We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Thymus Transplantation With Immunosuppression (884)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00579709
First Posted: December 24, 2007
Last Update Posted: July 28, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Institutes of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Enzyvant Therapeutics GmbH
Information provided by (Responsible Party):
M. Louise Markert, Duke University Medical Center
December 20, 2007
December 24, 2007
July 28, 2017
July 2002
December 2006   (Final data collection date for primary outcome measure)
Safety & tolerability of Thymoglobulin and cyclosporine followed by thymus transplantation: Survival at 1 year post-transplantation. [ Time Frame: 1 year post-transplantation ]
Same as current
Complete list of historical versions of study NCT00579709 on ClinicalTrials.gov Archive Site
  • 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
  • Safety: use of post transplant immunosuppression. [ Time Frame: Ongoing ]
  • Allograft biopsy used to evaluate thymopoiesis and graft rejection. Analysis includes presence of cortex and medulla, Hassall bodies, thymocytes with cortical phenotype, and any evidence of graft rejection. [ Time Frame: 2 to 3 months post-transplant ]
  • Development of immune function: CD4 & CD8 count; naive CD4 & CD8 count; PHA response; T cell proliferative response to tetanus toxoid; and immunoscope profile. These will be evaluated in descriptive manner. [ Time Frame: 1 year post-transplantation ]
Not Provided
Not Provided
 
Thymus Transplantation With Immunosuppression
Thymus Transplantation With Immunosuppression, #884
The research purpose is to determine if thymus transplantation with immunosuppression is a safe and effective treatment for complete DiGeorge anomaly. The research includes studies to evaluate whether thymus transplantation results in complete DiGeorge anomaly subjects developing a normal immune system.

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.

Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • DiGeorge Syndrome
  • DiGeorge Anomaly
  • Complete DiGeorge Anomaly
  • Complete DiGeorge Syndrome
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.

Other Names:
  • IND 9836
  • Thymus Tissue Transplant
Experimental: 1
Thymus Tissue for Transplantation
Intervention: Biological: Thymus Tissue for Transplantation

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
15
June 2027
December 2006   (Final data collection date for primary outcome measure)

Transplant Inclusion

  • No age limit
  • Thyroid studies must be done and if abnormal, must be on therapy

DiGeorge diagnosis - must have 1 symptom from the following list:

  • Heart defect
  • Hypocalcemia requiring replacement
  • 22q11 hemizygosity
  • 10p13 hemizygosity
  • CHARGE association
  • Abnormal ears plus mother with diabetes (type I, type II, or gestational)

Atypical Diagnosis:

  • Must have, or have had, a rash. If rash present, biopsy of rash must show T cells in skin. If rash & adenopathy resolved, must still have oligoclonal T cells.
  • Within 1 month of tx must have PHA response >20 fold above background or >5,000 cpm, whichever is higher, or response can be < this.
  • Circulating CD3+ T cells >50/mm3 but CD45RA+CD62L+CD3+ T cells <50/mm or <5% of CD3 count, whichever is higher (must be done 2x)
  • Immunoscope with >40% oligoclonal TCRBV families. A 2nd test per sponsor discretion if T cell numbers increase or activation status changes.
  • If TREC done pre-tx must have TRECs <100 per 100,000 CD3+ cells.

Typical Diagnosis:

  • Circulating CD3+ CD45RA+ CD62L+ T cells and <50/mm3 or <5% of total T cells
  • PHA response >20 fold above background or >5,000 cpm, whichever is higher.
  • 2 studies must show similar immunological findings qualify for this study.
  • TRECs, if done, should be <100/100,000 CD3 cells

Transplant Exclusion:

  • Heart surgery <4 weeks pre-tx date
  • Heart surgery anticipated w/in 3 months of proposed tx
  • Rejection by surgeon or anesthesiologist as surgical candidates
  • Lack of sufficient muscle tissue to accept 0.2 grams/kg transplant
Sexes Eligible for Study: All
Child, Adult, Senior
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00579709
Pro00013734
R01AI047040 ( U.S. NIH Grant/Contract )
R01AI054843 ( U.S. NIH Grant/Contract )
3R56AI047040-11A1S1 ( U.S. NIH Grant/Contract )
R56 Bridge R01AI4704011A1 ( Other Identifier: NIH American Recovery and Reinvestment Act (ARRA) of 2009 )
2R01AI047040-11A2 ( U.S. NIH Grant/Contract )
5K12HD043494-09 ( U.S. NIH Grant/Contract )
#884
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
M. Louise Markert, Duke University Medical Center
M. Louise Markert
  • National Institutes of Health (NIH)
  • National Institute of Allergy and Infectious Diseases (NIAID)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • Enzyvant Therapeutics GmbH
Principal Investigator: M. Louise Markert, MD, PhD Duke University Medical Center, Pediatrics, Allergy & Immunology
Duke University
July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP