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Sequential Transplantation of UCBSCs and Islet Cells in Children and Adolescents With Monogenic Immunodeficiency T1DM

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ClinicalTrials.gov Identifier: NCT03835312
Recruitment Status : Not yet recruiting
First Posted : February 8, 2019
Last Update Posted : February 8, 2019
Sponsor:
Information provided by (Responsible Party):
Children's Hospital of Fudan University

Brief Summary:
This study evaluates the efficacy of sequential transplantation of umbilical cord blood stem cells and islet cells in children with monogenic immunodeficiency type 1 diabetes mellitus. Umbilical cord blood stem cell transplantation will be performed first. Children with stable immune reconstruction will than receive islet cell transplantation.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Immunologic Deficiency Syndromes Procedure: Sequential transplantation Not Applicable

Detailed Description:

Monogenic immunodeficiency type 1 diabetes mellitus (T1DM) usually onsets in early age and has a long course of treatment. Because of T cell deficiency, patients are prone to recurrent infection, hemorrhage, sepsis, colitis or complications of diabetes mellitus, which lead to early death.

New clinical treatment schemes have been explored and introduced around the world. Sequential transplantation of umbilical cord blood stem cells and islet cells is the latest treatment method for these children. Early treatment of monogenic immunodeficiency T1DM children can avoid disease-related organ toxicity, infection risk associated with chronic immunosuppression, and possible prevention of autoimmune endocrine organ damage. Thus, sequential transplantation of umbilical cord blood stem cells and islet cells is the only possible cure for those patients currently.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Sequential Transplantation of Umbilical Cord Blood Stem Cells and Islet Cells in Children and Adolescents With Monogenic Immunodeficiency Type 1 Diabetes Mellitus
Estimated Study Start Date : February 20, 2019
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : December 31, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
Experimental: Interventional
Sequential transplantation of umbilical cord blood stem cells and islet cells
Procedure: Sequential transplantation
After successful matching of umbilical cord blood stem cells, patients will receive pretreatment and chemotherapy under protective isolation, followed by thawing and reinfusion of umbilical cord blood stem cells. Immunosuppressive agents will be used for GVHD prevention and anti-infection support will be provided after reinfusion. The status of umbilical cord blood stem cell implantation, immune reconstruction and therapeutic effect will be evaluated. Islet transplantation will be performed in those who meet the conditions. The long-term prognosis will be observed by long-term follow-up.




Primary Outcome Measures :
  1. Concentration of serum C-peptide [ Time Frame: from the completion of treatment to 3 months ]
    Islet function (concentration of serum C-peptide)

  2. Concentration of serum C-peptide [ Time Frame: from the completion of treatment to 3 years ]
    Islet function (concentration of serum C-peptide)


Secondary Outcome Measures :
  1. Concentration of serum C-peptide [ Time Frame: from the completion of treatment to 6 months ]
    Islet function (concentration of serum C-peptide)

  2. Concentration of serum C-peptide [ Time Frame: from the completion of treatment to 9 months ]
    Islet function (concentration of serum C-peptide)

  3. Concentration of serum C-peptide [ Time Frame: from the completion of treatment to 12 months ]
    Islet function (concentration of serum C-peptide)

  4. Concentration of serum C-peptide [ Time Frame: from the completion of treatment to 15 months ]
    Islet function (concentration of serum C-peptide)

  5. Concentration of serum C-peptide [ Time Frame: from the completion of treatment to 18 months ]
    Islet function (concentration of serum C-peptide)

  6. Concentration of serum C-peptide [ Time Frame: from the completion of treatment to 21 months ]
    Islet function (concentration of serum C-peptide)

  7. Concentration of serum C-peptide [ Time Frame: from the completion of treatment to 24 months ]
    Islet function (concentration of serum C-peptide)

  8. Concentration of serum C-peptide [ Time Frame: from the completion of treatment to 27 months ]
    Islet function (concentration of serum C-peptide)

