Diabetes Prevention - Immune Tolerance
Condition: Prediabetes; Type 1 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 2

Summary: 
      A double-blind, randomized investigator-initiated study to determine the safety and the
      effect of Diamyd® on the progression to type 1 diabetes in children with multiple islet cell
      autoantibodies

      Eligible children are 4 years or older, have positive GAD-antibodies and at least one
      additional autoantibody and not yet diabetes.

      Objectives:

      DiAPREV-IT is the first prevention study with Diamyd®, where the drug is given before onset
      of type 1 diabetes.

      The primary objective is to demonstrate that Diamyd® is safe in children at risk for type 1
      diabetes.

      The secondary objective is to evaluate if Diamyd® may delay or stop the autoimmune process
      leading to clinical type 1 diabetes in children with ongoing persistent beta-cell
      autoimmunity as indicated by multiple positive islet cell autoantibodies.
    

Detailed description: 
      A double-blind, randomized investigator-initiated study to determine the safety and the
      effect of Diamyd® on the progression to type 1 diabetes in children with multiple islet cell
      autoantibodies

      Eligible children are 4 years or older, have positive GAD-antibodies and at least one
      additional autoantibody and not yet diabetes.

      Objectives:

      DiAPREV-IT is the first prevention study with Diamyd®, where the drug is given before onset
      of type 1 diabetes.

      The primary objective is to demonstrate that Diamyd® is safe in children at risk for type 1
      diabetes.

      The secondary objective is to evaluate if Diamyd® may delay or stop the autoimmune process
      leading to clinical type 1 diabetes in children with ongoing persistent beta-cell
      autoimmunity as indicated by multiple positive islet cell autoantibodies.

      Procedure:

      50 children will be randomized to 2 injections of Diamyd® or placebo. In DIAPREV-IT we will
      use the previously tested dose of 20 µg Diamyd® administered as a prime-and-boost at days 1
      and 30, as no serious adverse reactions have been observed with this regimen. The children
      will be followed every 3rd month for 5 years. Before the first injection of study drug both
      intravenous (IvGTT) and oral (OGTT) glucose tolerance test will be performed. These will be
      repeated during the study with OGTT every 6 month visit and IvGTT every full year visit.

      Safety variables:

      Collection of adverse events, serious adverser events, hematology, chemistry, titles of
      autoantibodies.

      Effect variables:

      The cumulative incidence of diabetes onset over time since randomization within each
      treatment group will be estimated using the Kaplan-Meier method (proportion surviving
      diabetes-free as a function of time).

      Secondary efficacy variables:

      Change in first-phase insulin response and K-value on IvGTT from baseline Change in fasting,
      120 minutes and AUC C-peptide levels on OGTT Change in fasting, 120 minutes and AUC glucose
      on OGTT Change in HbA1c from baseline All measures during 5 years follow-up.

      Children developing diabetes in the study will be offered to participate in a postdiagnosis
      protocol. Children who have had two doses of active Diamyd in the main study will be given
      one additional dose of 20 microgram Diamyd followed by one dose of placebo after 30 days.
      Children who have had two doses of placebo will be given two doses of 20 microgram Diamyd
      with 30 days in between. Post diagnosis follow up will proceed for at least 15 months from
      the first post diagnosis injection with collection of adverse events and metabolic evaluation
      with Mixed meal tolerance tests.
    

Intervention name(s): Placebo comparator; Diamyd
Intervention type(s): Other; Drug
Intervention description(s): Placebo comparator day 1 and 30 in non-diabetic children with multiple islet autoantibodies.
Post diagnosis: Two doses of 20 microgram Diamyd day 1 and 30 in children originally receiving placebo.; 20 microgram day 1 and 30 in non-diabetic children with multiple islet autoantibodies.
Post diagnosis: Two doses of Diamyd followed to children originally receiving Diamyd
Other intervention name(s): Alum-GAD
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: Alum-GAD; Type 1 diabetes; prevention; immune tolerance; glucose tolerance; glutamate decarboxylase autoantibodies