Thymus Transplantation With Immunosuppression (884)
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|ClinicalTrials.gov Identifier: NCT00579709|
Recruitment Status : Active, not recruiting
First Posted : December 24, 2007
Last Update Posted : July 28, 2017
|Condition or disease||Intervention/treatment||Phase|
|DiGeorge Syndrome DiGeorge Anomaly Complete DiGeorge Anomaly Complete DiGeorge Syndrome||Biological: Thymus Tissue for Transplantation||Phase 1|
DiGeorge anomaly is a complex of cardiac defects, parathyroid deficiency, and thymus absence, resulting in profound T-cell deficiency. There is a spectrum of disease in DiGeorge anomaly with respect to all three defects. For complete DiGeorge anomaly subjects with severe T cell defect, the PI had shown that thymus transplantation is safe and efficacious without pretransplantation immunosuppression and with pretransplantation Thymoglobulin and cyclosporine.
Some DiGeorge patients have very poor T cell function and are at risk of death from infection or other immune problems; however, these patients have enough T cell function to reject grafts. This protocol was designed for these patients. Atypical phenotype and some typical phenotype DiGeorge subjects were included in this protocol.
Atypical complete DiGeorge anomaly patients have rash, lymphadenopathy, and oligoclonal T cell proliferations. The T cells have no markers of thymic function (they do not co-express CD45RA and CD62L; they do not contain T cell receptor rearrangement excision circles, TRECs).
Typical complete DiGeorge anomaly patients in this protocol are those whose PHA response >20 fold. Although these patients have very low T cell function, it may be enough to reject a transplant, so Thymoglobulin was used.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Thymus Transplantation With Immunosuppression, #884|
|Study Start Date :||July 2002|
|Primary Completion Date :||December 2006|
|Estimated Study Completion Date :||June 2027|
Thymus Tissue for Transplantation
Biological: Thymus Tissue for Transplantation
3 Thymoglobulin doses given prior to thymus tx. Atypical subjects given Cyclosporine (Csa) pre-tx. Desired Csa concentration 180-300ng/ml. If post-tx T cell count remained <4000/cumm Csa weaned over 8 weeks. If T cell >4,000/cumm, Csa held at 180-300ng/ml.
Thymus tissue, donor, & mother of donor were screened for transplant safety. In operating room, thymic slices were transplanted into quadriceps muscle in 1 or both legs.
Subjects had routine blood research immune evaluations. 2-3 months post-tx, open biopsy of allograft. Immune blood studies continued on surviving subjects until January 2010. Biological Mother: Mother provided blood sample used for DNA extraction, to identify/look for maternal T cell presence in recipient pre-tx, and/or for immune testing post-tx.
- Safety & tolerability of Thymoglobulin and cyclosporine followed by thymus transplantation: Survival at 1 year post-transplantation. [ Time Frame: 1 year post-transplantation ]
- Use of additional post transplant immunosuppression after that listed in the protocol. [ Time Frame: The post thymus transplantation period ]Use of additional post transplant immunosuppression after that listed in the protocol.
- Allograft biopsy used to evaluate graft rejection [ Time Frame: 2 to 4 months post-transplant ]Evidence of thymus allograft rejection by immunohistochemistry of biopsy
- CD3 count [ Time Frame: 10 - 14 months post-transplantation ]CD3 count in cells/mm3
- Thymopoiesis [ Time Frame: 2-4 months after thymus transplantation ]Evidence of thymopoiesis in thymus allograft by immunohistochemistry of a biopsy
- CD4 count [ Time Frame: 10-14 months after thymus transplantation ]CD4 count in cells/mm3
- CD8 count [ Time Frame: 10-14 months after thymus transplantation ]CD8 count in cells/mm3
- naive CD4 count [ Time Frame: 10-14 months after thymus transplantation ]naive CD4 count in cells/mm3
- naive CD8 count [ Time Frame: 10-14 months after thymus transplantation ]naive CD8 count in cells/mm3
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00579709
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||M. Louise Markert, MD, PhD||Duke University Medical Center, Pediatrics, Allergy & Immunology|