DiGeorge SyndromePhase 1NCT00566488
Parathyroid and Thymus Transplantation in DiGeorge #931
A Phase 1 study testing Thymus/Parathyroid Transplantation in people with DiGeorge Syndrome and Hypoparathyroidism, run by Sumitomo Pharma Switzerland GmbH at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 24 months
- Conditions the study is for
- DiGeorge Syndrome, Hypoparathyroidism, Complete DiGeorge Syndrome
- What is being tested?
- Thymus/Parathyroid Transplantation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2005to Dec 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 24 months
- All sexes
- No healthy volunteers
- Child
Transplant Inclusion:
- Complete DiGeorge syndrome (typical or atypical) - may have DiGeorge as part of 22q11 hemizygosity, CHARGE association, or diabetic embryopathy or they may have no associated syndromes.
- Must have 1 of following:
- Circulating CD3+ T cells < 50/mm3; or
- Circulating CD3+ T cells that also positive for CD45RA and CD62L must be <50/mm3 or must be < 5% of total T cells.
- Must be <24 months old
- Laboratory studies must be done w/in 1 month of treatment:
- Thyroid studies - if abnormal must be on therapy, if recommended by endocrinology:
- PT and PTT must be <2x upper limits of normal (ULN)
- Absolute neutrophil count must be >500/mm3
- Platelet count must be >50,000/mm3
- AST and ALT must be <5x ULN
- Creatinine must be <1.5 mg/dl
- Parents must agree to have infant stay in Durham until thymus biopsy is done 2-3 months post-treatment.
- Typical subjects must not have a rash with T cells on biopsy nor lymphadenopathy.
- Atypical subjects have rash with T cells on biopsy; may have lymphadenopathy.
- PHA proliferative responses must be tested 2x • Atypical: PHA response must be <75,000cpm on 2 tests; test can be done while on immunosuppression.
Additional Criteria for Parathyroid Treatment Inclusion
- Hypoparathyroidism
- At least 1 parent must agree to be parathyroid donor
- Must require calcium supplementation to maintain ionized calcium >1.0 mmol/L. Alternatively, intact PTH must be <lower limit of normal when ionized calcium is <1.2 mmol/L. (Intact PTH measured 2x pre-treatment.)
DiGeorge Treatment Exclusion:
- Heart surgery conducted <4 weeks pre-treatment
- Heart surgery anticipated w/in 3 months of treatment
- Rejection by surgeon or anesthesiologist as surgical candidate
- Lack of sufficient muscle tissue to accept 0.2gms/kg treatment
- Prior attempts at immune reconstitution, such as bone marrow treatment or previous thymus treatment
- Doesn't commit to remaining at Duke until thymus allograft biopsy
Parathyroid Donor Inclusion:
- Serum calcium in normal range
- Normal parathyroid hormone function
- HLA typing must be consistent with parentage.
- Must not be on anticoagulation or can come off
- Parent chosen for donation will be the 1 sharing most HLA alleles with thymus donor
- HLA-DR matching preferred over HLA class I matching. If there no HLA matching at all, then either parent will be acceptable if meets other criteria.
- Negative for EBV; CMV; HIV-1; Syphilis; West Nile virus; Hepatitis B; Hepatitis C; pregnancy; \& evidence of head/neck infection
- Fiberoptic nasolaryngoscopy shows vocal cords functioning normally.
- Normal thyroid function
- No history of cancer
- The infant-recipient has 2 living involved parents.
Parathyroid Donor Exclusion:
- Infant recipient doesn't have 2 living involved parents
- Animal tissue/organ recipient
- EBV
- CMV
- HIV-1
- Syphilis
- West Nile virus
- Hepatitis B
- Hepatitis C
- Pregnant
- Evidence of head/neck infection
- Vocal cords not functioning normally.
