Clinical trial NCT03835312: Sequential Transplantation of UCBSCs and Islet Cells in Children and Adolescents With Monogenic Immunodeficiency T1DM
Official title: Sequential Transplantation of Umbilical Cord Blood Stem Cells and Islet Cells in Children and Adolescents With Monogenic Immunodeficiency Type 1 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Diabetes Mellitus, Type 1
Immunologic Deficiency Syndromes
Keywords: Islets of Langerhans Transplantation
Cord Blood Stem Cell Transplantation
Lead sponsor: Children's Hospital of Fudan University
Sponsor class: OTHER
First posted: 2019-02-08
Enrollment: 50
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Concentration of serum C-peptide
timeFrame: from the completion of treatment to 3 months
measure: Concentration of serum C-peptide
timeFrame: from the completion of treatment to 3 years
Secondary outcomes:
measure: Concentration of serum C-peptide
timeFrame: from the completion of treatment to 6 months
measure: Concentration of serum C-peptide
timeFrame: from the completion of treatment to 9 months
measure: Concentration of serum C-peptide
timeFrame: from the completion of treatment to 12 months
measure: Concentration of serum C-peptide
timeFrame: from the completion of treatment to 15 months
measure: Concentration of serum C-peptide
timeFrame: from the completion of treatment to 18 months
measure: Concentration of serum C-peptide
timeFrame: from the completion of treatment to 21 months
measure: Concentration of serum C-peptide
timeFrame: from the completion of treatment to 24 months
measure: Concentration of serum C-peptide
timeFrame: from the completion of treatment to 27 months
measure: Concentration of serum C-peptide
timeFrame: from the completion of treatment to 30 months
measure: Concentration of serum C-peptide
timeFrame: from the completion of treatment to 33 months
measure: Concentration of serum insulin
timeFrame: from the completion of treatment to 3 months
measure: Concentration of serum insulin
timeFrame: from the completion of treatment to 6 months
measure: Concentration of serum insulin
timeFrame: from the completion of treatment to 9 months
measure: Concentration of serum insulin
timeFrame: from the completion of treatment to 12 months
measure: Concentration of serum insulin
timeFrame: from the completion of treatment to 15 months
measure: Concentration of serum insulin
timeFrame: from the completion of treatment to 18 months
measure: Concentration of serum insulin
timeFrame: from the completion of treatment to 21 months
measure: Concentration of serum insulin
timeFrame: from the completion of treatment to 24 months
measure: Concentration of serum insulin
timeFrame: from the completion of treatment to 27 months
measure: Concentration of serum insulin
timeFrame: from the completion of treatment to 30 months
measure: Concentration of serum insulin
timeFrame: from the completion of treatment to 33 months
measure: Concentration of serum insulin
timeFrame: from the completion of treatment to 36 months
measure: Fast blood glucose level
timeFrame: from the completion of treatment to 3 months
measure: Fast blood glucose level
timeFrame: from the completion of treatment to 6 months
measure: Fast blood glucose level
timeFrame: from the completion of treatment to 9 months
measure: Fast blood glucose level
timeFrame: from the completion of treatment to 12 months
measure: Fast blood glucose level
timeFrame: from the completion of treatment to 15 months
measure: Fast blood glucose level
timeFrame: from the completion of treatment to 18 months
measure: Fast blood glucose level
timeFrame: from the completion of treatment to 21 months
measure: Fast blood glucose level
timeFrame: from the completion of treatment to 24 months
measure: Fast blood glucose level
timeFrame: from the completion of treatment to 27 months
measure: Fast blood glucose level
timeFrame: from the completion of treatment to 30 months
measure: Fast blood glucose level
timeFrame: from the completion of treatment to 33 months
measure: Fast blood glucose level
timeFrame: from the completion of treatment to 36 months
measure: HbA1c level
timeFrame: from the completion of treatment to 3 months
measure: HbA1c level
timeFrame: from the completion of treatment to 6 months
measure: HbA1c level
timeFrame: from the completion of treatment to 9 months
measure: HbA1c level
timeFrame: from the completion of treatment to 12 months
measure: HbA1c level
timeFrame: from the completion of treatment to 15 months
measure: HbA1c level
timeFrame: from the completion of treatment to 18 months
measure: HbA1c level
timeFrame: from the completion of treatment to 21 months
measure: HbA1c level
timeFrame: from the completion of treatment to 24 months
measure: HbA1c level
