ImmunosuppressionLITMUSNCT02541916
Liver Immune Tolerance Marker Utilization Study
A study of Immunosuppression and Immune Tolerance, run by University of Toronto at 1 site in Canada.
Trial summary
The purpose of this study is to validate and test a tolerance gene expression profile for the identification of operationally tolerant liver transplant recipients, allowing for the successful withdrawal of immunosuppression without rejection in these patients. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Immunosuppression, Immune Tolerance
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 1 siteCanada
- Study dates
- Apr 2015to 31 May 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- To be eligible to participate in this study, patients must:
- Be between 18 and 65 years of age.
- Be recipients of a hepatic allograft.
- Be less than 3 months post-transplant and be experiencing rejection, or be a minimum of 3 months post-transplant with or without presently experiencing rejection.
- Be healthy live liver donors
Who cannot join
- Patients with the following conditions may not participate in the study:
- Patients under the age of 18 and over the age of 65.
- Patients who are positive for Human Immunodeficiency Virus (HIV),
- Patients who have detectable levels of HCV RNA, and HBV DNA, at the time of enrollment.
- Patients who have a combined transplant and/or have been re-transplanted.
- Patients taking immunosuppression for other diseases besides their liver transplant.
- Patients unable to give written informed consent in accordance with research ethics board guidelines.
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to validate and test a tolerance gene expression profile for the identification of operationally tolerant liver transplant recipients, allowing for the successful withdrawal of immunosuppression without rejection in these patients.
Read the detailed description
Previous pre-clinical work in the Levy Lab identified a novel biomarker gene set for the identification of tolerance in murine models of rapamycin-induced cardiac tolerance and spontaneous hepatic tolerance. Validation of this gene expression tolerance biomarker in operationally tolerant patients is now required for its implementation in the clinical setting. This proposal intends to validate and test our pre-clinically established tolerance gene expression biomarker in the clinical setting in order to translate our findings into improving the length and quality of life of transplant patients in the clinic.
The investigators hypothesize that a distinct gene expression profile expressed in the peripheral blood will identify operationally tolerant liver transplant recipients, allowing for the successful withdrawal of immunosuppression in these patients. Our study aims are: (I) To validate the pre-clinical gene expression profile for the identification of operationally tolerant liver recipients in plasma peripheral blood mononuclear cells (PBMCs) (2) To determine that the gene expression profile in the PBMCs is the same as the intra-graft gene expression profile (3) To demonstrate that liver transplant recipients with the tolerant gene expression profile can be safely weaned off of immunosuppression.
This proof of principle study will be conducted in two phases at the Toronto General Hospital (TGH) Phase 1 will address study aims 1 and 2, and phase 2 will address study aim 3. Potential participants will be screened and selected following predefined eligibility criteria. Eligible participants will undergo an informed consent process. The primary goal of this study is to validate the pre-clinical tolerant gene expression profile that will allow for the identification of tolerant liver recipients and for the monitored weaning off immunosuppression in these tolerant patients.
- Conditions
- Immunosuppression, Immune Tolerance
- Being tested
- Controlled weaning of immunosuppression
- Keywords
- Transplantation Tolerance, Immune Tolerance, Transplantation, Liver Transplantation, Biological Markers, Gene Expression, Immunosuppression, Immunology, Multiplex Polymerase Chain Reaction, Real-Time Polymerase Chain Reaction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Controlled weaning of immunosuppressionOther
At week 0 patients have liver biopsy and liver functional tests (LFTs). Week 1-4 medication reduction to 1.5mg Tacrolimus (Tac) daily or 150mg Cyclosporine A (CsA). At week 4 LFTs. Week 5-8 medication reduction to 1mg Tac / 100mg CsA. Week 8 LFTs. Week 9-12 reduction to 0.5mg Tac/ 50mg CsA. Week 12 LFTs. Week 13-16 reduction to 0mg. Week 16 liver biopsy \& LFTs. Weekly LFTs performed Week 17-20. Monthly LFTs for the next 3 months. LFTs every 3 months for monitoring.
| Study group | Role | What they receive |
|---|---|---|
| Controlled weaning of immunosuppression | Experimental | Participants who are found to have the tolerance gene expression profile during phase 1 of the study will undergo closely monitored immunosuppression weaning during phase 2. Receives: Other: Controlled weaning of immunosuppression |
What is being measured
The primary outcome is the main question the study is designed to answer.
