Clinical trial NCT04078308: Mesenchymal Stem Cells Transplantation in Newly Diagnosed Type-1 Diabetes Patients
Official title: Phase I/II Clinical Trial to Examine the Safety and Efficacy of Transplantation of Mesenchymal Stem Cells in New-onset Type 1 Diabetes Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Diabetes Mellitus
Diabetes Mellitus, Type 1
Diabetes Mellitus, Insulin-Dependent
Keywords: Diabetes Mellitus
Diabetes Mellitus, Type 1
Cell Transplantation
Autologous Transplantation
Mesenchymal Stem Cell
Lead sponsor: Royan Institute
Sponsor class: OTHER_GOV
Collaborators: name: Tehran University of Medical Sciences
name: Iranian Stem Cell Council
First posted: 2019-09-06
Enrollment: 20
Sex: ALL
Minimum age (years): 8
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria:

* Type 1 diabetes detection in less than 6 weeks
* Diabetes diagnosis according to American Diabetes Association (ADA)
* Presence of Antibodies against pancreatic beta cells
* Fasting C-peptide ≥ 0.3 ng/ml

Exclusion Criteria

* Pregnancy or breastfeeding
* Cancer
* Any acute or severe disease (According to physicians' diagnosis: such as cardiac, pulmonary, hepatic, kidney, mental, ... diseases)
* Positive results for: Human Immunodeficiency Virus (HIV), Human T-Lymphotropic Virus (HTLV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Cytomegalovirus (CMV)
* Immune deficient or hyper aesthesia
* History of severe ketoacidosis

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: 12 months after the first infusion
measure: Change from baseline number of hypoglycemic Unawareness episodes at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells
timeFrame: 12 months after the first infusion
Secondary outcomes:
measure: Change from Baseline Fasting Blood Sugar (FBS) at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells
timeFrame: 12 months after the first infusion
measure: Change from Baseline C-peptide at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells
timeFrame: 12 months after the first infusion
measure: Change from Baseline HbA1C at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells
timeFrame: 12 months after the first infusion
measure: Change from Baseline 2-hour postprandial blood glucose at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells
timeFrame: 12 months after the first infusion
measure: 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 Cells
timeFrame: 12 months after the first infusion
measure: Change from baseline Lability Index (LI) at 12 Months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells
timeFrame: 12 months after the first infusion
measure: Change from Baseline SF-36 Quality of life (QOL) questionnaire score at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells
timeFrame: 12 months after the first infusion
measure: Change from Baseline Diabetes Specific Quality of life (DQOL) questionnaire score at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells
timeFrame: 12 months after the first infusion
measure: Changes from baseline Autoantibodies levels in patients' blood at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells
timeFrame: 12 months after the first infusion
measure: Changes from baseline serum cytokines levels in patients' blood at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells
timeFrame: 12 months after the first infusion
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Royan Institute
Study officials:
affiliation: Royan Institute, ACECR, Tehran, I.R. Iran
name: Abdolhossein Shahverdi, PhD
role: STUDY_CHAIR
affiliation: Department of Stem Cells Biology and Technology, Cell Science Research Center, Royan Institute for Stem Cells Biology & Technology, ACECR, Tehran, I.R. Iran
name: Hossein Baharvand, PhD
role: STUDY_DIRECTOR
affiliation: Tehran University of Medical Sciences, Tehran, I.R. Iran
name: Ali Rabbani, MD
role: STUDY_DIRECTOR
affiliation: Department of Stem Cells Biology and Technology, Cell Science Research Center, Royan Institute for Stem Cells Biology & Technology, ACECR, Tehran, I.R. Iran
name: Ensiyeh Hajizadeh saffar, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Izadi M, Sadr Hashemi Nejad A, Moazenchi M, Masoumi S, Rabbani A, Kompani F, Hedayati Asl AA, Abbasi Kakroodi F, Jaroughi N, Mohseni Meybodi MA, Setoodeh A, Abbasi F, Hosseini SE, Moeini Nia F, Salman Yazdi R, Navabi R, Hajizadeh-Saffar E, Baharvand H. Mesenchymal stem cell transplantation in newly diagnosed type-1 diabetes patients: a phase I/II randomized placebo-controlled clinical trial. Stem Cell Res Ther. 2022 Jun 20;13(1):264. doi: 10.1186/s13287-022-02941-w.