  9. Concentration of serum C-peptide [ Time Frame: from the completion of treatment to 30 months ]
    Islet function (concentration of serum C-peptide)

  10. Concentration of serum C-peptide [ Time Frame: from the completion of treatment to 33 months ]
    Islet function (concentration of serum C-peptide)

  11. Concentration of serum insulin [ Time Frame: from the completion of treatment to 3 months ]
    Concentration of serum insulin

  12. Concentration of serum insulin [ Time Frame: from the completion of treatment to 6 months ]
    Concentration of serum insulin

  13. Concentration of serum insulin [ Time Frame: from the completion of treatment to 9 months ]
    Concentration of serum insulin

  14. Concentration of serum insulin [ Time Frame: from the completion of treatment to 12 months ]
    Concentration of serum insulin

  15. Concentration of serum insulin [ Time Frame: from the completion of treatment to 15 months ]
    Concentration of serum insulin

  16. Concentration of serum insulin [ Time Frame: from the completion of treatment to 18 months ]
    Concentration of serum insulin

  17. Concentration of serum insulin [ Time Frame: from the completion of treatment to 21 months ]
    Concentration of serum insulin

  18. Concentration of serum insulin [ Time Frame: from the completion of treatment to 24 months ]
    Concentration of serum insulin

  19. Concentration of serum insulin [ Time Frame: from the completion of treatment to 27 months ]
    Concentration of serum insulin

  20. Concentration of serum insulin [ Time Frame: from the completion of treatment to 30 months ]
    Concentration of serum insulin

  21. Concentration of serum insulin [ Time Frame: from the completion of treatment to 33 months ]
    Concentration of serum insulin

  22. Concentration of serum insulin [ Time Frame: from the completion of treatment to 36 months ]
    Concentration of serum insulin