- Thyroid abnormalities
- Hyperparathyroidism
- History of cancer
- Mad cow disease (positive)
- SARS(and exposure)
- Smallpox exposure
Biological Mother of DiGeorge Subjects Inclusions:
Mother must be competent to consent or assent to study participation and willing to provide blood sample. No other inclusion/exclusion.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27705
About this study
Official title: Parathyroid and Thymus Transplantation in DiGeorge Syndrome, #931
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.
Read the detailed description
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. 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 thymocyte globulin. The thymus was cultured in standard medium for 10-21 days to deplete mature thymocytes which could cause GVHD. In the operating room, thymus tissue was placed in the quadriceps muscle in one or both legs. The parathyroid donation was preferably done at the same time as the thymus transplantation. Parathyroid tissue was placed in the quadriceps muscle in only one leg, using the same incision as the thymus transplantation. Depending on post-transplant immune status, subjects may have received cyclosporine and steroids.
For 3 months after thymus transplantation, T cells were monitored by flow cytometry approximately every 2-4 weeks. Alternatively, absolute lymphocyte count was used as the maximum possible T cell number. At 2-3 months post-transplant, the subject may have had a thymus allograft biopsy, done under general anesthesia in the operating room. The biopsy was approximately 4 pea-sized (3x3mm) portions of muscle tissue where the thymus transplant had been inserted. Using immunohistochemistry, the biopsy determined thymopoiesis and any graft rejection. The parathyroid was not biopsied because it is very small; doing a biopsy could remove all of the parathyroid tissue. A research skin biopsy (at site of skin incision at the time of transplantation) was done to determine whether T cells were present pre-transplantation. A skin biopsy was also done at the time of thymus graft biopsy to look for clonal T cell populations. For all subjects who developed T cells, post-transplantation pneumocystis prophylaxis was used for approximately 1 year and IV immunoglobulin for approximately 2 years.
- Being tested
- Thymus/Parathyroid Transplantation
- Keywords
- Thymus Transplantation, Parathyroid Transplantation, DiGeorge Syndrome, Hypoparathyroidism, Athymia
- Medical subject headings
- DiGeorge Syndrome, Hypoparathyroidism, Thymic aplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Thymus/Parathyroid TransplantationBiological
Also called IND 9836, Thymus Tissue
Thymus tissue, thymus donor, mother of thymus donor, \& parental parathyroid donor screened for transplant safety. Depending on T cell phenotype \& function, subjects were given 1 of 2 immunosuppression regimes. All received rabbit anti thymocyte globulin pretransplantation. Others also received cyclosporine pre \& post-transplantation. The thymus dose was over 0.2 grams/kg recipient weight. Thymus transplant occurred in operating room; thymic slices were placed in quadriceps. Parathyroid harvest was done under general anesthesia. One parathyroid gland was minced and placed in quadriceps muscle. There was no dose in mg. An open biopsy of thymus allograft was done 2-3 months post-transplant. Biopsy tissue was examined by immunohistochemistry to evaluate for thymopoiesis \& graft rejection.
| Study group | Role | What they receive |
|---|---|---|
| Thymus and Parathyroid transplantation | Experimental | Thymus/Parathyroid Transplantation in Complete DiGeorge Syndrome Infants Receives: Biological: Thymus/Parathyroid Transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy parameter: use of calcium/calcitriol at 1 year post-transplantation.
