Cellular Therapy for Type 1 Diabetes Using Mesenchymal Stem Cells

Sponsor

Medical University of South Carolina (Other)

Overall Status

Recruiting

CT.gov ID

NCT04061746

Collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

Enrollment

Location

Arms

73.5

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this study is to determine the safety and efficacy of fresh metabolically active allogeneic umbilical cord-derived mesenchymal stromal cells (UC-MSCs) for the treatment of new-onset type 1 diabetes (T1D) and to understand the mechanisms of protection. If proven effective, such a strategy can be used as a therapeutic option for T1D patients and potentially other autoimmune disorders.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Biological: Mesenchymal Stem Cells (MSCs) Other: Placebo Infusion (Plasmalyte A with 0.5% human serum albumin)	Phase 1

Detailed Description

This study seeks to find and enroll participants with new onset Type 1 diabetes (T1D) within 6 months of the first dose of insulin. T1D is an autoimmune disease in which T cells attack and destroy insulin-secreting pancreatic β cells leading to insulin deficiency and hyperglycemia in patients. Life-long insulin therapy is the major treatment option. However, insulin therapy is not a cure and a safer and more effective therapy is needed.

Mesenchymal Stromal Cells (MSCs) have emerged as a novel biopharmaceutical approach for many disorders. MSCs are a cellular product that can be derived from a patient's own body (autologous) or from a donor (allogeneic). This study will obtain MSCs from umbilical cords at the time of delivery from normal women who have been extensively screened for infectious diseases. These cells produced at the MUSC Center for Cellular therapy will be used within 3 passages after collection.

Evidence from animal models and clinical trials suggests that MSC infusion suppresses autoimmune and inflammatory diseases such as T1D. One clear message from these trials is that MSCs are effective at suppressing autoimmunity and seem generally safe. This study will measure safety and efficacy of MSCs over the course of 1 year.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Cellular Therapy for Type 1 Diabetes Using Mesenchymal Stem Cells

Actual Study Start Date :

Feb 13, 2020

Anticipated Primary Completion Date :

Mar 31, 2025

Anticipated Study Completion Date :

Mar 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A Treatment 2.5 x 10^6 MSC per kg will be infused intravenously on Day 1	Biological: Mesenchymal Stem Cells (MSCs) Patients in Group A will receive a single MSCs infusion
Placebo Comparator: Group B Placebo Plasmalyte with 0.5% Human Serum Albumin will be infused intravenously on Day 1	Other: Placebo Infusion (Plasmalyte A with 0.5% human serum albumin) Patients in Group B will receive a single infusion of placebo (Plasmalyte A with 0.5% human serum albumin)

Arm

Intervention/Treatment

Experimental: Group A Treatment

2.5 x 10^6 MSC per kg will be infused intravenously on Day 1

Biological: Mesenchymal Stem Cells (MSCs)

Patients in Group A will receive a single MSCs infusion

Placebo Comparator: Group B Placebo

Plasmalyte with 0.5% Human Serum Albumin will be infused intravenously on Day 1

Other: Placebo Infusion (Plasmalyte A with 0.5% human serum albumin)

Patients in Group B will receive a single infusion of placebo (Plasmalyte A with 0.5% human serum albumin)

Outcome Measures

Primary Outcome Measures

12 month Change in C-peptide area under the curve after a 2-hour MMTT [1 year (plus or minus 30 days) after infusion]
Change in beta cell function

Secondary Outcome Measures

6 Month Change in C-Peptide area under the curve after a 2-hour MMTT [6 months (plus or minus 14 days) after infusion]
Change in beta cell function
6 Month peak C-peptide after a 2-hour MMTT [6 months (plus or minus 14 days) after infusion]
Change in beta cell function
1 year peak C-peptide after a 2-hour MMTT [1 year (plus or minus 30 days) after infusion]
Change in beta cell function
Change in 24-hour insulin dose per kilogram between baseline and 1 year measurements [1 year (plus or minus 30 days) after infusion]
Change in beta cell function

Other Outcome Measures

Fasting and postprandial blood glucose levels after MSC infusion [0 - 72 Hours]
Change in beta cell function
Changes in basal C-peptide and hemoglobin A1c [Over the course of 1 year (0, 1, 3, 6, 12 months)]
Change in beta cell function
Change in serum glucagon levels [Over the course of 1 year (0, 1, 3, 6, 12 months)]
Change in alpha cell function
Insulin secretion rate [Over the course of 1 year (0, 1, 3, 6, 12 months)]
Change in beta cell function
Changes in islet autoanitbodies [Over the course of 1 year (0, 1, 3, 6, 12 months)]
Change in autoantibody presence or titer
Change in beta cell death measurements [Over the course of 1 year (0, 1, 3, 6, 12 months)]
Determination of the mechanism of action
Change in blood T-reg number and function [Over the course of 1 year (0, 1, 3, 6, 12 months)]
Determination of the mechanism of action
Change in autoantigen specific T-cell response [Over the course of 1 year (0, 1, 3, 6, 12 months)]
Determination of the mechanism of action
Change in blood autoreactive B cell number, B cell survival, and function [Over the course of 1 year (0, 1, 3, 6, 12 months)]
Determination of the mechanism of action
Changes in mRNA expression in peripheral blood mononuclear cells after treatment [Over the course of 1 year (0, 1, 3, 6, 12 months)]
Determination of the mechanism of action
Changes in serum cytokine levels after treatment [Over the course of 1 year (0, 1, 3, 6, 12 months)]
Determination of the mechanism of action

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 30 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

A new diagnosis of T1D based on the ADA criteria within 6 months of randomization.
Male and female between the ages of 18 and 30
Mentally stable and able to comply with the procedures of the study protocol
Positivity for at least one T1D-associated autoantibody, such as GAD, IA-2 or ZnT8 autoantibodies
At screening, patients must have residual β cell function with a stimulated peak C-peptide >0.2 nmol/l during a 2 hour MMTT
Must be willing to comply with "intensive diabetes management" (* See diabetes management at MUSC below) as directed by the participant's clinician with the goal of maintaining blood glucose as close to normal as possible
Subject must be willing to comply with the schedule of study visits and protocol requirements
Subject with normal laboratory values of: White blood cell counts: between 4,500 to 11,000 per microliter; Platelet counts: 140,000 to 450,000 platelets per microliter of blood; Serum creatinine range is 0.6-1.3 mg/dL, Hepatic function: ALT 5 to 55 units per liter (U/L), AST 5 to 48 U/L.

Exclusion criteria:

Evidence of retinopathy at baseline based on ophthalmologic examination or medical record review.
Body Mass Index < 14 or >35
Presence of malignancy
Subject has abnormally high lipid levels that exceeds > 3 times the upper limit of normal for LDL cholesterol or triglycerides
Subject has blood pressure greater than 160 mmHg systolic or 100 mmHg diastolic at time of consent
Subject is being treated for severe active infection of any type
A female subject who is breast-feeding, pregnant, or intends to become pregnant during the study.
Subject with clinically relevant uncontrolled medical condition not associated with diabetes (e.g. severe psychiatric, hematologic, renal, hepatic, neurologic, cardiac, or respiratory disorder)
Subjects with HgbA1c >12%, and/or fasting blood glucose >270 mg/dL and/or frequent episodes of hypoglycemia (>2 episodes per week of blood glucose levels <60 mg/dL).