timeFrame: from the completion of treatment to 27 months
measure: HbA1c level
timeFrame: from the completion of treatment to 30 months
measure: HbA1c level
timeFrame: from the completion of treatment to 33 months
measure: HbA1c level
timeFrame: from the completion of treatment to 36 months
measure: occurrence of infection (number of infections)
timeFrame: from the completion of treatment to 3 months
measure: occurrence of infection (number of infections)
timeFrame: from the completion of treatment to 6 months
measure: occurrence of infection (number of infections)
timeFrame: from the completion of treatment to 9 months
measure: occurrence of infection (number of infections)
timeFrame: from the completion of treatment to 12 months
measure: occurrence of infection (number of infections)
timeFrame: from the completion of treatment to 15 months
measure: occurrence of infection (number of infections)
timeFrame: from the completion of treatment to 18 months
measure: occurrence of infection (number of infections)
timeFrame: from the completion of treatment to 21 months
measure: occurrence of infection (number of infections)
timeFrame: from the completion of treatment to 24 months
measure: occurrence of infection (number of infections)
timeFrame: from the completion of treatment to 27 months
measure: occurrence of infection (number of infections)
timeFrame: from the completion of treatment to 30 months
measure: occurrence of infection (number of infections)
timeFrame: from the completion of treatment to 33 months
measure: occurrence of infection (number of infections)
timeFrame: from the completion of treatment to 36 months
measure: Concentration of blood immunoglobulin
timeFrame: from the completion of treatment to 3 months
measure: Concentration of blood immunoglobulin
timeFrame: from the completion of treatment to 6 months
measure: Concentration of blood immunoglobulin
timeFrame: from the completion of treatment to 9 months
measure: Concentration of blood immunoglobulin
timeFrame: from the completion of treatment to 12 months
measure: Concentration of blood immunoglobulin
timeFrame: from the completion of treatment to 15 months
measure: Concentration of blood immunoglobulin
timeFrame: from the completion of treatment to 18 months
measure: Concentration of blood immunoglobulin
timeFrame: from the completion of treatment to 21 months
measure: Concentration of blood immunoglobulin
timeFrame: from the completion of treatment to 24 months
measure: Concentration of blood immunoglobulin
timeFrame: from the completion of treatment to 27 months
measure: Concentration of blood immunoglobulin
timeFrame: from the completion of treatment to 30 months
measure: Concentration of blood immunoglobulin
timeFrame: from the completion of treatment to 33 months
measure: Concentration of blood immunoglobulin
timeFrame: from the completion of treatment to 36 months
measure: Concentration of T lymphocyte subsets
timeFrame: from the completion of treatment to 3 months
measure: Concentration of T lymphocyte subsets
timeFrame: from the completion of treatment to 6 months
measure: Concentration of T lymphocyte subsets
timeFrame: from the completion of treatment to 9 months
measure: Concentration of T lymphocyte subsets
timeFrame: from the completion of treatment to 12 months
measure: Concentration of T lymphocyte subsets
timeFrame: from the completion of treatment to 15 months
measure: Concentration of T lymphocyte subsets
timeFrame: from the completion of treatment to 18 months
measure: Concentration of T lymphocyte subsets
timeFrame: from the completion of treatment to 21 months
measure: Concentration of T lymphocyte subsets
timeFrame: from the completion of treatment to 24 months
measure: Concentration of T lymphocyte subsets
timeFrame: from the completion of treatment to 27 months
measure: Concentration of T lymphocyte subsets
timeFrame: from the completion of treatment to 30 months
measure: Concentration of T lymphocyte subsets
timeFrame: from the completion of treatment to 33 months
measure: Concentration of T lymphocyte subsets
timeFrame: from the completion of treatment to 36 months
measure: Concentraion of interleukin-2
timeFrame: from the completion of treatment to 3 months
measure: Concentraion of interleukin-2
timeFrame: from the completion of treatment to 6 months
measure: Concentraion of interleukin-2
timeFrame: from the completion of treatment to 9 months
measure: Concentraion of interleukin-2
timeFrame: from the completion of treatment to 12 months
measure: Concentraion of interleukin-2
timeFrame: from the completion of treatment to 15 months
measure: Concentraion of interleukin-2
timeFrame: from the completion of treatment to 18 months
measure: Concentraion of interleukin-2
timeFrame: from the completion of treatment to 21 months
