 | Other: data and sample collectionSubjects 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 | Drug: Group 1 Donor Specific Regulation (DSR) +, Mycophenolic acid (MPA) monotherapyGroup 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Male or female subjects, ages 18 years and older who have received a primary liver transplant from a deceased donor for end stage liver disease *(ESLD).
- Women of child-bearing potential must have a negative serum pregnancy test at the time of screening and agree to use a medically acceptable method of contraception throughout the study and for 3 months following discontinuation of study treatment.
Key exclusion criteria (19 listed)
- Recipients of multi-organ transplants.
- Recipients with positive crossmatch with their donor (current or previously).
- Subjects with a screening white blood cell count ≤ 2,000 mm3 or absolute neutrophil count (ANC) ≤ 1000, platelet count ≤ 100,000 mm3.
- Recipients with a hematocrit < 32.
- History of malignancy within 5 years of enrollment (except for adequately treated basal cell or squamous cell carcinoma of the skin).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Group 1 Donor Specific Regulation (DSR) +, Mycophenolic acid (MPA) monotherapyAlso: MyforticGroup 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. | Drug | Group 1 Donor Specific Regulation (DSR) +, MPA monotherapy |
| data and sample collectionGroup 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 | Other | Group 2 Donor Specific Regulation (DSR) +; standard of care |
| data and sample collectionGroup 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. | Other | Group 3: Donor Specific Regulation (DSR) -, standard of care |
Primary outcome
Modification of Diet in Renal Disease (MDRD) Estimation of Glomerular Filtration Rate (GFR)
Time frame: 6 months post enrollment/randomization
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
Modification of Diet in Renal Disease (MDRD) Estimation of Glomerular Filtration Rate (GFR)
Time frame: 12 months post enrollment/randomization
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Will Burlingham, PhD principal investigator
University of Wisconsin, Madison
Anthony D'Alessandro, MD principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Group 1 Donor Specific Regulation (DSR) +, Mycophenolic acid (MPA) monotherapy and data and sample collection in people with Liver Transplant, run by University of Wisconsin, Madison at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Modification of Diet in Renal Disease (MDRD) Estimation of Glomerular Filtration Rate (GFR) (time frame: 6 months post enrollment/randomization). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2014.