Subjects wtih complete DiGeorge anomaly who have received thymus and parathyroid transplants and survived to one year
Measured: 1 year after thymus transplantation
Secondary outcomes (9)
Efficacy parameters: ionized calcium
Ionized calcium (normal values are 1.2 - 1.37 mmol/L)
Measured: 10-14 months after thymus transplantation
Efficacy parameters: CD3 count
CD3 count/mm3
Measured: 10-14 months after thymus transplantation
Efficacy parameters: CD4 count
CD4 count/mm3
Measured: 10-14 months after thymus transplantation
Efficacy parameters: CD8 count
CD8 count/mm3
Measured: 10-14 months after thymus transplantation
Efficacy parameters: naive CD4 count
naive CD4 count/mm3
Measured: 10-14 months after thymus transplantation
Efficacy parameters: naive CD8 count
naive CD8 count/mm3
Measured: 10-14 months after thymus transplantation
Efficacy parameters: proliferative response to phytohemagglutinin
proliferative response to phytohemagglutinin in counts per minute
Measured: approximately 1 year after thymus transplantation (8.9 to 17.8 months after transplantation)
Efficacy parameters: proliferative response to tetanus toxoid
proliferative response to tetanus toxoid in counts per minute
Measured: approximately 1 year after thymus transplantation (8.9 to 17.8 months after transplantation)
Efficacy parameters: spectra typing at 1 year post transplantation
Variability of CD4 T cell receptor beta repertoire as assessed by the Kullback-Leibler divergence (DKL)
Measured: approximately 1 year after thymus transplantation (12.1 to 18.0 months after transplantation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2007 (estimated)
- Study startJan 2005
- Primary completionAug 2007
- Study completionDec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for DiGeorge SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sumitomo Pharma Switzerland GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Food and Drug Administration (FDA), 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)
- Responsible party
- Sponsor
- Investigators
- M. Louise Markert, MD, PhD, Principal investigator, Duke University Medical Center, Pediatrics, Allergy & Immunology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00566488
- Sponsor's protocol ID
- Pro00016482
- Other IDs
- R01AI047040, 5K12HD043494-09, R01AI054843, FDA-FD-R-002606, 2R01AI047040-11A2, R56 Bridge R01AI4704011A1, 3R56AI047040-11A1S1, #931
- Status last verified
- Apr 2020
- First submitted
- 30 Nov 2007
- Last updated
- 4 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Markert ML, Marques JG, Neven B, Devlin BH, McCarthy EA, Chinn IK, Albuquerque AS, Silva SL, Pignata C, de Saint Basile G, Victorino RM, Picard C, Debre M, Mahlaoui N, Fischer A, Sousa AE. First use of thymus transplantation therapy for FOXN1 deficiency (nude/SCID): a report of 2 cases. Blood. 2011 Jan 13;117(2):688-96. doi: 10.1182/blood-2010-06-292490. Epub 2010 Oct 26.
PubMed 20978268Chinn IK, Devlin BH, Li YJ, Markert ML. Long-term tolerance to allogeneic thymus transplants in complete DiGeorge anomaly. Clin Immunol. 2008 Mar;126(3):277-81. doi: 10.1016/j.clim.2007.11.009. Epub 2007 Dec 26.
PubMed 18155964Selim MA, Markert ML, Burchette JL, Herman CM, Turner JW. The cutaneous manifestations of atypical complete DiGeorge syndrome: a histopathologic and immunohistochemical study. J Cutan Pathol. 2008 Apr;35(4):380-5. doi: 10.1111/j.1600-0560.2007.00816.x.
PubMed 18333898Markert ML, Sarzotti M, Ozaki DA, Sempowski GD, Rhein ME, Hale LP, Le Deist F, Alexieff MJ, Li J, Hauser ER, Haynes BF, Rice HE, Skinner MA, Mahaffey SM, Jaggers J, Stein LD, Mill MR. Thymus transplantation in complete DiGeorge syndrome: immunologic and safety evaluations in 12 patients. Blood. 2003 Aug 1;102(3):1121-30. doi: 10.1182/blood-2002-08-2545. Epub 2003 Apr 17.
PubMed 12702512Chinn IK, Olson JA, Skinner MA, McCarthy EA, Gupton SE, Chen DF, Bonilla FA, Roberts RL, Kanariou MG, Devlin BH, Markert ML. Mechanisms of tolerance to parental parathyroid tissue when combined with human allogeneic thymus transplantation. J Allergy Clin Immunol. 2010 Oct;126(4):814-820.e8. doi: 10.1016/j.jaci.2010.07.016. Epub 2010 Sep 15.