measure: Concentraion of interleukin-2
timeFrame: from the completion of treatment to 24 months
measure: Concentraion of interleukin-2
timeFrame: from the completion of treatment to 27 months
measure: Concentraion of interleukin-2
timeFrame: from the completion of treatment to 30 months
measure: Concentraion of interleukin-2
timeFrame: from the completion of treatment to 33 months
measure: Concentraion of interleukin-2
timeFrame: from the completion of treatment to 36 months
measure: Body height
timeFrame: from the completion of treatment to 3 months
measure: Body height
timeFrame: from the completion of treatment to 6 months
measure: Body height
timeFrame: from the completion of treatment to 9 months
measure: Body height
timeFrame: from the completion of treatment to 12 months
measure: Body height
timeFrame: from the completion of treatment to 15 months
measure: Body height
timeFrame: from the completion of treatment to 18 months
measure: Body height
timeFrame: from the completion of treatment to 21 months
measure: Body height
timeFrame: from the completion of treatment to 24 months
measure: Body height
timeFrame: from the completion of treatment to 27 months
measure: Body height
timeFrame: from the completion of treatment to 30 months
measure: Body height
timeFrame: from the completion of treatment to 33 months
measure: Body height
timeFrame: from the completion of treatment to 36 months
measure: Body weight
timeFrame: from the completion of treatment to 3 months
measure: Body weight
timeFrame: from the completion of treatment to 6 months
measure: Body weight
timeFrame: from the completion of treatment to 9 months
measure: Body weight
timeFrame: from the completion of treatment to 12 months
measure: Body weight
timeFrame: from the completion of treatment to 15 months
measure: Body weight
timeFrame: from the completion of treatment to 18 months
measure: Body weight
timeFrame: from the completion of treatment to 21 months
measure: Body weight
timeFrame: from the completion of treatment to 24 months
measure: Body weight
timeFrame: from the completion of treatment to 27 months
measure: Body weight
timeFrame: from the completion of treatment to 30 months
measure: Body weight
timeFrame: from the completion of treatment to 33 months
measure: Body weight
timeFrame: from the completion of treatment to 36 months
measure: Tanner stage
timeFrame: from the completion of treatment to 3 months
measure: Tanner stage
timeFrame: from the completion of treatment to 6 months
measure: Tanner stage
timeFrame: from the completion of treatment to 9 months
measure: Tanner stage
timeFrame: from the completion of treatment to 12 months
measure: Tanner stage
timeFrame: from the completion of treatment to 15 months
measure: Tanner stage
timeFrame: from the completion of treatment to 18 months
measure: Tanner stage
timeFrame: from the completion of treatment to 21 months
measure: Tanner stage
timeFrame: from the completion of treatment to 24 months
measure: Tanner stage
timeFrame: from the completion of treatment to 27 months
measure: Tanner stage
timeFrame: from the completion of treatment to 30 months
measure: Tanner stage
timeFrame: from the completion of treatment to 33 months
measure: Tanner stage
timeFrame: from the completion of treatment to 36 months
measure: Occurrence of graft versus host disease
timeFrame: from the completion of treatment to 3 months
measure: Occurrence of graft versus host disease
timeFrame: from the completion of treatment to 6 months
measure: Occurrence of graft versus host disease
timeFrame: from the completion of treatment to 9 months
measure: Occurrence of graft versus host disease
timeFrame: from the completion of treatment to 12 months
measure: Occurrence of graft versus host disease
timeFrame: from the completion of treatment to 15 months
measure: Occurrence of graft versus host disease
timeFrame: from the completion of treatment to 18 months
measure: Occurrence of graft versus host disease
timeFrame: from the completion of treatment to 21 months
measure: Occurrence of graft versus host disease
timeFrame: from the completion of treatment to 24 months
measure: Occurrence of graft versus host disease
timeFrame: from the completion of treatment to 27 months
measure: Occurrence of graft versus host disease
timeFrame: from the completion of treatment to 30 months
measure: Occurrence of graft versus host disease
timeFrame: from the completion of treatment to 33 months
measure: Occurrence of graft versus host disease
timeFrame: from the completion of treatment to 36 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
state: Shanghai
Study officials:
affiliation: Children's Hospital of Fudan University
name: Luo Feihong
role: STUDY_CHAIR
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