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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Sequential Transplantation of Umbilical Cord Blood Stem Cells and Islet Cells in Children and Adolescents With Monogenic Immunodeficiency Type 1 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 1, Immunologic Deficiency Syndromes

Intervention / Treatment
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* Procedure: Sequential transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.Type 1 diabetes mellitus children with genetic immunodeficiency 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. 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. 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: Mature and effective treatment methods are available. HIV, HBV and HCV were positive. A the active period of infection. At the active stage of malignant tumors. Combination of other fatal diseases. Existence of mental and psychological diseases.

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interventional<br>Sequential transplantation of umbilical cord blood stem cells and islet cells | Procedure: Sequential transplantation<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of serum C-peptide | Islet function (concentration of serum C-peptide) | from the completion of treatment to 3 months | 
| Concentration of serum C-peptide | Islet function (concentration of serum C-peptide) | from the completion of treatment to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of serum C-peptide | Islet function (concentration of serum C-peptide) | from the completion of treatment to 6 months | 
| Concentration of serum C-peptide | Islet function (concentration of serum C-peptide) | from the completion of treatment to 9 months | 
| Concentration of serum C-peptide | Islet function (concentration of serum C-peptide) | from the completion of treatment to 12 months | 
| Concentration of serum C-peptide | Islet function (concentration of serum C-peptide) | from the completion of treatment to 15 months | 
| Concentration of serum C-peptide | Islet function (concentration of serum C-peptide) | from the completion of treatment to 18 months | 
| Concentration of serum C-peptide | Islet function (concentration of serum C-peptide) | from the completion of treatment to 21 months | 
| Concentration of serum C-peptide | Islet function (concentration of serum C-peptide) | from the completion of treatment to 24 months | 
| Concentration of serum C-peptide | Islet function (concentration of serum C-peptide) | from the completion of treatment to 27 months | 
| Concentration of serum C-peptide | Islet function (concentration of serum C-peptide) | from the completion of treatment to 30 months | 
| Concentration of serum C-peptide | Islet function (concentration of serum C-peptide) | from the completion of treatment to 33 months | 
| Concentration of serum insulin | Concentration of serum insulin | from the completion of treatment to 3 months | 
| Concentration of serum insulin | Concentration of serum insulin | from the completion of treatment to 6 months | 
| Concentration of serum insulin | Concentration of serum insulin | from the completion of treatment to 9 months | 
| Concentration of serum insulin | Concentration of serum insulin | from the completion of treatment to 12 months | 
| Concentration of serum insulin | Concentration of serum insulin | from the completion of treatment to 15 months | 
| Concentration of serum insulin | Concentration of serum insulin | from the completion of treatment to 18 months | 
| Concentration of serum insulin | Concentration of serum insulin | from the completion of treatment to 21 months | 
| Concentration of serum insulin | Concentration of serum insulin | from the completion of treatment to 24 months | 
| Concentration of serum insulin | Concentration of serum insulin | from the completion of treatment to 27 months | 
| Concentration of serum insulin | Concentration of serum insulin | from the completion of treatment to 30 months | 
| Concentration of serum insulin | Concentration of serum insulin | from the completion of treatment to 33 months | 
| Concentration of serum insulin | Concentration of serum insulin | from the completion of treatment to 36 months | 
| Fast blood glucose level | Fast blood glucose level | from the completion of treatment to 3 months | 
| Fast blood glucose level | Fast blood glucose level | from the completion of treatment to 6 months | 
| Fast blood glucose level | Fast blood glucose level | from the completion of treatment to 9 months | 
| Fast blood glucose level | Fast blood glucose level | from the completion of treatment to 12 months | 
| Fast blood glucose level | Fast blood glucose level | from the completion of treatment to 15 months | 
| Fast blood glucose level | Fast blood glucose level | from the completion of treatment to 18 months | 
| Fast blood glucose level | Fast blood glucose level | from the completion of treatment to 21 months | 
| Fast blood glucose level | Fast blood glucose level | from the completion of treatment to 24 months | 
| Fast blood glucose level | Fast blood glucose level | from the completion of treatment to 27 months | 
| Fast blood glucose level | Fast blood glucose level | from the completion of treatment to 30 months | 
| Fast blood glucose level | Fast blood glucose level | from the completion of treatment to 33 months | 
| Fast blood glucose level | Fast blood glucose level | from the completion of treatment to 36 months | 
| HbA1c level | HbA1c level | from the completion of treatment to 3 months | 
| HbA1c level | HbA1c level | from the completion of treatment to 6 months | 
| HbA1c level | HbA1c level | from the completion of treatment to 9 months | 
| HbA1c level | HbA1c level | from the completion of treatment to 12 months | 
| HbA1c level | HbA1c level | from the completion of treatment to 15 months | 