  23. Fast blood glucose level [ Time Frame: from the completion of treatment to 3 months ]
    Fast blood glucose level

  24. Fast blood glucose level [ Time Frame: from the completion of treatment to 6 months ]
    Fast blood glucose level

  25. Fast blood glucose level [ Time Frame: from the completion of treatment to 9 months ]
    Fast blood glucose level

  26. Fast blood glucose level [ Time Frame: from the completion of treatment to 12 months ]
    Fast blood glucose level

  27. Fast blood glucose level [ Time Frame: from the completion of treatment to 15 months ]
    Fast blood glucose level

  28. Fast blood glucose level [ Time Frame: from the completion of treatment to 18 months ]
    Fast blood glucose level

  29. Fast blood glucose level [ Time Frame: from the completion of treatment to 21 months ]
    Fast blood glucose level

  30. Fast blood glucose level [ Time Frame: from the completion of treatment to 24 months ]
    Fast blood glucose level

  31. Fast blood glucose level [ Time Frame: from the completion of treatment to 27 months ]
    Fast blood glucose level

  32. Fast blood glucose level [ Time Frame: from the completion of treatment to 30 months ]
    Fast blood glucose level

  33. Fast blood glucose level [ Time Frame: from the completion of treatment to 33 months ]
    Fast blood glucose level

  34. Fast blood glucose level [ Time Frame: from the completion of treatment to 36 months ]
    Fast blood glucose level

  35. HbA1c level [ Time Frame: from the completion of treatment to 3 months ]
    HbA1c level

  36. HbA1c level [ Time Frame: from the completion of treatment to 6 months ]
    HbA1c level

  37. HbA1c level [ Time Frame: from the completion of treatment to 9 months ]
    HbA1c level

  38. HbA1c level [ Time Frame: from the completion of treatment to 12 months ]
    HbA1c level

  39. HbA1c level [ Time Frame: from the completion of treatment to 15 months ]
    HbA1c level

  40. HbA1c level [ Time Frame: from the completion of treatment to 18 months ]
    HbA1c level

  41. HbA1c level [ Time Frame: from the completion of treatment to 21 months ]
    HbA1c level

  42. HbA1c level [ Time Frame: from the completion of treatment to 24 months ]
    HbA1c level

  43. HbA1c level [ Time Frame: from the completion of treatment to 27 months ]
    HbA1c level

  44. HbA1c level [ Time Frame: from the completion of treatment to 30 months ]
    HbA1c level

  45. HbA1c level [ Time Frame: from the completion of treatment to 33 months ]
    HbA1c level

  46. HbA1c level [ Time Frame: from the completion of treatment to 36 months ]
    HbA1c level

  47. occurrence of infection (number of infections) [ Time Frame: from the completion of treatment to 3 months ]
    occurrence of infection (number of infections)

  48. occurrence of infection (number of infections) [ Time Frame: from the completion of treatment to 6 months ]
    occurrence of infection (number of infections)

  49. occurrence of infection (number of infections) [ Time Frame: from the completion of treatment to 9 months ]
    occurrence of infection (number of infections)

  50. occurrence of infection (number of infections) [ Time Frame: from the completion of treatment to 12 months ]
    occurrence of infection (number of infections)

  51. occurrence of infection (number of infections) [ Time Frame: from the completion of treatment to 15 months ]
    occurrence of infection (number of infections)

  52. occurrence of infection (number of infections) [ Time Frame: from the completion of treatment to 18 months ]
    occurrence of infection (number of infections)

  53. occurrence of infection (number of infections) [ Time Frame: from the completion of treatment to 21 months ]
    occurrence of infection (number of infections)

  54. occurrence of infection (number of infections) [ Time Frame: from the completion of treatment to 24 months ]
    occurrence of infection (number of infections)

  55. occurrence of infection (number of infections) [ Time Frame: from the completion of treatment to 27 months ]
    occurrence of infection (number of infections)

  56. occurrence of infection (number of infections) [ Time Frame: from the completion of treatment to 30 months ]
    occurrence of infection (number of infections)

  57. occurrence of infection (number of infections) [ Time Frame: from the completion of treatment to 33 months ]
    occurrence of infection (number of infections)

  58. occurrence of infection (number of infections) [ Time Frame: from the completion of treatment to 36 months ]
    occurrence of infection (number of infections)

  59. Concentration of blood immunoglobulin [ Time Frame: from the completion of treatment to 3 months ]
    Concentration of blood immunoglobulin

  60. Concentration of blood immunoglobulin [ Time Frame: from the completion of treatment to 6 months ]
    Concentration of blood immunoglobulin

  61. Concentration of blood immunoglobulin [ Time Frame: from the completion of treatment to 9 months ]
    Concentration of blood immunoglobulin

  62. Concentration of blood immunoglobulin [ Time Frame: from the completion of treatment to 12 months ]
    Concentration of blood immunoglobulin

  63. Concentration of blood immunoglobulin [ Time Frame: from the completion of treatment to 15 months ]
    Concentration of blood immunoglobulin

  64. Concentration of blood immunoglobulin [ Time Frame: from the completion of treatment to 18 months ]
    Concentration of blood immunoglobulin

  65. Concentration of blood immunoglobulin [ Time Frame: from the completion of treatment to 21 months ]
    Concentration of blood immunoglobulin

  66. Concentration of blood immunoglobulin [ Time Frame: from the completion of treatment to 24 months ]
    Concentration of blood immunoglobulin

  67. Concentration of blood immunoglobulin [ Time Frame: from the completion of treatment to 27 months ]
    Concentration of blood immunoglobulin

  68. Concentration of blood immunoglobulin [ Time Frame: from the completion of treatment to 30 months ]
    Concentration of blood immunoglobulin

  69. Concentration of blood immunoglobulin [ Time Frame: from the completion of treatment to 33 months ]
    Concentration of blood immunoglobulin

  70. Concentration of blood immunoglobulin [ Time Frame: from the completion of treatment to 36 months ]
    Concentration of blood immunoglobulin

  71. Concentration of T lymphocyte subsets [ Time Frame: from the completion of treatment to 3 months ]
    Concentration of T lymphocyte subsets

