Oral Insulin for Prevention of Diabetes in Relatives At Risk For Type 1 Diabetes Mellitus (Type 1 Diabetes TrialNet Protocol TN-07)
Subjects eligible for the Oral Insulin Trial will be identified through the TrialNet Natural History Study.
The initial testing for mIAA, and other autoantibodies will be done as part of Natural History screening. Individuals who are mIAA positive may be eligible for more tests as part of Phase 2 or Phase 3 Natural History visit. Those with normal glucose tolerance will be eligible for enrollment into either the Primary or the Secondary Analysis Strata of the Oral Insulin Trial depending on their test results from both the Natural History and Oral Insulin Trial assessments.
An initial study visit, a three month follow-up visit, and then regular visits every six months will occur in the study lasting up to 3 hours each. The hope is that the study will take no longer than 7-8 years from its start in 2007.
Phase 2 Natural History Risk Assessment Visit
MIAA positive individuals will undergo a Phase 2 or 3 Natural History visit consisting of an OGTT, confirmation of autoantibody status, and HLA evaluation. The Oral Insulin Trial will be described to the participant, initiating informed consent for the Oral Insulin Trial. The subject will have up to 7 weeks from the time of the OGTTuntil randomization.
Oral Insulin Initial Visit
Assignment to study group will depend upon antibody and IVGTT results. Any participant either not eligible or not willing to be randomized into the Oral Insulin Trial is eligible for continued follow-up as part of the TrialNet Natural History Study.
The participant will satisfy all of the following:
1. mIAA positive on two separate samples
2. positive for at least one other autoantibody on two samples
3. does not meet the HLA exclusion criteria
4. has normal OGTT
Subjects may be discontinued from treatment due to adverse effects in the judgment of the investigator if related to study medication or subjects who revoke consent to be treated.
This study is designed and will be implemented under the intention-to-treat principle in which all subjects randomized will be included in all analyses. To minimize bias under this principle, this requires adoption of an intent-to-treat design.
A subject whose follow-up lapses during the study will be termed inactive. No subject will be designated as a study dropout. Inactive subjects will not be permanently withdrawn from the study and will be allowed to return to follow-up, and continue with randomized treatment, at any time provided that the subject has not developed diabetes. Those still inactive at the end of the study will be classified as lost to follow-up, and the date so lost will be that at which the subject was last known to be free of diabetes.
1. Have a proband* with T1DM.
2. If the proband is a 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, Grandchild, Cousin), the study participant must be 3-20 years of age.
3. Willing to sign Informed Consent Form.
4. 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.
7. . Non-English speaking subjects will be enrolled in the study by using a fully translated Consent Form and a translator.
* 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.