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

Phase I/II Clinical Trial to Examine the Safety and Efficacy of Transplantation of Mesenchymal Stem Cells in New-onset Type 1 Diabetes Patients

Sponsors

Lead Sponsor: Royan Institute

Collaborator: Tehran University of Medical Sciences
Iranian Stem Cell Council

Source 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.

Overall Status Active, not recruiting
Start Date July 6, 2015
Completion Date April 1, 2020
Primary Completion Date September 26, 2019
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 12 months after the first infusion
Change from baseline number of hypoglycemic Unawareness episodes at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells 12 months after the first infusion
Secondary Outcome
Measure Time Frame
Change from Baseline Fasting Blood Sugar (FBS) at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells 12 months after the first infusion
Change from Baseline C-peptide at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells 12 months after the first infusion
Change from Baseline HbA1C at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells 12 months after the first infusion
Change from Baseline 2-hour postprandial blood glucose at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells 12 months after the first infusion
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 12 months after the first infusion
Change from baseline Lability Index (LI) at 12 Months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells 12 months after the first infusion
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 12 months after the first infusion
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 12 months after the first infusion
Changes from baseline Autoantibodies levels in patients' blood at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells 12 months after the first infusion
Changes from baseline serum cytokines levels in patients' blood at 12 months after intravenous transplantation of autologous bone marrow derived Mesenchymal Stem Cells 12 months after the first infusion
Enrollment 20
Condition
Intervention

Intervention Type: Biological

Intervention Name: Intravenous Injection of autologous mesenchymal stem cells

Description: Intravenous injection 1 millions of bone-marrow derived autologous Mesenchymal Stem Cells (MSCs) per kg of patient's body weight in each dose, weeks 0 & 3

Arm Group Label: Mesenchymal Stem Cells Transplantation

Intervention Type: Other

Intervention Name: Intravenous injection of placebo

Description: Intravenous injection of normal saline (sodium chloride 0.9%)

Arm Group Label: Placebo

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

Gender: All

Minimum Age: 8 Years

Maximum Age: 40 Years

Healthy Volunteers: No

Overall Official
Location
Facility: Royan Institute
Location Countries

Iran, Islamic Republic of

Verification Date

September 2019

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Mesenchymal Stem Cells Transplantation

Type: Experimental

Description: The patients with Type 1 Diabetes, who will receive Intravenous injection of autologous bone-marrow derived mesenchymal stem cells

Label: Placebo

Type: Placebo Comparator

Description: The patients with Type 1 Diabetes, who will receive intravenous injection of normal saline (sodium chloride 0.9%)

Acronym MSCTXT1DM
Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Crossover Assignment

Primary Purpose: Treatment

Masking: Triple (Participant, Care Provider, Outcomes Assessor)

Source: ClinicalTrials.gov