New Onset of Type 1 Diabetes Mycophenolate Mofetil-Daclizumab Clinical Trial
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      Design of Study:

      The study is a multi-center, three-arm, randomized, double-masked, placebo-controlled
      clinical trial. Comparisons will be made among the three groups, which are:

        -  Mycophenolate mofetil active drug with Daclizumab (DZB) placebo IV

        -  Mycophenolate mofetil active drug with active Daclizumab IV

        -  Mycophenolate mofetil placebo with Daclizumab placebo IV

      Participants that agree to enroll in the study will be asked to take study medications for
      two years. MMF is given by mouth twice a day. DZB is given by an intravenous infusion twice,
      once at the time of enrollment and again two weeks later. Both these medications are approved
      by the U.S. Food and Drug Administration and are used by people who have received an organ
      transplant. This study is testing a new use of these medications to preserve insulin
      secretion by delaying or stopping further destruction of insulin-secreting cells in people
      with newly diagnosed type 1 diabetes. Both MMF and DZB make the immune system less active.
      Participants will be monitored closely for any possible side effects that can occur from
      taking either DZB and/or MMF due to decreased activity of the immune system.

      Participants will need to go to the Clinical Center for visits and tests. For the first month
      participants will come in every week; then participants will come in at month 2 and month 3.
      After the month 3 visit, visits will occur about every three months. At most visits, blood
      will be drawn and participants will meet with a study physician to review their overall
      diabetes management, and be monitored for any possible side-effects from the study
      medication.

      Participants will be asked to do a longer test called a Mixed Meal Tolerance Test (MMTT) at
      the initial visit and at five additional visits while taking the assigned study medication.
      The MMTT involves drinking a special drink which has a controlled amount of carbohydrates,
      protein, and fat to measure residual insulin secretion. The test requires having an IV
      inserted into the arm and having blood samples taken from the IV over a period of 2 to 4
      hours. After completing the two year period of taking the study medication, participants will
      be asked to return every 3-6 months for an additional 1-2 years to evaluate their ability to
      secrete insulin after discontinuing the study medication.
    

Intervention name(s): Mycophenolate mofeteil (MMF); Daclizumab (DZB); Placebo control for Mycophenolate mofeteil (MMF); Placebo control for Daclizumab (DZB)
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Placebo pills taken orally; saline intravenous infusions
Intervention MeSH terms: Mycophenolic Acid; Daclizumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Other
Keywords: immunosuppressive therapy; Type 1 Diabetes TrialNet; TrialNet; POPPII; POPPII-1