Oral Insulin for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus (TN07 Oral Insulin)

General Description

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). Eligible participants will be randomized to receive either oral insulin (7.5 mg of recombinant human insulin crystals) or placebo daily.

All participants randomized into TrialNet 07 were seen at a study site for a follow-up evaluation, three and six months after randomization, and every six months thereafter. Participants will be contacted by phone between 6-monthly clinic visits to assess changes in diabetes status, medication compliance and adverse events. These phone contacts will occur approximately 3 months from the date of the participants previous clinic visit.

At the study visits, participants underwent assessments of their insulin production, immunologic status, and overall health. As the primary outcome measure, subjects will be followed until development of type 1 diabetes or the conclusion of the study. The trial is expected to last approximately 7-8 years or until the required amount of information is gathered.

Objectives

Assess the efficacy of oral insulin in the prevention or delay of the development of Type 1 diabetes mellitus in subjects with mIAA and other autoantibodies and a proband with Type 1 diabetes.

Outcome Measure

Effect of treatment with oral insulin versus placebo in individuals in the primary stratum ( ICA+ confirmed or GAD65 and ICA512 positive on the same sample with confirmation of at least one of these autoantibodies).

Secondary analyses will be done to assess the effects of oral insulin versus placebo in other categories of subjects defined using different combinations of autoantibodies and metabolic status.

Criteria

Have a proband with T1DM; mIAA confirmed positive within the previous six months; Two samples with at least one autoantibody other than mIAA positive within the previous six months; 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).

Outcome

Among autoantibody-positive relatives of patients with type 1 diabetes, oral insulin at a dose of 7.5mg/d, compared with placebo, did not delay or prevent the development of type 1 diabetes over 2.7 years. These findings do not support oral insulin as used in this study for diabetes prevention.