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Mesenchymal Stem Cells Transplantation in Newly Diagnosed Type-1 Diabetes Patients

Phase 1
Conditions
Diabetes Mellitus, Insulin-Dependent
Diabetes Mellitus
Diabetes Mellitus, Type 1
Interventions
Biological: Intravenous Injection of autologous mesenchymal stem cells
Other: Intravenous injection of placebo
Registration Number
NCT04078308
Lead Sponsor
Royan Institute
Brief Summary

Study Objects: Diabetes is an autoimmune disease which is mainly caused an immune reaction to beta cells in the pancreas. In this study, mesenchymal stem cells will be used for immune response modulation and improving regeneration. Study design and method: In a Triple blinded randomized placebo-controlled phase I/II clinical trial, 20 patients with newly diagnosed type-1 diabetes who would be visited in Children's Growth and Development Research Center of Tehran University of Medical Sciences and Royan Institute Cell Therapy Center, would be assessed through two groups including the case group and the placebo group. Participants: Patients of both sexes in a range of 8 to 40 years old who have been diagnosed to have type-1 diabetes in no more than 6 weeks, antibody against beta cells diagnosed in their blood, fasting c-peptide more than or equal to 0.3 ng/ml, and are not suffered from other acute or chronic diseases and cancers, would be studied. Interventions: Intravascular transplantation of autologous mesenchymal stem cells in the case group; placebo injection in the control group. Outcome variables: safety and efficacy.

Detailed Description

Diabetes is an autoimmune disease which is mainly caused by an immune reaction to beta cells in the pancreas. Today, insulin injection is a routine treatment for diabetes. Although injected insulin maintains blood glucose, this method cannot result in physiologic reaction to blood glucose changes. Moreover, patients are encountered with diabetes complications like neuropathy, nephropathy, visual and cardiovascular problems, and hypoglycemic unawareness. Therefore, based on previous studies, a treatment option that leads to pancreatic beta cell restoration and inhibits the immune response to these cells could be a hopeful clinical choice. In this clinical trial, autologous bone marrow-derived mesenchymal stem cells will be used for immune response modulation and improving regeneration. Hence, based on inclusion and exclusion criteria, 20 patients with type-1 diabetes will be selected and after clarifying the procedure and fulfilling the agreement to participate in this trial, they will be sorted in two groups. Bone marrow is aspirated from patients bone and after isolation of Mesenchymal stem cells and characterization of these cells, patients in case group will be intravenously injected by 1 million autologous mesenchymal stem cells per kg of patient's body weight in each dose in week 0 and 3, whereas the control group receives a placebo. Then patients will be followed up for 1 year. During this time, different parameters would be evaluated in weeks 1, 2,4, and Months 2,3,6,9 and 12. Laboratory screenings will be done during this period to evaluate the safety and efficacy of this treatment.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
20
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Mesenchymal Stem Cells TransplantationIntravenous Injection of autologous mesenchymal stem cellsThe patients with Type 1 Diabetes, who will receive Intravenous injection of autologous bone-marrow derived mesenchymal stem cells
PlaceboIntravenous injection of placeboThe patients with Type 1 Diabetes, who will receive intravenous injection of normal saline (sodium chloride 0.9%)
Primary Outcome Measures
NameTimeMethod
Change from baseline number of hypoglycemic Unawareness episodes at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells12 months after the first infusion

Number of hypoglycemic unawareness episodes will be assessed by evaluating patients' blood glucose monitoring sheets

Number of participants with treatment-related adverse events as assessed by CTCAE v5.012 months after the first infusion

Safety will be assessed by evaluating patients based on CTCAE (v.5) to assess treatment-related adverse events after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells

Secondary Outcome Measures
NameTimeMethod
Change from Baseline HbA1C at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells12 months after the first infusion

Assessing HbA1C at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells and compare the results with baseline HbA1C

Change from Baseline 2-hour postprandial blood glucose at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells12 months after the first infusion

Assessing 2-hour postprandial blood glucose at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells and compare the results with baseline 2-hour postprandial blood glucose

Change from Baseline SF-36 Quality of life (QOL) questionnaire score at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells12 months after the first infusion

Assessing change in patients' Quality of life by answering SF-36 questionnaire before transplantation and 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells; This questionnaire asks about general aspects of patients' life.

The results would be reported as the total score and the scale range is from 0% to 100%. 0% is considered as worse condition and 100% is considered as the best condition.

Change from Baseline C-peptide at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells12 months after the first infusion

Assessing serum C-peptide at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells and compare the results with baseline serum C-peptide level

Change from Baseline Fasting Blood Sugar (FBS) at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells12 months after the first infusion

Assessing Fasting Blood Sugar (FBS) at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells and compare the results with baseline Fasting Blood Sugar (FBS)

Change from Baseline daily dose of exogenous insulin injected by patients (IU/kg/day) at 12 Months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells12 months after the first infusion

Exogenous Insulin requirement of patients will be measured based on their daily insulin injection report sheets, total injected insulin units per day will be divided by patient's weight in order to be comparable between different patients.

Changes from baseline Autoantibodies levels in patients' blood at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells12 months after the first infusion

Assessing patients Islet Cell Antibodies (ICA), Glutamic Acid Decarboxylase Antibodies (GADA), Insulinoma-Associated protein-2 Antibodies (IA-2A) levels after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells

Changes from baseline serum cytokines levels in patients' blood at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells12 months after the first infusion

Assessing serum cytokines levels of patients after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells

Change from baseline Lability Index (LI) at 12 Months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells12 months after the first infusion

Assessing 2 weeks of blood glucose report sheets, calculation is based on the changes in blood glucose levels over time

Change from Baseline Diabetes Specific Quality of life (DQOL) questionnaire score at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells12 months after the first infusion

Assessing change in patients' Quality of life by answering Diabetes Specific Quality of Life (DQOL) questionnaire before transplantation and 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells; This questionnaire asks about different aspects of patients' life in relation to diabetes.

The results would be reported as the total score and the scale range is from 0% to 100%. 0% is considered as worse condition and 100% is considered as the best condition.

Trial Locations

Locations (1)

Royan Institute

🇮🇷

Tehran, Iran, Islamic Republic of

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