  72. Concentration of T lymphocyte subsets [ Time Frame: from the completion of treatment to 6 months ]
    Concentration of T lymphocyte subsets

  73. Concentration of T lymphocyte subsets [ Time Frame: from the completion of treatment to 9 months ]
    Concentration of T lymphocyte subsets

  74. Concentration of T lymphocyte subsets [ Time Frame: from the completion of treatment to 12 months ]
    Concentration of T lymphocyte subsets

  75. Concentration of T lymphocyte subsets [ Time Frame: from the completion of treatment to 15 months ]
    Concentration of T lymphocyte subsets

  76. Concentration of T lymphocyte subsets [ Time Frame: from the completion of treatment to 18 months ]
    Concentration of T lymphocyte subsets

  77. Concentration of T lymphocyte subsets [ Time Frame: from the completion of treatment to 21 months ]
    Concentration of T lymphocyte subsets

  78. Concentration of T lymphocyte subsets [ Time Frame: from the completion of treatment to 24 months ]
    Concentration of T lymphocyte subsets

  79. Concentration of T lymphocyte subsets [ Time Frame: from the completion of treatment to 27 months ]
    Concentration of T lymphocyte subsets

  80. Concentration of T lymphocyte subsets [ Time Frame: from the completion of treatment to 30 months ]
    Concentration of T lymphocyte subsets

  81. Concentration of T lymphocyte subsets [ Time Frame: from the completion of treatment to 33 months ]
    Concentration of T lymphocyte subsets

  82. Concentration of T lymphocyte subsets [ Time Frame: from the completion of treatment to 36 months ]
    Concentration of T lymphocyte subsets

  83. Concentraion of interleukin-2 [ Time Frame: from the completion of treatment to 3 months ]
    Cytokines (concentraion of interleukin-2)

  84. Concentraion of interleukin-2 [ Time Frame: from the completion of treatment to 6 months ]
    Cytokines (concentraion of interleukin-2)

  85. Concentraion of interleukin-2 [ Time Frame: from the completion of treatment to 9 months ]
    Cytokines (concentraion of interleukin-2)

  86. Concentraion of interleukin-2 [ Time Frame: from the completion of treatment to 12 months ]
    Cytokines (concentraion of interleukin-2)

  87. Concentraion of interleukin-2 [ Time Frame: from the completion of treatment to 15 months ]
    Cytokines (concentraion of interleukin-2)

  88. Concentraion of interleukin-2 [ Time Frame: from the completion of treatment to 18 months ]
    Cytokines (concentraion of interleukin-2)

  89. Concentraion of interleukin-2 [ Time Frame: from the completion of treatment to 21 months ]
    Cytokines (concentraion of interleukin-2)

  90. Concentraion of interleukin-2 [ Time Frame: from the completion of treatment to 24 months ]
    Cytokines (concentraion of interleukin-2)

  91. Concentraion of interleukin-2 [ Time Frame: from the completion of treatment to 27 months ]
    Cytokines (concentraion of interleukin-2)

  92. Concentraion of interleukin-2 [ Time Frame: from the completion of treatment to 30 months ]
    Cytokines (concentraion of interleukin-2)

  93. Concentraion of interleukin-2 [ Time Frame: from the completion of treatment to 33 months ]
    Cytokines (concentraion of interleukin-2)

  94. Concentraion of interleukin-2 [ Time Frame: from the completion of treatment to 36 months ]
    Cytokines (concentraion of interleukin-2)