Validation of Tolerance Gene Expression Profile
The primary endpoint of this study is the identification and validation of a unique tolerance gene expression profile, consisting of a 6 gene profile, in 3-6 operationally tolerant patients compared to 25 rejecting and 25 healthy controls.
Measured: Enrollment to one year post cessation of immunosuppression
Secondary outcomes (2)
Tolerance gene expression profile in graft versus peripheral blood mononuclear cells (PBMCs)
This endpoint will be defined as the ratio of patients (n=55) that will express the tolerance gene expression profile in the liver graft versus in the peripheral blood mononuclear cells.
Measured: Enrollment to one year post cessation of immunosuppression
Test of tolerance gene expression profile
This endpoint will assess whether the tolerance gene expression profile can be successfully used to select immunosuppressed patients for the successful weaning off immunosuppression. This endpoint will be evaluated using the number of successful immunosuppression-weaned patients from a 7-10 patient cohort. Successful immunosuppression-weaned patients are defined as patients who achieve an immunosuppression free state without any histological or clinical evidence of rejection for a minimum of 1 year.
Measured: Enrollment to one year post cessation of immunosuppression
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2015 (estimated)
- Study startApr 2015
- Primary completion31 May 2021
- Study completion31 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ImmunosuppressionStudies of the same condition, open and under way.
- 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
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gary A Levy, O. Ont. MD. FRCP AGAF, University of Toronto
- Investigators
- Gary Levy, M.D., Principal investigator, University Health Network, University of TorontoLeslie Lilly, M.D., Study chair, University Health Network, TorontoNazia Selzner, M.D. PhD., Study chair, University Health Network, TorontoMeaghan MacArthur, M.Ed, Study director, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02541916
- Sponsor's protocol ID
- Tol002
- Acronym
- LITMUS
- Status last verified
- Sep 2021
- First submitted
- 2 Sep 2015
- Last updated
- 30 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Chruscinski A, Rojas-Luengas V, Moshkelgosha S, Issachar A, Luo J, Yowanto H, Lilly L, Smith R, Renner E, Zhang J, Epstein M, Grant D, McEvoy CM, Konvalinka A, Humar A, Adeyi O, Fischer S, Volmer FH, Taubert R, Jaeckel E, Juvet S, Selzner N, Levy GA. Evaluation of a gene expression biomarker to identify operationally tolerant liver transplant recipients: the LITMUS trial. Clin Exp Immunol. 2022 Jan 28;207(1):123-139. doi: 10.1093/cei/uxab011.
PubMed 35020854
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Liver Immune Tolerance Marker Utilization Study
- ClinicalTrials.gov ID
- NCT02541916
- Acronym / sponsor ID
- LITMUS / Tol002
- Conditions
- Immunosuppression, Immune Tolerance
- Keywords
- Transplantation Tolerance, Immune Tolerance, Transplantation, Liver Transplantation, Biological Markers, Gene Expression, Immunosuppression, Immunology
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- University of TorontoUniversity, hospital or other
- Study start
- Apr 2015 (actual)
- Primary completion
- 31 May 2021 (actual)
- Study completion
- 31 May 2021 (actual)
- First posted
- 4 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to validate and test a tolerance gene expression profile for the identification of operationally tolerant liver transplant recipients, allowing for the successful withdrawal of immunosuppression without rejection in these patients.
Detailed description
Previous pre-clinical work in the Levy Lab identified a novel biomarker gene set for the identification of tolerance in murine models of rapamycin-induced cardiac tolerance and spontaneous hepatic tolerance. Validation of this gene expression tolerance biomarker in operationally tolerant patients is now required for its implementation in the clinical setting. This proposal intends to validate and test our pre-clinically established tolerance gene expression biomarker in the clinical setting in order to translate our findings into improving the length and quality of life of transplant patients in the clinic.
