Primary Outcome Measures:
- Number of Participants with Adverse events as a Measure of Safety and Tolerability. [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
Primary outcome measures will be the number of participants with adverse events, laboratory abnormalities and other signs of toxicity. Particular focus will be on the number and severity of infusion reactions, complications related to infection, and any potential negative impact on the course of diabetes.
Secondary Outcome Measures:
- C-peptide response [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Secondary diabetes-related outcome measure will include C-peptide response during mixed meal tolerance tests at 26 and 52 weeks
- Insulin Use [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Secondary diabetes-related outcome measure will include insulin use
- Hemoglobin A1c [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Secondary diabetes-related outcome measure will include hemoglobin A1c
- Immunologic Markers [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Secondary surrogate immunologic markers will include those related to general immune function and those related to the diabetes autoimmune response.
Intervention Details:
Biological: Ex vivo Expanded Human Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells
Patients with Type 1 Diabetes Mellitus will have their regulatory T cells (Tregs) isolated by researchers. The researchers will multiply/expand the Tregs in the laboratory using anti-CD3/anti-CD28 coated beads plus IL-2. Then, the Tregs will be infused back into the patient in a single infusion. The first cohort will receive 0.05 x10^8 cells. The second cohort will receive 0.4 x10^8 cells. The third cohort will receive 3.2 x10^8 cells. The fourth cohort will receive 26 x10^8 cells.
Currently, there is no approved medical treatment for preservation of the body's ability to produce insulin in patients with Type 1 Diabetes Mellitus (T1DM), and the progression of the disease can have devastating consequences. Inadequate blood glucose control results in many long term complications including kidney disease, blindness, amputation and nerve damage. In spite of the advances in insulin therapy and subsequent glucose control, patients are required to infuse insulin subcutaneously daily throughout their lives, monitor their diet and blood sugar levels, and deal with life-long uncertainties. The investigational therapy under study in this trial, regulatory T cells (Tregs), offers the hope of stabilizing diabetes. Tregs are a specialized subset of T cells that function to control the immune response. Pre-clinical studies in non-obese diabetic mice have demonstrated that adoptive transfer of Tregs can slow diabetes progression and, in some cases, reverse new onset diabetes. The primary objective of this study is to assess the safety of a single intravenous infusion of Tregs in patients with T1DM. The study will also assess the effect of Tregs on insulin-producing beta cell function as well as other outcomes related to diabetes management. Researchers will isolate Tregs from the patient's own blood using specific T cell surface markers (CD4, CD25, and CD127). This subset of cells is then expanded in the laboratory by co-stimulating with anti-CD3 and anti-CD28 immobilized on magnetic beads, and with the use of growth medium containing human serum and IL-2. Following the 14-day expansion, anti-CD3/anti-CD28 beads will be removed and the Tregs will be concentrated and consolidated. The cells will then be resuspended in sterile infusion solution at the required concentration and infused back into the patient through a standard peripheral intravenous line. Subjects will be observed overnight in the clinical research center for any possible side effects following the infusion. A total of 14 subjects will be enrolled. The study will involve 4 dosing cohorts with 3 or 4 adults in each cohort. Each cohort will receive increasing amounts of Tregs. Subjects will be followed over five years to assess safety of the Treg therapy.
Purpose
