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This is a prospective multi-center, longitudinal study to determine efficacy of 50 percent Immunosuppression (IS) reduction. One hundred fully eligible participants will reduce IS by 50 percent in two steps. Liver tests will be checked every 0.5 months through month 4, once a month through month 12, and every other month through month 18. Liver transplant (LTx) center visits will take place at screening, months 6, 12 and 18 after initiating IS dose reduction. A protocol driven liver biopsy to adjudicate the endpoint will be performed at 18 months. The duration of the study from time of starting IS dose reduction to the primary endpoint assessment is 18 months.
The primary objective is to assess the efficacy of 50 percent IS dose reduction in children with Liver transplants (LTxs)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IS dose reduction | Experimental | Eligible participants will reduce immunosuppression (IS) by 50 percent in two steps. For subjects taking tacrolimus once daily:
For subjects taking tacrolimus twice daily:
For participants taking different doses of tacrolimus in the morning and evening, the clinical site will confer will the protocol chair and PI to determine the schedule for IS reduction |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tacrolimus reduction | Procedure | Prospective multi-center, longitudinal study to determine the success rate of 50% immunosuppression (IS) dose reduction. One hundred fully eligible participants will reduce IS by 50% in two steps |
| Measure | Description | Time Frame |
|---|---|---|
| Achieving successful 50 percent Immunosuppression (IS) reduction | Defined as meeting both biochemical and histological criteria of stability | At 18 months |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical severity of Acute rejection (AR) episodes | Clinical severity - treatment required for resolution | At 18 months |
| Histological severity of Acute rejection (AR) episodes | At 18 months |
| Measure | Description | Time Frame |
|---|---|---|
| EXPLORATORY: The association between donor specific antibody (DSA) status and the outcome of 50 percent Immunosuppression (IS) dose reduction | At 18 months | |
| EXPLORATORY: The association between the degree of molecular mismatch and the outcome of 50 percent Immunosuppression (IS) dose reduction |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ada Chao | Contact | 415-353-7004 | ada.chao@ucsf.edu |
| Name | Affiliation | Role |
|---|---|---|
| Sandy Feng, MD, Ph.D. | University of California San Francisco School of Medicine: Transplantation | Study Chair |
| John Bucuvalas, M.D. | Icahn School of Medicine at Mount Sinai: Transplantation | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Benioff Children's Hospital | Not yet recruiting | San Francisco | California | 94143 | United States |
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| Label | URL |
|---|---|
| Division of Allergy, Immunology, and Transplantation | View source |
| National Institute of Allergy and Infectious Diseases | View source |
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| The proportion of participants who experience Acute rejection (AR) | Defined as either biopsy-proven or clinical AR | At 18 months |
| Achieving clinically successful 50 percent Immunosuppression (IS) reduction | Defined as meeting biochemical but not histological criteria of stability | At 18 months |
| At 18 months |
| EXPLORATORY: The association between the degree of molecular mismatch and the development of de novo donor specific antibody (DSA) | At 18 months |
| EXPLORATORY: The proportion of participants who develop de novo donor specific antibody (DSA) | At 18 months |
| EXPLORATORY: The association of intrapatient variability of tacrolimus blood levels and the outcome of 50 percent Immunosuppression (IS) dose reduction | At 18 months |
| EXPLORATORY: The association between tacrolimus exposure and the outcome of 50 percent Immunosuppression (IS) dose reduction | At 18 months |
| MECHANISTIC: The spatial metabolic landscape of liver biopsies and its relationship with clinical phenotypes | At 18 months |
| MECHANISTIC: The spatial metabolic landscape of liver biopsies and its relationship with cell phenotypes | At 18 months |
| MECHANISTIC: The spatial metabolic landscape of liver biopsies and its relationship with iSYNs | At 18 months |
| MECHANISTIC: Integration of image mass cytometry and state-of-the-art single-cell spatial transcriptomics to exhaustively map the immune microenvironment of liver allografts | At 18 months |
| MECHANISTIC: Pathway analysis of whole transcriptome data for iSYNs | At 18 months |
| MECHANISTIC: Nature of specific cell populations participating in iSYNs | At 18 months |
| MECHANISTIC: Density of aiSYNs in the baseline and in longitudinal biopsies | At 18 months |
| Children's Hospital Colorado | Not yet recruiting | Aurora | Colorado | 80045 | United States |
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| MedStar Georgetown University Hospital | Not yet recruiting | Washington D.C. | District of Columbia | 20007 | United States |
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| Emory University School of Medicine/Children's Healthcare of Atlanta | Not yet recruiting | Atlanta | Georgia | 30307 | United States |
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| Ann and Robert H. Lurie Children's Hospital of Chicago | Recruiting | Chicago | Illinois | 60611 | United States |
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| Icahn School of Medicine at Mount Sinai | Not yet recruiting | New York | New York | 10029 | United States |
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| Columbia University Medical Center | Not yet recruiting | New York | New York | 10032 | United States |
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| Cincinnati Children's Hospital Medical Center | Recruiting | Cincinnati | Ohio | 45229 | United States |
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| Children's Hospital of Philadelphia | Not yet recruiting | Philadelphia | Pennsylvania | 15224 | United States |
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| Monroe Carell Jr. Children's Hospital at Vanderbilt | Not yet recruiting | Nashville | Tennessee | 37232 | United States |
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