T1DM Immunotherapy Using CD4+CD127lo/-CD25+ Polyclonal Tregs
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 1

Summary: 
      The investigational therapy under study in this trial, regulatory T cells (Tregs), offers the
      hope of stabilizing further destruction of insulin producing beta cells in type 1 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 purpose of this Phase 1 study is to assess the safety and feasibility of intravenous
      infusion of ex vivo selected and expanded autologous polyclonal Tregs in patients with type 1
      diabetes (T1DM) to support dose selection for a future efficacy trial. The study also aims to
      assess the effect of Tregs on beta cell function as well as on other measures of diabetes
      severity and the autoimmune response underlying T1DM.
    

Detailed description: 
      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.
    

Intervention name(s): Ex vivo Expanded Human Autologous Polyclonal Regulatory T Cells
Intervention type(s): Biological
Intervention description(s): 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.
Other intervention name(s): Tregs
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Diabetes; Treg