  95. Body height [ Time Frame: from the completion of treatment to 3 months ]
    Body height

  96. Body height [ Time Frame: from the completion of treatment to 6 months ]
    Body height

  97. Body height [ Time Frame: from the completion of treatment to 9 months ]
    Body height

  98. Body height [ Time Frame: from the completion of treatment to 12 months ]
    Body height

  99. Body height [ Time Frame: from the completion of treatment to 15 months ]
    Body height

  100. Body height [ Time Frame: from the completion of treatment to 18 months ]
    Body height

  101. Body height [ Time Frame: from the completion of treatment to 21 months ]
    Body height

  102. Body height [ Time Frame: from the completion of treatment to 24 months ]
    Body height

  103. Body height [ Time Frame: from the completion of treatment to 27 months ]
    Body height

  104. Body height [ Time Frame: from the completion of treatment to 30 months ]
    Body height

  105. Body height [ Time Frame: from the completion of treatment to 33 months ]
    Body height

  106. Body height [ Time Frame: from the completion of treatment to 36 months ]
    Body height

  107. Body weight [ Time Frame: from the completion of treatment to 3 months ]
    Body weight

  108. Body weight [ Time Frame: from the completion of treatment to 6 months ]
    Body weight

  109. Body weight [ Time Frame: from the completion of treatment to 9 months ]
    Body weight

  110. Body weight [ Time Frame: from the completion of treatment to 12 months ]
    Body weight

  111. Body weight [ Time Frame: from the completion of treatment to 15 months ]
    Body weight

  112. Body weight [ Time Frame: from the completion of treatment to 18 months ]
    Body weight

  113. Body weight [ Time Frame: from the completion of treatment to 21 months ]
    Body weight

  114. Body weight [ Time Frame: from the completion of treatment to 24 months ]
    Body weight

  115. Body weight [ Time Frame: from the completion of treatment to 27 months ]
    Body weight

  116. Body weight [ Time Frame: from the completion of treatment to 30 months ]
    Body weight

  117. Body weight [ Time Frame: from the completion of treatment to 33 months ]
    Body weight

  118. Body weight [ Time Frame: from the completion of treatment to 36 months ]
    Body weight

  119. Tanner stage [ Time Frame: from the completion of treatment to 3 months ]
    Puberty change (Tanner stage)

  120. Tanner stage [ Time Frame: from the completion of treatment to 6 months ]
    Puberty change (Tanner stage)

  121. Tanner stage [ Time Frame: from the completion of treatment to 9 months ]
    Puberty change (Tanner stage)

  122. Tanner stage [ Time Frame: from the completion of treatment to 12 months ]
    Puberty change (Tanner stage)

  123. Tanner stage [ Time Frame: from the completion of treatment to 15 months ]
    Puberty change (Tanner stage)

  124. Tanner stage [ Time Frame: from the completion of treatment to 18 months ]
    Puberty change (Tanner stage)

  125. Tanner stage [ Time Frame: from the completion of treatment to 21 months ]
    Puberty change (Tanner stage)

  126. Tanner stage [ Time Frame: from the completion of treatment to 24 months ]
    Puberty change (Tanner stage)

  127. Tanner stage [ Time Frame: from the completion of treatment to 27 months ]
    Puberty change (Tanner stage)

  128. Tanner stage [ Time Frame: from the completion of treatment to 30 months ]
    Puberty change (Tanner stage)

  129. Tanner stage [ Time Frame: from the completion of treatment to 33 months ]
    Puberty change (Tanner stage)

  130. Tanner stage [ Time Frame: from the completion of treatment to 36 months ]
    Puberty change (Tanner stage)

  131. Occurrence of graft versus host disease [ Time Frame: from the completion of treatment to 3 months ]
    Occurrence of graft versus host disease

  132. Occurrence of graft versus host disease [ Time Frame: from the completion of treatment to 6 months ]
    Occurrence of graft versus host disease

  133. Occurrence of graft versus host disease [ Time Frame: from the completion of treatment to 9 months ]
    Occurrence of graft versus host disease

  134. Occurrence of graft versus host disease [ Time Frame: from the completion of treatment to 12 months ]
    Occurrence of graft versus host disease

  135. Occurrence of graft versus host disease [ Time Frame: from the completion of treatment to 15 months ]
    Occurrence of graft versus host disease