PubMed 20832849Chinn IK, Milner JD, Scheinberg P, Douek DC, Markert ML. Thymus transplantation restores the repertoires of forkhead box protein 3 (FoxP3)+ and FoxP3- T cells in complete DiGeorge anomaly. Clin Exp Immunol. 2013 Jul;173(1):140-9. doi: 10.1111/cei.12088.
PubMed 23607606Markert ML, Devlin BH, Chinn IK, McCarthy EA. Thymus transplantation in complete DiGeorge anomaly. Immunol Res. 2009;44(1-3):61-70. doi: 10.1007/s12026-008-8082-5.
PubMed 19066739Markert 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.
Markert ML, Devlin BH, Chinn IK, McCarthy EA, Li YJ. Factors affecting success of thymus transplantation for complete DiGeorge anomaly. Am J Transplant. 2008 Aug;8(8):1729-36. doi: 10.1111/j.1600-6143.2008.02301.x. Epub 2008 Jun 28.
PubMed 18557726Hudson LL, Louise Markert M, Devlin BH, Haynes BF, Sempowski GD. Human T cell reconstitution in DiGeorge syndrome and HIV-1 infection. Semin Immunol. 2007 Oct;19(5):297-309. doi: 10.1016/j.smim.2007.10.002. Epub 2007 Nov 26.
PubMed 18035553Markert ML, Li J, Devlin BH, Hoehner JC, Rice HE, Skinner MA, Li YJ, Hale LP. Use of allograft biopsies to assess thymopoiesis after thymus transplantation. J Immunol. 2008 May 1;180(9):6354-64. doi: 10.4049/jimmunol.180.9.6354.
PubMed 18424759Markert ML, Devlin BH, Alexieff MJ, Li J, McCarthy EA, Gupton SE, Chinn IK, Hale LP, Kepler TB, He M, Sarzotti M, Skinner MA, Rice HE, Hoehner JC. Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants. Blood. 2007 May 15;109(10):4539-47. doi: 10.1182/blood-2006-10-048652. Epub 2007 Feb 6.
PubMed 17284531Markert 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. Thymus transplantation. Clin Immunol. 2010 May;135(2):236-46. doi: 10.1016/j.clim.2010.02.007. Epub 2010 Mar 16.
PubMed 20236866Markert ML, Alexieff MJ, Li J, Sarzotti M, Ozaki DA, Devlin BH, Sedlak DA, Sempowski GD, Hale LP, Rice HE, Mahaffey SM, Skinner MA. Postnatal thymus transplantation with immunosuppression as treatment for DiGeorge syndrome. Blood. 2004 Oct 15;104(8):2574-81. doi: 10.1182/blood-2003-08-2984. Epub 2004 Apr 20.
PubMed 15100156
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Parathyroid and Thymus Transplantation in DiGeorge Syndrome, #931
- ClinicalTrials.gov ID
- NCT00566488
- Acronym / sponsor ID
- Pro00016482
- Keywords
- Thymus Transplantation, Parathyroid Transplantation, DiGeorge Syndrome, Hypoparathyroidism, Athymia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Sumitomo Pharma Switzerland GmbHIndustry (pharma, biotech, devices)
- Collaborators
- Food and Drug Administration (FDA), 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)
- Study start
- Jan 2005
- Primary completion
- Aug 2007 (actual)
- Study completion
- Dec 2019 (actual)
- First posted
- 3 Dec 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 description
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. 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 thymocyte globulin. The thymus was cultured in standard medium for 10-21 days to deplete mature thymocytes which could cause GVHD. In the operating room, thymus tissue was placed in the quadriceps muscle in one or both legs. The parathyroid donation was preferably done at the same time as the thymus transplantation. Parathyroid tissue was placed in the quadriceps muscle in only one leg, using the same incision as the thymus transplantation. Depending on post-transplant immune status, subjects may have received cyclosporine and steroids.