| HbA1c level | HbA1c level | from the completion of treatment to 18 months | 
| HbA1c level | HbA1c level | from the completion of treatment to 21 months | 
| HbA1c level | HbA1c level | from the completion of treatment to 24 months | 
| HbA1c level | HbA1c level | from the completion of treatment to 27 months | 
| HbA1c level | HbA1c level | from the completion of treatment to 30 months | 
| HbA1c level | HbA1c level | from the completion of treatment to 33 months | 
| HbA1c level | HbA1c level | from the completion of treatment to 36 months | 
| occurrence of infection (number of infections) | occurrence of infection (number of infections) | from the completion of treatment to 3 months | 
| occurrence of infection (number of infections) | occurrence of infection (number of infections) | from the completion of treatment to 6 months | 
| occurrence of infection (number of infections) | occurrence of infection (number of infections) | from the completion of treatment to 9 months | 
| occurrence of infection (number of infections) | occurrence of infection (number of infections) | from the completion of treatment to 12 months | 
| occurrence of infection (number of infections) | occurrence of infection (number of infections) | from the completion of treatment to 15 months | 
| occurrence of infection (number of infections) | occurrence of infection (number of infections) | from the completion of treatment to 18 months | 
| occurrence of infection (number of infections) | occurrence of infection (number of infections) | from the completion of treatment to 21 months | 
| occurrence of infection (number of infections) | occurrence of infection (number of infections) | from the completion of treatment to 24 months | 
| occurrence of infection (number of infections) | occurrence of infection (number of infections) | from the completion of treatment to 27 months | 
| occurrence of infection (number of infections) | occurrence of infection (number of infections) | from the completion of treatment to 30 months | 
| occurrence of infection (number of infections) | occurrence of infection (number of infections) | from the completion of treatment to 33 months | 
| occurrence of infection (number of infections) | occurrence of infection (number of infections) | from the completion of treatment to 36 months | 
| Concentration of blood immunoglobulin | Concentration of blood immunoglobulin | from the completion of treatment to 3 months | 
| Concentration of blood immunoglobulin | Concentration of blood immunoglobulin | from the completion of treatment to 6 months | 
| Concentration of blood immunoglobulin | Concentration of blood immunoglobulin | from the completion of treatment to 9 months | 
| Concentration of blood immunoglobulin | Concentration of blood immunoglobulin | from the completion of treatment to 12 months | 
| Concentration of blood immunoglobulin | Concentration of blood immunoglobulin | from the completion of treatment to 15 months | 
| Concentration of blood immunoglobulin | Concentration of blood immunoglobulin | from the completion of treatment to 18 months | 
| Concentration of blood immunoglobulin | Concentration of blood immunoglobulin | from the completion of treatment to 21 months | 
| Concentration of blood immunoglobulin | Concentration of blood immunoglobulin | from the completion of treatment to 24 months | 
| Concentration of blood immunoglobulin | Concentration of blood immunoglobulin | from the completion of treatment to 27 months | 
| Concentration of blood immunoglobulin | Concentration of blood immunoglobulin | from the completion of treatment to 30 months | 
| Concentration of blood immunoglobulin | Concentration of blood immunoglobulin | from the completion of treatment to 33 months | 
| Concentration of blood immunoglobulin | Concentration of blood immunoglobulin | from the completion of treatment to 36 months | 
| Concentration of T lymphocyte subsets | Concentration of T lymphocyte subsets | from the completion of treatment to 3 months | 
| Concentration of T lymphocyte subsets | Concentration of T lymphocyte subsets | from the completion of treatment to 6 months | 
| Concentration of T lymphocyte subsets | Concentration of T lymphocyte subsets | from the completion of treatment to 9 months | 
| Concentration of T lymphocyte subsets | Concentration of T lymphocyte subsets | from the completion of treatment to 12 months | 
| Concentration of T lymphocyte subsets | Concentration of T lymphocyte subsets | from the completion of treatment to 15 months | 
| Concentration of T lymphocyte subsets | Concentration of T lymphocyte subsets | from the completion of treatment to 18 months | 
| Concentration of T lymphocyte subsets | Concentration of T lymphocyte subsets | from the completion of treatment to 21 months | 
| Concentration of T lymphocyte subsets | Concentration of T lymphocyte subsets | from the completion of treatment to 24 months | 
| Concentration of T lymphocyte subsets | Concentration of T lymphocyte subsets | from the completion of treatment to 27 months | 
| Concentration of T lymphocyte subsets | Concentration of T lymphocyte subsets | from the completion of treatment to 30 months | 
| Concentration of T lymphocyte subsets | Concentration of T lymphocyte subsets | from the completion of treatment to 33 months | 
| Concentration of T lymphocyte subsets | Concentration of T lymphocyte subsets | from the completion of treatment to 36 months | 
| Concentraion of interleukin-2 | Cytokines (concentraion of interleukin-2) | from the completion of treatment to 3 months | 
| Concentraion of interleukin-2 | Cytokines (concentraion of interleukin-2) | from the completion of treatment to 6 months | 
| Concentraion of interleukin-2 | Cytokines (concentraion of interleukin-2) | from the completion of treatment to 9 months | 