  136. Occurrence of graft versus host disease [ Time Frame: from the completion of treatment to 18 months ]
    Occurrence of graft versus host disease

  137. Occurrence of graft versus host disease [ Time Frame: from the completion of treatment to 21 months ]
    Occurrence of graft versus host disease

  138. Occurrence of graft versus host disease [ Time Frame: from the completion of treatment to 24 months ]
    Occurrence of graft versus host disease

  139. Occurrence of graft versus host disease [ Time Frame: from the completion of treatment to 27 months ]
    Occurrence of graft versus host disease

  140. Occurrence of graft versus host disease [ Time Frame: from the completion of treatment to 30 months ]
    Occurrence of graft versus host disease

  141. Occurrence of graft versus host disease [ Time Frame: from the completion of treatment to 33 months ]
    Occurrence of graft versus host disease

  142. Occurrence of graft versus host disease [ Time Frame: from the completion of treatment to 36 months ]
    Occurrence of graft versus host disease



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

1.Type 1 diabetes mellitus children with genetic immunodeficiency

  1. Meet the diagnostic criteria of type 1 diabetes mellitus: clinical manifestations of typical diabetes mellitus include polyphagia, polyuria, weight loss, or diabetic ketoacidosis, confirmed by blood sugar level, islet function and autoimmune antibody.
  2. Existence of extrapancreatic organ damage: (1) inflammatory bowel disease, (2) impairment of renal function, (3) repeated infection of mouth, skin, anus or whole body, (4) immune hepatitis, (5) persistent chronic immune iridocyclitis, (6) immune adrenalinitis leading to adrenocortical dysfunction, (7) pituitary inflammation leading to hypophysis, (8) rheumatoid disease, (9) immune vasculitis, (10) systemic lupus erythematosus, (11) other organs besides thyroid function damage. Suffering from one or more of above diseases. Recurrence after receiving regular clinical treatment, including symptomatic treatment of organ protective drugs.
  3. Gene mutation was found according to gene diagnosis: gene mutation was found by gene sequencing. Literature searches at home and abroad confirmed that the defect of the gene resulted in autoimmune or immune dysfunction, resulting in multiple organ dysfunction and poor prognosis.

Exclusion Criteria:

  1. Mature and effective treatment methods are available.
  2. HIV, HBV and HCV were positive.
  3. A the active period of infection.
  4. At the active stage of malignant tumors.
  5. Combination of other fatal diseases.
  6. Existence of mental and psychological diseases.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03835312


Contacts
Contact: Luo Feihong +862164931226 ext +862164931226 luofh@fudan.edu.cn
Contact: Xu Zhenran +862164931226 ext +862164931226 xu_zhenran@163.com

Locations
China, Shanghai
Children's Hospital of Fudan University Recruiting
Shanghai, Shanghai, China
Contact: Luo Feihong    +862164931226 ext +862164931226    luofh@fudan.edu.cn   
Contact: Xu Zhenran    +862164931226 ext +862164931226    xu_zhenran@fudan.edu.cn   
Sponsors and Collaborators
Children's Hospital of Fudan University
Investigators
Study Chair: Luo Feihong Children's Hospital of Fudan University
  Study Documents (Full-Text)

Documents provided by Children's Hospital of Fudan University:
Study Protocol  [PDF] October 16, 2018
Informed Consent Form  [PDF] October 16, 2018
Statistical Analysis Plan  [PDF] October 16, 2018


Publications:

Responsible Party: Children's Hospital of Fudan University
ClinicalTrials.gov Identifier: NCT03835312     History of Changes
Other Study ID Numbers: SeqTranUCBC&IC-001
First Posted: February 8, 2019    Key Record Dates
Last Update Posted: February 8, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Children's Hospital of Fudan University:
Islets of Langerhans Transplantation
Cord Blood Stem Cell Transplantation

Additional relevant MeSH terms:
Diabetes Mellitus
Immunologic Deficiency Syndromes
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Immune System Diseases
Autoimmune Diseases