For 3 months after thymus transplantation, T cells were monitored by flow cytometry approximately every 2-4 weeks. Alternatively, absolute lymphocyte count was used as the maximum possible T cell number. At 2-3 months post-transplant, the subject may have had a thymus allograft biopsy, done under general anesthesia in the operating room. The biopsy was approximately 4 pea-sized (3x3mm) portions of muscle tissue where the thymus transplant had been inserted. Using immunohistochemistry, the biopsy determined thymopoiesis and any graft rejection. The parathyroid was not biopsied because it is very small; doing a biopsy could remove all of the parathyroid tissue. A research skin biopsy (at site of skin incision at the time of transplantation) was done to determine whether T cells were present pre-transplantation. A skin biopsy was also done at the time of thymus graft biopsy to look for clonal T cell populations. For all subjects who developed T cells, post-transplantation pneumocystis prophylaxis was used for approximately 1 year and IV immunoglobulin for approximately 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Thymus and Parathyroid transplantation | Experimental | Biological: Thymus/Parathyroid TransplantationThymus/Parathyroid Transplantation in Complete DiGeorge Syndrome Infants |
Who may qualify
- Ages
- Up to 24 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Thymus/Parathyroid TransplantationAlso: IND 9836, Thymus TissueThymus tissue, thymus donor, mother of thymus donor, \& parental parathyroid donor screened for transplant safety. Depending on T cell phenotype \& function, subjects were given 1 of 2 immunosuppression regimes. All received rabbit anti thymocyte globulin pretransplantation. Others also received cyclosporine pre \& post-transplantation. The thymus dose was over 0.2 grams/kg recipient weight. Thymus transplant occurred in operating room; thymic slices were placed in quadriceps. Parathyroid harvest was done under general anesthesia. One parathyroid gland was minced and placed in quadriceps muscle. There was no dose in mg. An open biopsy of thymus allograft was done 2-3 months post-transplant. Biopsy tissue was examined by immunohistochemistry to evaluate for thymopoiesis \& graft rejection. | Biological | Thymus and Parathyroid transplantation |
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
9 secondary outcomes
Efficacy parameters: ionized calcium
Time frame: 10-14 months after thymus transplantation
Efficacy parameters: CD3 count
Time frame: 10-14 months after thymus transplantation
Efficacy parameters: CD4 count
Time frame: 10-14 months after thymus transplantation
Efficacy parameters: CD8 count
Time frame: 10-14 months after thymus transplantation
Efficacy parameters: naive CD4 count
Time frame: 10-14 months after thymus transplantation
Efficacy parameters: naive CD8 count
Time frame: 10-14 months after thymus transplantation
Efficacy parameters: proliferative response to phytohemagglutinin
Time frame: approximately 1 year after thymus transplantation (8.9 to 17.8 months after transplantation)
Efficacy parameters: proliferative response to tetanus toxoid
Time frame: approximately 1 year after thymus transplantation (8.9 to 17.8 months after transplantation)
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2022.
- Background: PubMed 20978268Markert ML, Marques JG, Neven B, Devlin BH, McCarthy EA, Chinn IK, Albuquerque AS, Silva SL, Pignata C, de Saint Basile G, Victorino RM, Picard C, Debre M, Mahlaoui N, Fischer A, Sousa AE. First use of thymus transplantation therapy for FOXN1 deficiency (nude/SCID): a report of 2 cases. Blood. 2011 Jan 13;117(2):688-96. doi: 10.1182/blood-2010-06-292490. Epub 2010 Oct 26.
- Background: PubMed 18155964Chinn IK, Devlin BH, Li YJ, Markert ML. Long-term tolerance to allogeneic thymus transplants in complete DiGeorge anomaly. Clin Immunol. 2008 Mar;126(3):277-81. doi: 10.1016/j.clim.2007.11.009. Epub 2007 Dec 26.
