NCT00576836已完成2 期
Dose Study of Thymus Transplantation in DiGeorge Anomaly, IND 9836, #932.1
适应症
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 2
- 主要终点
- Survival at 1 Year Post-CTTI
研究概览
简要总结
One purpose of this study is to determine whether the amount of cultured thymus tissue implanted into DiGeorge anomaly infants has any effect on the immune outcome. Another purpose of this study is to determine whether parental parathyroid transplantation (in addition to cultured thymus tissue implantation (CTTI) can help both the immune and the calcium problems in DiGeorge infants with hypocalcemia. [Funding Source - FDA Office of Orphan Products Development (OOPD)]
详细描述
DiGeorge anomaly is a congenital disorder in which infants are born with defects of the thymus, heart, and parathyroid gland. Complete DiGeorge Anomaly is usually fatal within the first two years of life. This trial evaluates the role of cultured thymus tissue dose in cultured thymus tissue implantation (CTTI) in complete (typical) DiGeorge anomaly infants, and continues safety assessments.
DiGeorge infants who have successful CTTIs but remain with hypoparathyroidism must go to the clinic for frequent calcium levels and to the hospital for calcium infusions; these infants are at risk for seizures from low calcium. Approximately ½ of infants with profound hypoparathyroidism will develop nephrocalcinosis. This protocol had a parental parathyroid transplant arm for complete DiGeorge infants with athymia and profound hypoparathyroidism.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A parent or guardian of the DGS subject signed the consent form.
- •Medical screening was completed.
- •For a diagnosis of DGS, the subject had to have one of the following:
- •Congenital heart disease;
- •Hypocalcemia requiring replacement;
- •22q11.2 hemizygosity or 10p13 hemizygosity;
- •CHARGE association or CHD7 mutation;
- •A subject with abnormal ears whose mother had diabetes (type I, type II, or gestational).
- •To meet the criteria of typical complete DiGeorge Anomaly (cDGA), the subject had to have either:
- •Circulating CD3+ T cell count by flow cytometry < 50/mm3 OR
- •Circulating CD3+ T cells that were also positive for Cluster of Differentiation 45RA (CD45RA)+ CD62L+ and were < 50/mm3 or less than 5% of total T cells.
- •Thymus Transplant
排除标准
- •Had heart surgery less than 4 weeks prior to projected implant date;
- •Heart surgery anticipated within 3 months after the proposed time of implantation;
- •Present or past lymphadenopathy;
- •Rash associated with T cell infiltration of the dermis and epidermis;
- •Rejection by the surgeon or anesthesiologist as surgical candidate;
- •Lack of sufficient muscle tissue to accept a transplant of 4 g/m2 body surface area (BSA) or 0.2 g/kg subject bodyweight;
- •Had human immunodeficiency virus (HIV) infection;
- •Had prior attempts at immune reconstitution, such as bone marrow transplant or previous thymus transplantation;
- •Ventilator support or positive pressure support: Subjects had to be off ventilator or other pressure support such as continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BiPAP) support for 2 weeks prior to enrollment. If the subject was enrolled and was placed back on ventilator or pressure support, the subject had to be able to be weaned off and remain off ventilator or pressure support for 2 weeks. If the subject could not be successfully weaned off ventilator or pressure support, the subject was to be withdrawn from the study.
- •Additional Inclusion Criteria for Parathyroid Transplant Recipient:
- •2 tests in patient showing: intact parathyroid hormone (PTH) < 5 pg/ml when ionized calcium < 1.1 mmol/L
- •All inclusion criteria for thymus transplant must be met
- •2 involved parents
- •Exclusion for Parathyroid Transplant Recipient:
- •Parents do not meet enrollment criteria.
- •Parent(s) decline to be parathyroid donor(s).
- •Parental Parathyroid Donor Inclusion:
- •> 18 years old
- •Answers all questionnaire items and meets safety screening criteria
- •Normal serum calcium
- •Normal PTH function
- •HLA typing consistent with parentage
- •Parent chosen for donation will share HLA-DR allele in thymus donor; if not applicable, then either parent will be selected (if meet all other criteria).
- •Must not be on anticoagulation or can come off for donation/transplantation
- •Parental Parathyroid Donor Exclusion:
- •Donor is only living involved parent or caretaker of the recipient
- •Hypoparathyroidism - low parathyroid hormone (PTH) in presence of low serum calcium and high serum phosphate
- •Hyperparathyroidism (or history of) - elevated PTH in presence of high serum calcium and low serum phosphate
- •History of cancer
- •Evidence of any of following: HIV-1, HIV-2, HTLV-1, HTLV-2, syphilis, hepatitis B, hepatitis C, West Nile virus, or Trypanosoma Cruzi (Chagas disease)
- •Elevated AST, ALT, alkaline phosphatase > 3 times upper limit of normal
- •History including receipt of a xenograft or risk factors for SARS, Mad Cow - Disease or smallpox. Note: if parent has Mad Cow Disease risk factors (but not active disease), parent(s) may give permission for transplantation.
- •CMV positive urine
- •Positive CMV IgM antibodies
- •Positive IgM anti-EBV VCA
- •On blood thinners and cannot stop for the parathyroid donation
- •Elevated PT or PTT (> ULN)
- •Platelets < 100,000
- •Positive Toxoplasma IgM
- •The donor will receive a history and physical; may be excluded based on PI's medical judgment
- •Hemoglobin < 9 g/dl
- •Infectious lesion on head or neck
- •Goiter on ultrasound
- •Abnormal fiberoptic laryngoscopy of vocal cords
- •Pregnancy
- •Positive HSV IgG is not an exclusion; however, post transplantation prophylaxis is needed
- •Positive VZV IgG is not an exclusion; however, post transplantation prophylaxis is needed
- •Medical concern of otolaryngologist
- •Concern by medical psychologist or social worker. Parents are interviewed together and separately regarding following areas: medical history; health habits; substance use; relationships and support; education/work history; mental status/psychological history; readiness for donation.
- •Questionnaire (safety screening) responses can lead to exclusion.
- 另有 3 项未显示
结局指标
主要结局
Survival at 1 Year Post-CTTI
时间窗: 1 year post-CTTI
Survival at 1 year post CTTI was assessed using the Kaplan Meier Estimated Survival. This mathematical function estimates the survival for a certain length of time.
次要结局
- Immune Reconstitution Efficacy - CD4 T Cells(1 year post-CTTI)
- Immune Reconstitution Efficacy - Naive CD4 T Cells(1 year post-CTTI)
- Immune Reconstitution Efficacy - Naive CD8 T Cells(1 year post-CTTI)
- Immune Reconstitution Efficacy - Response to Mitogens(1 year post-CTTI)
- Thymus Allograft Biopsy(2 to 3 months post-CTTI)
- Immune Reconstitution Efficacy - CD8 T Cells(1 year post-CTTI)
- Immune Reconstitution Efficacy - CD3 T Cells(1 year post-CTTI)
- Survival at 2 Years Post-CTTI(2 years post-CTTI)
研究者
研究点 (2)
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