| Concentraion of interleukin-2 | Cytokines (concentraion of interleukin-2) | from the completion of treatment to 12 months | 
| Concentraion of interleukin-2 | Cytokines (concentraion of interleukin-2) | from the completion of treatment to 15 months | 
| Concentraion of interleukin-2 | Cytokines (concentraion of interleukin-2) | from the completion of treatment to 18 months | 
| Concentraion of interleukin-2 | Cytokines (concentraion of interleukin-2) | from the completion of treatment to 21 months | 
| Concentraion of interleukin-2 | Cytokines (concentraion of interleukin-2) | from the completion of treatment to 24 months | 
| Concentraion of interleukin-2 | Cytokines (concentraion of interleukin-2) | from the completion of treatment to 27 months | 
| Concentraion of interleukin-2 | Cytokines (concentraion of interleukin-2) | from the completion of treatment to 30 months | 
| Concentraion of interleukin-2 | Cytokines (concentraion of interleukin-2) | from the completion of treatment to 33 months | 
| Concentraion of interleukin-2 | Cytokines (concentraion of interleukin-2) | from the completion of treatment to 36 months | 
| Body height | Body height | from the completion of treatment to 3 months | 
| Body height | Body height | from the completion of treatment to 6 months | 
| Body height | Body height | from the completion of treatment to 9 months | 
| Body height | Body height | from the completion of treatment to 12 months | 
| Body height | Body height | from the completion of treatment to 15 months | 
| Body height | Body height | from the completion of treatment to 18 months | 
| Body height | Body height | from the completion of treatment to 21 months | 
| Body height | Body height | from the completion of treatment to 24 months | 
| Body height | Body height | from the completion of treatment to 27 months | 
| Body height | Body height | from the completion of treatment to 30 months | 
| Body height | Body height | from the completion of treatment to 33 months | 
| Body height | Body height | from the completion of treatment to 36 months | 
| Body weight | Body weight | from the completion of treatment to 3 months | 
| Body weight | Body weight | from the completion of treatment to 6 months | 
| Body weight | Body weight | from the completion of treatment to 9 months | 
| Body weight | Body weight | from the completion of treatment to 12 months | 
| Body weight | Body weight | from the completion of treatment to 15 months | 
| Body weight | Body weight | from the completion of treatment to 18 months | 
| Body weight | Body weight | from the completion of treatment to 21 months | 
| Body weight | Body weight | from the completion of treatment to 24 months | 
| Body weight | Body weight | from the completion of treatment to 27 months | 
| Body weight | Body weight | from the completion of treatment to 30 months | 
| Body weight | Body weight | from the completion of treatment to 33 months | 
| Body weight | Body weight | from the completion of treatment to 36 months | 
| Tanner stage | Puberty change (Tanner stage) | from the completion of treatment to 3 months | 
| Tanner stage | Puberty change (Tanner stage) | from the completion of treatment to 6 months | 
| Tanner stage | Puberty change (Tanner stage) | from the completion of treatment to 9 months | 
| Tanner stage | Puberty change (Tanner stage) | from the completion of treatment to 12 months | 
| Tanner stage | Puberty change (Tanner stage) | from the completion of treatment to 15 months | 
| Tanner stage | Puberty change (Tanner stage) | from the completion of treatment to 18 months | 
| Tanner stage | Puberty change (Tanner stage) | from the completion of treatment to 21 months | 
| Tanner stage | Puberty change (Tanner stage) | from the completion of treatment to 24 months | 
| Tanner stage | Puberty change (Tanner stage) | from the completion of treatment to 27 months | 
| Tanner stage | Puberty change (Tanner stage) | from the completion of treatment to 30 months | 
| Tanner stage | Puberty change (Tanner stage) | from the completion of treatment to 33 months | 
| Tanner stage | Puberty change (Tanner stage) | from the completion of treatment to 36 months | 
| Occurrence of graft versus host disease | Occurrence of graft versus host disease | from the completion of treatment to 3 months | 
| Occurrence of graft versus host disease | Occurrence of graft versus host disease | from the completion of treatment to 6 months | 
| Occurrence of graft versus host disease | Occurrence of graft versus host disease | from the completion of treatment to 9 months | 
| Occurrence of graft versus host disease | Occurrence of graft versus host disease | from the completion of treatment to 12 months | 
| Occurrence of graft versus host disease | Occurrence of graft versus host disease | from the completion of treatment to 15 months | 
| Occurrence of graft versus host disease | Occurrence of graft versus host disease | from the completion of treatment to 18 months | 
| Occurrence of graft versus host disease | Occurrence of graft versus host disease | from the completion of treatment to 21 months | 
| Occurrence of graft versus host disease | Occurrence of graft versus host disease | from the completion of treatment to 24 months | 
| Occurrence of graft versus host disease | Occurrence of graft versus host disease | from the completion of treatment to 27 months | 
| Occurrence of graft versus host disease | Occurrence of graft versus host disease | from the completion of treatment to 30 months | 
| Occurrence of graft versus host disease | Occurrence of graft versus host disease | from the completion of treatment to 33 months | 
| Occurrence of graft versus host disease | Occurrence of graft versus host disease | from the completion of treatment to 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Islets of Langerhans Transplantation, Cord Blood Stem Cell Transplantation