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

Overview

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.

Interventions

• 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 t

Primary outcome measures

• Concentration of serum C-peptide [Time frame: from the completion of treatment to 3 months]
• Concentration of serum C-peptide [Time frame: from the completion of treatment to 3 years]

Secondary outcome measures (12)

• Concentration of serum C-peptide [Time frame: from the completion of treatment to 6 months]
• Concentration of serum C-peptide [Time frame: from the completion of treatment to 9 months]
• Concentration of serum C-peptide [Time frame: from the completion of treatment to 12 months]
• Concentration of serum C-peptide [Time frame: from the completion of treatment to 15 months]
• Concentration of serum C-peptide [Time frame: from the completion of treatment to 18 months]
• Concentration of serum C-peptide [Time frame: from the completion of treatment to 21 months]
• Concentration of serum C-peptide [Time frame: from the completion of treatment to 24 months]
• Concentration of serum C-peptide [Time frame: from the completion of treatment to 27 months]
• Concentration of serum C-peptide [Time frame: from the completion of treatment to 30 months]
• Concentration of serum C-peptide [Time frame: from the completion of treatment to 33 months]
• Concentration of serum insulin [Time frame: from the completion of treatment to 3 months]
• Concentration of serum insulin [Time frame: from the completion of treatment to 6 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Children's Hospital of Fudan University — Shanghai

Publications

• Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, Malanda B. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018 Apr;138:271-281. doi: 10.1016/j.diabres.2018.02.023. Epub 2018 Feb 26. PMID 29496507
• Fu H, Shen SX, Chen ZW, Wang JJ, Ye TT, LaPorte RE, Tajima N. Shanghai, China, has the lowest confirmed incidence of childhood diabetes in the world. Diabetes Care. 1994 Oct;17(10):1206-8. doi: 10.2337/diacare.17.10.1206. PMID 7821146
• Zhao Z, Sun C, Wang C, Li P, Wang W, Ye J, Gu X, Wang X, Shen S, Zhi D, Lu Z, Ye R, Cheng R, Xi L, Li X, Zheng Z, Zhang M, Luo F. Rapidly rising incidence of childhood type 1 diabetes in Chinese population: epidemiology in Shanghai during 1997-2011. Acta Diabetol. 2014 Dec;51(6):947-53. doi: 10.1007/s00592-014-0590-2. Epub 2014 Apr 29. PMID 24777734
• Daniels M, DuBose SN, Maahs DM, Beck RW, Fox LA, Gubitosi-Klug R, Laffel LM, Miller KM, Speer H, Tamborlane WV, Tansey MJ; T1D Exchange Clinic Network. Factors associated with microalbuminuria in 7,549 children and adolescents with type 1 diabetes in the T1D Exchange clinic registry. Diabetes Care. 2013 Sep;36(9):2639-45. doi: 10.2337/dc12-2192. Epub 2013 Apr 22. PMID 23610082
• Amin R, Widmer B, Prevost AT, Schwarze P, Cooper J, Edge J, Marcovecchio L, Neil A, Dalton RN, Dunger DB. Risk of microalbuminuria and progression to macroalbuminuria in a cohort with childhood onset type 1 diabetes: prospective observational study. BMJ. 2008 Mar 29;336(7646):697-701. doi: 10.1136/bmj.39478.378241.BE. Epub 2008 Mar 18. PMID 18349042
• Mollsten A, Svensson M, Waernbaum I, Berhan Y, Schon S, Nystrom L, Arnqvist HJ, Dahlquist G; Swedish Childhood Diabetes Study Group; Diabetes Incidence Study in Sweden; Swedish Renal Registry. Cumulative risk, age at onset, and sex-specific differences for developing end-stage renal disease in young patients with type 1 diabetes: a nationwide population-based cohort study. Diabetes. 2010 Jul;59(7) PMID 20424230
• American Diabetes Association. (2) Classification and diagnosis of diabetes. Diabetes Care. 2015 Jan;38 Suppl:S8-S16. doi: 10.2337/dc15-S005. No abstract available. PMID 25537714
• Wildin RS, Smyk-Pearson S, Filipovich AH. Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. J Med Genet. 2002 Aug;39(8):537-45. doi: 10.1136/jmg.39.8.537. PMID 12161590

Identifiers

NCT: NCT03835312 · SeqTranUCBC&IC-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