Clinical Trial: Parathyroid and Thymus Transplantation in DiGeorge #931

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Parathyroid and Thymus Transplantation in DiGeorge Syndrome, #931

Brief Summary: This study has three primary purposes: to assess parathyroid function after parathyroid transplantation in infants with Complete DiGeorge syndrome; to assess immune function development after transplantation; and, to assess safety and tolerability of the procedures. This is a Phase 1, single site, open, non-randomized clinical protocol. Enrollment is closed and study intervention is complete for all enrolled subjects; but subjects continue for observation and follow-up. Subjects under 2 years old with complete DiGeorge syndrome (atypical or typical) received thymus transplantation. Subjects received pre-transplant immune suppression with rabbit anti-human-thymocyte-globulin. Subjects with hypoparathyroidism and an eligible parental donor received thymus and parental parathyroid transplantation. A primary hypothesis: Thymus/Parathyroid transplant subjects will need less calcium and/or calcitriol supplementation at 1 year post-transplant as compared to historical controls.

Detailed Summary:

Detailed: DiGeorge Syndrome is a complex of three problems, 1) cardiac defects, 2) parathyroid deficiency, and 3) absence of the thymus, resulting in profound T-cell deficiency. There is a spectrum of disease in DiGeorge syndrome with respect to all three defects. There is no safe and effective treatment for DiGeorge Syndrome and most patients die by the age of two. For patients with a severe T cell defect, the PI has shown that thymus transplantation is safe and efficacious under other clinical protocols. Research subjects with complete typical and atypical DiGeorge syndrome were eligible for this study. Subjects with athymia and profound hypoparathyroidism were eligible for parental parathyroid transplantation in this protocol. DiGeorge syndrome infants, who have successful thymus transplants but have hypoparathyroidism, must go to the clinic for frequent calcium levels and to the hospital for calcium infusions; infants with hypoparathyroidism are at risk for seizures from low calcium. Approximately ½ of infants with profound hypoparathyroidism will develop nephrocalcinosis. Depending on T cell phenotype and function, subjects were given one of two different immunosuppression regimens. Typical complete DiGeorge subjects (with proliferative T cell function < 50,000 cpm) received Thymoglobulin pre-transplantation. Typical complete DiGeorge subjects (with proliferative cell response to PHA > 50,000 cpm) and atypical DiGeorge subjects (with proliferative T cell response to PHA < 75,000 cpm) received Thymoglobulin (pre-transplantation) and cyclosporine (pre-transplantation and post-transplantation). Thymoglobulin was used in part to prevent graft rejection and also to deplete any T cells in the donor parathyroid. Cyclosporine was used to deplete activated T cells in the recipient. For all subjects, acetaminophen, diphenhydramine, and methylprednisolone were given concurrently with the rabbit anti-human thymocy
Sponsor: M. Louise Markert

Current Primary Outcome: Efficacy parameter: use of calcium/calcitriol at 1 year post-transplantation. [ Time Frame: 1 year after thymus transplantation ]

Subjects wtih complete DiGeorge anomaly who have received thymus and parathyroid transplants and survived to one year


Original Primary Outcome: Efficacy parameter: use of calcium/calcitriol at 1 year post-transplantation. [ Time Frame: Recipients followed indefinitely; Parathyroid Donors followed 30-days post-transplant ]

Current Secondary Outcome:

  • Efficacy parameters: ionized calcium [ Time Frame: 10-14 months after thymus transplantation ]
    Ionized calcium (normal values are 1.2 - 1.37 mmol/L)
  • Efficacy parameters: CD3 count [ Time Frame: 10-14 months after thymus transplantation ]
    CD3 count/mm3
  • Efficacy parameters: CD4 count [ Time Frame: 10-14 months after thymus transplantation ]
    CD4 count/mm3
  • Efficacy parameters: CD8 count [ Time Frame: 10-14 months after thymus transplantation ]
    CD8 count/mm3
  • Efficacy parameters: naive CD4 count [ Time Frame: 10-14 months after thymus transplantation ]
    naive CD4 count/mm3
  • Efficacy parameters: naive CD8 count [ Time Frame: 10-14 months after thymus transplantation ]
    naive CD8 count/mm3
  • Efficacy parameters: proliferative response to phytohemagglutinin [ Time Frame: approximately 1 year after thymus transplantation (8.9 to 17.8 months after transplantation) ]
    proliferative response to phytohemagglutinin in counts per minute
  • Efficacy parameters: proliferative response to tetanus toxoid [ Time Frame: approximately 1 year after thymus transplantation (8.9 to 17.8 months after transplantation) ]
    proliferative response to tetanus toxoid in counts per minute
  • Efficacy parameters: spectra typing at 1 year post transplantation [ Time Frame: approximately 1 year after thymus transplantation (12.1 to 18.0 months after transplantation) ]
    Variability of CD4 T cell receptor beta repertoire as assessed by the Kullback-Leibler divergence (DKL)


Original Secondary Outcome: Efficacy parameters: ionized calcium; CD3,CD4,&CD8 numbers; naive CD4&CD8 numbers; proliferative Tcell response to mitogens & antigens; & TCR repertoire variability. Endocrine & immunologic results will be tabulated using standard descriptive statistics. [ Time Frame: Indefinitely ]

Information By: Duke University

Dates:
Date Received: November 30, 2007
Date Started: January 2005
Date Completion: June 2027
Last Updated: April 28, 2017
Last Verified: April 2017