Thymus Transplantation in DiGeorge Syndrome #668

This study is ongoing, but not recruiting participants.
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)
Information provided by (Responsible Party):
M. Louise Markert, Duke University Medical Center Identifier:
First received: December 17, 2007
Last updated: September 3, 2015
Last verified: September 2015
The study purpose is to determine whether thymus transplantation without immunosuppression is effective in treating typical complete DiGeorge syndrome.

Condition Intervention Phase
DiGeorge Syndrome
Complete Typical DiGeorge Anomaly
Biological: Thymus Tissue for Transplantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Thymus Transplantation in Complete DiGeorge Syndrome #668

Resource links provided by NLM:

Further study details as provided by Duke University:

Primary Outcome Measures:
  • Survival rate at one year post-transplantation. [ Time Frame: One year post-transplantation. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • T cell proliferative response to tetanus toxoid [ Time Frame: Approximately 1 year after transplantation ] [ Designated as safety issue: No ]
    Proliferative response that is 10 fold over background

Enrollment: 26
Study Start Date: November 2001
Estimated Study Completion Date: June 2027
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Thymus Tissue for Transplantation in Complete DiGeorge Syndrome
Biological: Thymus Tissue for Transplantation
Thymus transplantation is done using allogeneic cultured postnatal tissue from unrelated donors. Thymus tissue, the donor, & donor's mother were screened for safety. Approximately 2-3 weeks post-harvest thymus slices were transplanted into the recipient's quadriceps. Dose is number of grams of transplanted tissue divided by the recipient's weight in kilograms. Minimum dose was 4 g/m2. Maximum dose 18g/m2. At time of transplantation, a skin biopsy was obtained to look for preexisting T cells. 2-3 months post-transplant allograft biopsy to evaluate for thymopoiesis & graft rejection. At time of biopsy, skin biopsy done to look for T cell clonal populations. Post-transplant, subjects followed by routine research immune evaluations, using blood samples for 2 years.
Other Names:
  • Thymus Tissue
  • Thymus Tissue Transplantation
  • Thymus Transplant

Detailed Description:

There is no safe and effective treatment for DiGeorge syndrome and most patients die by the age of two. Complete DiGeorge syndrome is characterized by very low T cell or very low naïve T cell numbers. In this study, typical complete DiGeorge syndrome subjects received human postnatal cultured thymus tissue transplants. Thymus tissue that would otherwise be discarded was transplanted into DiGeorge subjects in the operating room. At the time of transplantation, a skin biopsy was obtained to look for any preexisting T cells. After transplantation, subjects were followed by routine research immune evaluations, using blood samples obtained every 2-4 weeks. At approximately 2-3 months post-transplantation subjects underwent an open biopsy of the allograft. The biopsy was done under general anesthesia in the operating room. At the time of the graft biopsy, another skin biopsy was obtained to look for clonal populations of T cells.

The protocol aims include: assessing thymopoiesis in the allograft biopsy; assessing immunoreconstitution of complete DiGeorge syndrome subjects after postnatal allogeneic thymus transplantation; assessing minimally invasive methods of assessing thymopoiesis (flow cytometry and polymerase chain reaction (PCR); assessing pre-transplant T cells which do not proliferate in response to mitogens (focusing on NK-T cells); and, assessing thymus transplantation safety and toxicity.


Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of complete DiGeorge syndrome which is either: T cells with < 50/mm3 with naive phenotype; or < 5% CD3 + T cells with naive T cell phenotype.
  • Diagnosis of typical DiGeorge syndrome phenotype: < 50 T cells/cumm and very low proliferative responses to mitogens (e.g. < 20 fold response to mitogen phytohemagglutinin).
  • Proliferative response to PHA < 20 fold above background or < 5000 counts per minute(cpm), whichever is higher.

{Note: Subjects with PHA responses 20 fold or more over background or > 5,000 cpm, whichever is higher, may be enrolled in another thymus transplant protocol.}

  • Must have heart disease; hypocalcemia requiring replacement; 22q11 or 10p13 hemizygosity; CHARGE association; or must be child of diabetic mother and have abnormal ears.

Exclusion Criteria:

  • Those who do not meet inclusion criteria
  • Atypical DiGeorge syndrome phenotype
  • Rash indicating atypical DiGeorge syndrome phenotype.

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT00576407

United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
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)
Principal Investigator: M. Louise Markert, MD, PhD Duke University Medical Center, Pediatrics, Allergy & Immunology
  More Information

Markert ML and Devlin BH. Thymic reconstitution (in Rich RR, Shearer WT, Fleischer T, Schroeder HW, Weyand CM, Frew A, eds., Clinical Immunology 3rd edn., Elsevier, Edinburgh) p 1253-1262, 2008.
Markert ML, Devlin BH, McCarthy EA, Chinn IK, Hale LP. Thymus Transplantation in Thymus Gland Pathology: Clinical, Diagnostic, and Therapeutic Features. Eds Lavinin C, Moran CA, Morandi U, Schoenhuber R. Springer-Verlag Italia, Milan, 2008, pp 255-267.

Responsible Party: M. Louise Markert, Associate Professor, Duke University Medical Center, Pediatric Allergy & Immunology, Duke University Medical Center Identifier: NCT00576407     History of Changes
Other Study ID Numbers: Pro00009955  2R01AI047040-11A2  R56 Bridge R01AI4704011A1  5K12HD043494-09  R01AI047040  3R56AI047040-11A1S1  R01AI054843  #668 
Study First Received: December 17, 2007
Last Updated: September 3, 2015
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Duke University:
Thymus Transplantation
DiGeorge Syndrome
Low T cell numbers
Primary immunodeficiency
DiGeorge Anomaly
Complete DiGeorge
Typical DiGeorge

Additional relevant MeSH terms:
Craniofacial Abnormalities
DiGeorge Syndrome
22q11 Deletion Syndrome
Abnormalities, Multiple
Cardiovascular Abnormalities
Cardiovascular Diseases
Chromosome Disorders
Congenital Abnormalities
Endocrine System Diseases
Genetic Diseases, Inborn
Heart Defects, Congenital
Heart Diseases
Lymphatic Abnormalities
Lymphatic Diseases
Musculoskeletal Abnormalities
Musculoskeletal Diseases
Parathyroid Diseases
Pathologic Processes processed this record on May 26, 2016