Oral Insulin for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Oral Insulin; Placebo
Intervention description: 7.5 mg oral insulin or placebo given before breakfast on a daily basis.; Placebo capsule designed to match active drug
Intervention MeSH terms: Insulin
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 560.0
Sex: All
Minimum age: 3 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: oral insulin; autoantigen; self tolerance; oral tolerance; Diabetes Prevention Trial - 1 (DPT-1); prevention; "at risk" for developing type 1 diabetes; juvenile diabetes; Type 1 diabetes (T1D); diabetes mellitus; Type 1 diabetes TrialNet; TrialNet

Summary:

      Type 1 diabetes (T1D) is an autoimmune disease. This means that the immune system (the part
      of the body which helps fight infections) mistakenly attacks and destroys the cells that
      produce insulin (islet cells found in the pancreas). As these cells are destroyed, the body's
      ability to produce insulin decreases. There is evidence suggesting that repeated oral
      administration of an autoantigen (the same protein that the immune system is reacting to) may
      introduce a protective immunity and cause the immune system to stop its attack. An earlier,
      large scale study was done to see if oral insulin could delay or prevent the development of
      Type 1 diabetes in relatives at risk for developing Type 1 diabetes. The overall results
      showed that for the entire study population, oral insulin did not delay or prevent Type 1
      diabetes. However, an analysis that was done after the conclusion of the trial suggested a
      potential beneficial effect in a subgroup of participants. The participants who seemed to
      benefit from oral insulin had higher levels of insulin autoantibodies which are directed
      against insulin itself ( called mIAA).

      The Type 1 Diabetes TrialNet study group will further explore the potential role of oral
      insulin to delay or prevent Type 1 diabetes in a similar group of people. The study will also
      include a secondary group of individuals at different levels of risk than those in the
      primary cohort to gather information for future studies.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Have a proband with Type 1 diabetes mellitus (T1DM). A proband is an individual
             diagnosed with diabetes before age 40 and started on insulin therapy within 1-year of
             diagnosis. Probands considered to have type 1 diabetes by their physician who do not
             meet this definition will be referred to the TrialNet Eligibility Committee.

          2. If the proband is a parent, sibling or a child, the study participant must be 3 -45
             years of age. If the proband is a second or third degree relative (i.e. niece, nephew,
             aunt, uncle, grandparent, cousin, or half-sibling), the study participant must be 3-20
             years of age.

          3. Willing to sign Informed Consent Form.

          4. Oral glucose tolerance test (OGTT) performed within 7 weeks prior to randomization in
             which:

               -  fasting plasma glucose < 110 mg/dL (6.1 mmol/l), and

               -  2 hour plasma glucose < 140 mg/dL (7.8 mmol/l)

          5. mIAA confirmed positive within the previous six months.

          6. Two samples with at least one autoantibody other than mIAA positive within the
             previous six months.

        Exclusion Criteria:

          1. Does not satisfy the above inclusion criteria. Subjects with mIAA positive but no
             other autoantibodies positive are not eligible for randomization.

          2. Has severe active disease, e.g. chronic active hepatitis, severe cardiac, pulmonary,
             renal, hepatic, immune deficiency and/or disease that is likely to limit life
             expectancy or lead to therapies such as immunosuppression during the time of the
             study.

          3. Prior participation in a trial for prevention of T1DM, e.g. nicotinamide, insulin,
             immunosuppressive drugs.

          4. History of treatment with insulin or oral hypoglycemic agent.

          5. History of therapy with immunosuppressive drugs or glucocorticoids within the past two
             years for a period of more than three months.

          6. Ongoing use of medications known to influence glucose, i.e. sulfonylureas, growth
             hormone, metformin, anticonvulsants, thiazide or potassium depleting diuretics, beta
             adrenergic blockers, niacin. Subjects on such medications should be changed to a
             suitable alternative, if available, and will become eligible one month after
             medication is discontinued.

          7. Pregnant or intends to become pregnant while on study or lactating.

          8. Deemed unlikely or unable to comply with the protocol.

          9. OGTT that reveals Diabetes, Impaired Glucose Tolerance (IGT), or Impaired Fasting
             Glucose (IFG).

             Diabetes is defined by:

               -  fasting plasma glucose ³ 126 mg/dL (7 mmol/l), OR

               -  2 hour plasma glucose ³ 200 mg/dL (11.1 mmol/l)

             IGT is defined by:

               -  fasting plasma glucose < 126 mg/dL (7 mmol/l), and

               -  2 hour plasma glucose 140-199 mg/dL (7.8 - 11mmol/l),

             IFG is defined by:

               -  fasting plasma glucose 110-125 mg/dL (6.1-6.9 mmol/l) AND

               -  2 hour plasma glucose < 140 mg/dL (7.8 mmol/l)

         10. Subject has HLA DQA1*0102, DQB1*0602 haplotype.