New Onset of Type 1 Diabetes Mycophenolate Mofetil-Daclizumab Clinical Trial
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Mycophenolate mofeteil (MMF); Daclizumab (DZB); Placebo control for Mycophenolate mofeteil (MMF); Placebo control for Daclizumab (DZB)
Intervention description: Placebo pills taken orally; saline intravenous infusions
Intervention MeSH terms: Mycophenolic Acid; Daclizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 126.0
Sex: All
Minimum age: 8 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: immunosuppressive therapy; Type 1 Diabetes TrialNet; TrialNet; POPPII; POPPII-1

Summary:

      The objective of this study is to identify immune intervention strategies that will preserve
      residual beta cell function at the onset of type 1 diabetes. Scientific evidence developed
      over the last 10 - 20 years suggests that type 1 diabetes is a chronic, slowly progressive
      autoimmune disease and that clinical symptoms do not develop until at least 80% - 90% of beta
      cell mass has been destroyed as a result of the autoimmune process. It is now recognized that
      preservation of remaining beta cells is clinically important as the ability to secrete, even
      small amounts of insulin, can make the disease easier to control and help minimize
      complications associated with having years of inadequate glycemic control.

      This clinical trial is the first in a series of studies to be launched by the TrialNet Study
      Group to test various interventions for preserving residual beta cell function in new onset
      type 1 diabetes. Specifically, this study is designed to determine the ability of
      Mycophenolate Mofetil (MMF/CellCept) used alone, or in combination with Daclizumab
      (DZB/Zenapax) to see if it is possible to stop the immune system from destroying beta cells
      in new onset type 1 diabetes patients (within 3 months of diagnosis.)

      Researchers have made great strides in understanding how the immune system works and in
      changing the activity of immune cells with medicines called immunotherapies. Some
      immunotherapies work by making the immune system less active. Scientists have discovered that
      key immune cells, called T cells, help to cause type 1 diabetes. These T cells are largely
      responsible for attacking the beta cells that produce insulin. Doctors have found medicines
      that slow or suppress the activity of T cells. It is hoped that these immunosuppressive
      medicines can help treat type 1 diabetes by stopping T cells before they destroy all of the
      beta cells.

      Medicines that make the immune system less active have been developed and studied for other
      diseases. Mycophenolate mofetil (MMF) and Daclizumab (DZB) are two of these medicines. Their
      effects on the immune system are well understood. Researchers believe these medicines may
      lessen the immune system's destruction of beta cells that leads to type 1 diabetes. In
      addition, researchers hope the effect of these medicines will last longer than other
      therapies.

      The goal of this study is to find out if two medicines are able to stop the ongoing
      destruction of beta cells which are still functioning at the time type 1 diabetes is
      diagnosed. The two immunosuppressive medications being tested are Mycophenolate mofetil
      (MMF/CellCept®) and Daclizumab (DZB/Zenapax®). They work by making the immune system less
      active. TrialNet researchers hope that these medications will help maintain insulin secretion
      from remaining beta cells and thus help to maintain better glycemic control. Even if the
      medications work, study participants will still need to take insulin injections but it may
      make it easier to control normal blood sugar levels which can help reduce long-term
      complications of diabetes such as blindness, kidney failure, nerve damage, heart attack and
      stroke.

      The aim is to arrest beta cell destruction in newly diabetic subjects because immune
      modulation may not work well alone once the autoimmune process has progressed to complete or
      near complete destruction of beta cells. The study's rationale is to demonstrate a meaningful
      preservation of islet function with minimal immune system side effects over the 4-year course
      of this study.

      The data from this clinical trial could serve as the basis for a larger trial if the results
      are sufficiently positive, or they could suggest other combined intervention trials that
      might achieve either better efficacy or potentially preserve C-peptide without the need for
      continued immunosuppression.
    

Eligibility criteria:

        Inclusion Criteria:

        Potential participants must meet the following inclusion criteria:

          -  Be within 3-months of diagnosis of type 1 diabetes based on American Diabetes
             Association (ADA) criteria

          -  Be between the ages of 8 and 45 years old

          -  Must have stimulated C-peptide levels > 0.2 pmol/ml (measured during an MMTT
             administered no more than one month prior to the date of randomization)

          -  Must have either detectable anti-GAD, anti-ICA512/IA-2, insulin autoantibodies (unless
             received insulin therapy for 7 days or more), or islet cell autoantibodies.

        [The reason for inclusion of these enrollment criteria is to avoid inclusion of patients
        with "Type 1B diabetes mellitus", which may not involve the immunologic criteria measured
        by the assays that will be utilized.]

          -  If participant has reproductive potential, he or she must be agreeable to an effective
             form of birth control (unless abstinence is the chosen method).

          -  If participant is female with reproductive potential, she must be willing to undergo
             pregnancy testing and to report possible or confirmed pregnancies promptly during the
             course of the MMF/DZB study.

          -  Must be willing to comply with intensive diabetes management. The goal of management
             will be an HbA1c of 7.0% for all participants, regardless of age. Participants will be
             expected to take a sufficient number of daily insulin shots to meet this goal.
             Alternatively, participants can use insulin pump therapy. Participants will also be
             expected to test their blood sugar at least 3-4 times per day. There will be a
             Certified Diabetes Educator working with study participants to achieve these goals.

        Exclusion Criteria:

        Potential participants must not meet any of the following exclusion criteria:

          -  Have any complicating medical issues that would interfere with blood drawing or
             monitoring.

          -  Have a Body Mass Index (BMI) that is greater than the 95th percentile for age and
             gender.

          -  Have serologic evidence of HIV infection.

          -  Have serologic evidence of Hepatitis B infection.

          -  Have serologic evidence of Hepatitis C infection.

          -  Have abnormal liver function tests.

          -  Have a history of leukopenia and/or neutropenia.

          -  Have a history of chronic peptic ulcer disease, erosive esophagitis, chronic
             inflammatory bowel disease and/or chronic colonic disease.

          -  Have a positive PPD test result.

          -  Have had any live vaccinations in the preceding 6 weeks (e.g. MMR-second dose, live
             flu vaccine, varicella vaccine, live polio vaccine, yellow fever vaccine).

          -  Resides outside reasonable geographical proximity to the clinic (i.e., residence
             outside the state in which the Investigator and study reside, residence outside an
             immediately neighboring state, or residence outside an area that the Investigator
             considers reasonable). It is left to the Investigator's discretion to decide if a
             patient's geographical residence is prohibitive to complete study participation.

          -  Require chronic use of steroids or other immunosuppressive agents for other
             conditions.

          -  Be currently pregnant or 3 months postpartum.

          -  Be currently nursing or within 6 weeks of having completed nursing.

          -  Anticipate getting pregnant, or fathering a child, during the study.