- Background: PubMed 18333898Selim MA, Markert ML, Burchette JL, Herman CM, Turner JW. The cutaneous manifestations of atypical complete DiGeorge syndrome: a histopathologic and immunohistochemical study. J Cutan Pathol. 2008 Apr;35(4):380-5. doi: 10.1111/j.1600-0560.2007.00816.x.
- Background: PubMed 12702512Markert ML, Sarzotti M, Ozaki DA, Sempowski GD, Rhein ME, Hale LP, Le Deist F, Alexieff MJ, Li J, Hauser ER, Haynes BF, Rice HE, Skinner MA, Mahaffey SM, Jaggers J, Stein LD, Mill MR. Thymus transplantation in complete DiGeorge syndrome: immunologic and safety evaluations in 12 patients. Blood. 2003 Aug 1;102(3):1121-30. doi: 10.1182/blood-2002-08-2545. Epub 2003 Apr 17.
- Background: PubMed 20832849Chinn IK, Olson JA, Skinner MA, McCarthy EA, Gupton SE, Chen DF, Bonilla FA, Roberts RL, Kanariou MG, Devlin BH, Markert ML. Mechanisms of tolerance to parental parathyroid tissue when combined with human allogeneic thymus transplantation. J Allergy Clin Immunol. 2010 Oct;126(4):814-820.e8. doi: 10.1016/j.jaci.2010.07.016. Epub 2010 Sep 15.
- Background: PubMed 23607606Chinn IK, Milner JD, Scheinberg P, Douek DC, Markert ML. Thymus transplantation restores the repertoires of forkhead box protein 3 (FoxP3)+ and FoxP3- T cells in complete DiGeorge anomaly. Clin Exp Immunol. 2013 Jul;173(1):140-9. doi: 10.1111/cei.12088.
- Results publication: PubMed 19066739Markert ML, Devlin BH, Chinn IK, McCarthy EA. Thymus transplantation in complete DiGeorge anomaly. Immunol Res. 2009;44(1-3):61-70. doi: 10.1007/s12026-008-8082-5.
- Results publicationMarkert 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.
- Results publication: PubMed 18557726Markert ML, Devlin BH, Chinn IK, McCarthy EA, Li YJ. Factors affecting success of thymus transplantation for complete DiGeorge anomaly. Am J Transplant. 2008 Aug;8(8):1729-36. doi: 10.1111/j.1600-6143.2008.02301.x. Epub 2008 Jun 28.
- Results publication: PubMed 18035553Hudson LL, Louise Markert M, Devlin BH, Haynes BF, Sempowski GD. Human T cell reconstitution in DiGeorge syndrome and HIV-1 infection. Semin Immunol. 2007 Oct;19(5):297-309. doi: 10.1016/j.smim.2007.10.002. Epub 2007 Nov 26.
- Results publication: PubMed 18424759Markert ML, Li J, Devlin BH, Hoehner JC, Rice HE, Skinner MA, Li YJ, Hale LP. Use of allograft biopsies to assess thymopoiesis after thymus transplantation. J Immunol. 2008 May 1;180(9):6354-64. doi: 10.4049/jimmunol.180.9.6354.
- Results publication: PubMed 17284531Markert ML, Devlin BH, Alexieff MJ, Li J, McCarthy EA, Gupton SE, Chinn IK, Hale LP, Kepler TB, He M, Sarzotti M, Skinner MA, Rice HE, Hoehner JC. Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants. Blood. 2007 May 15;109(10):4539-47. doi: 10.1182/blood-2006-10-048652. Epub 2007 Feb 6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
M. Louise Markert, MD, PhD principal investigator
Duke University Medical Center, Pediatrics, Allergy & Immunology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Thymus/Parathyroid Transplantation in people with DiGeorge Syndrome and Hypoparathyroidism, run by Sumitomo Pharma Switzerland GmbH at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy parameter: use of calcium/calcitriol at 1 year post-transplantation. (time frame: 1 year after thymus transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00566488, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2022.