Rituximab in New Onset Type 1 Diabetes
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Anti-CD20 (rituximab); Placebo Comparator
Intervention description: Placebo intravenous infusion
Intervention MeSH terms: Rituximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 87.0
Sex: All
Minimum age: 8 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: Newly diagnosed type 1 diabetes; New Onset type 1 diabetes; Preservation of insulin secretion; Type 1 diabetes; Juvenile Onset Diabetes; Insulin Dependent Diabetes; T1D

Summary:

      Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks the
      insulin-producing beta cells in the pancreas. Without these beta cells, the body cannot
      maintain proper blood glucose levels in response to daily activities such as eating or
      exercise. With fewer insulin producing cells blood glucose increases, causing hunger, thirst,
      and unexplained weight loss. By the time these symptoms develop, 80-90% of a person's beta
      cells have already been destroyed. However, this also means that between 10-20% of these
      cells remain that continue to produce insulin.

      Scientists have learned that two types of immune cells, B cells and T cells, are involved in
      causing type 1 diabetes. T cells are responsible for attacking and destroying the beta cells
      that make insulin. Although they don't attack insulin producing cells, B cells may be what
      trigger the T cells to attack.

      This study will investigate the use of rituximab to see if it can help lower the number of
      immune B cells thereby preventing the destruction of any remaining insulin producing beta
      cells that remain at diagnosis. Rituximab is approved by the Food and Drug Administration
      (FDA) for the treatment of a condition called B-lymphocyte lymphoma. Its effects on the
      immune system are well understood through its use in organ transplantation. Research has
      shown that rituximab might be helpful in treating other conditions caused by T cells and B
      cells, including type 1 diabetes. The goal of this study is to find out if rituximab can
      preserve residual insulin secretion and prevent further beta cell destruction in type 1
      diabetes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Between the ages of 8 and 45 years

          -  Within 3 months of diagnosis of type 1 diabetes

          -  Have presence of at least one diabetes-related autoantibody

          -  Must have stimulated C-peptide levels of at least 0.2 pmol/ml measured during a mixed
             meal tolerance test (MMTT) within one month of randomization

          -  If female with reproductive potential, willing to avoid pregnancy and undergo
             pregnancy testing while participating in the study

          -  Have not received an immunization for at least one month

          -  Must be willing to comply with intensive diabetes management

          -  Must weigh at least 25 kg at study entry

        Exclusion Criteria:

          -  Are immunodeficient or have clinically significant chronic lymphopenia

          -  Have an active infection or positive purified protein derivative (PPD) test result

          -  Currently pregnant or lactating; or anticipate becoming pregnant.

          -  Require chronic use of steroids

          -  Have current or past HIV, hepatitis B, or hepatitis C infection

          -  Have any complicating medical issues that interfere with study conduct or cause
             increased risk

          -  Have a history of malignancies

          -  Currently using non-insulin pharmaceuticals that effect glycemic control

          -  Currently participating in another type 1 diabetes treatment study