The investigators hypothesize that a distinct gene expression profile expressed in the peripheral blood will identify operationally tolerant liver transplant recipients, allowing for the successful withdrawal of immunosuppression in these patients. Our study aims are: (I) To validate the pre-clinical gene expression profile for the identification of operationally tolerant liver recipients in plasma peripheral blood mononuclear cells (PBMCs) (2) To determine that the gene expression profile in the PBMCs is the same as the intra-graft gene expression profile (3) To demonstrate that liver transplant recipients with the tolerant gene expression profile can be safely weaned off of immunosuppression.
This proof of principle study will be conducted in two phases at the Toronto General Hospital (TGH) Phase 1 will address study aims 1 and 2, and phase 2 will address study aim 3. Potential participants will be screened and selected following predefined eligibility criteria. Eligible participants will undergo an informed consent process. The primary goal of this study is to validate the pre-clinical tolerant gene expression profile that will allow for the identification of tolerant liver recipients and for the monitored weaning off immunosuppression in these tolerant patients.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Controlled weaning of immunosuppression | Experimental | Other: Controlled weaning of immunosuppressionParticipants who are found to have the tolerance gene expression profile during phase 1 of the study will undergo closely monitored immunosuppression weaning during phase 2. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- To be eligible to participate in this study, patients must:
Key exclusion criteria (7 listed)
- Patients with the following conditions may not participate in the study:
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 |
|---|---|---|
| Controlled weaning of immunosuppressionAt week 0 patients have liver biopsy and liver functional tests (LFTs). Week 1-4 medication reduction to 1.5mg Tacrolimus (Tac) daily or 150mg Cyclosporine A (CsA). At week 4 LFTs. Week 5-8 medication reduction to 1mg Tac / 100mg CsA. Week 8 LFTs. Week 9-12 reduction to 0.5mg Tac/ 50mg CsA. Week 12 LFTs. Week 13-16 reduction to 0mg. Week 16 liver biopsy \& LFTs. Weekly LFTs performed Week 17-20. Monthly LFTs for the next 3 months. LFTs every 3 months for monitoring. | Other | Controlled weaning of immunosuppression |
Primary outcome
Validation of Tolerance Gene Expression Profile
Time frame: Enrollment to one year post cessation of immunosuppression
The primary endpoint of this study is the identification and validation of a unique tolerance gene expression profile, consisting of a 6 gene profile, in 3-6 operationally tolerant patients compared to 25 rejecting and 25 healthy controls.
2 secondary outcomes
Tolerance gene expression profile in graft versus peripheral blood mononuclear cells (PBMCs)
Time frame: Enrollment to one year post cessation of immunosuppression
Test of tolerance gene expression profile
Time frame: Enrollment to one year post cessation of immunosuppression
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2021.
- Derived from this study: PubMed 35020854Chruscinski A, Rojas-Luengas V, Moshkelgosha S, Issachar A, Luo J, Yowanto H, Lilly L, Smith R, Renner E, Zhang J, Epstein M, Grant D, McEvoy CM, Konvalinka A, Humar A, Adeyi O, Fischer S, Volmer FH, Taubert R, Jaeckel E, Juvet S, Selzner N, Levy GA. Evaluation of a gene expression biomarker to identify operationally tolerant liver transplant recipients: the LITMUS trial. Clin Exp Immunol. 2022 Jan 28;207(1):123-139. doi: 10.1093/cei/uxab011.
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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.
Gary Levy, M.D. principal investigator
University Health Network, University of Toronto
Leslie Lilly, M.D. study chair
University Health Network, Toronto
Nazia Selzner, M.D. PhD. study chair
University Health Network, Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study of Immunosuppression and Immune Tolerance, run by University of Toronto at 1 site in Canada.
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 5 inclusion and 7 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: finished, as of the sponsor's last update on 30 Sep 2021. 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 Canada. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Validation of Tolerance Gene Expression Profile (time frame: Enrollment to one year post cessation of immunosuppression). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02541916, which also lists 1 linked publication.
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 30 Sep 2021.