Diabetes Mellitus, Type 1
Conditions
Keywords
diabetes, insulin, prediction, prevention, C-peptide levels, insulin autoantibodies, pancreatic beta cell autoantibodies, cellular immune responses, prediction of type 1 diabetes
Brief summary
The Diabetes Prevention Trial of Type 1 (DPT-1) was a multicenter randomized, controlled clinical trial designed to determine whether it is possible to delay or prevent the clinical onset of type 1 diabetes through daily doses of insulin in individuals determined to be at risk for the disease. Subjects were recruited from study clinics and through media campaigns.First-degree relatives, 3 to 45 years of age, and second-degree relatives, 3 to 20 years of age, of patients with diabetes were screened for islet-cell antibodies. Those individuals found to be at high risk of diabetes were randomized to receive either close observation or low-dose parenteral insulin. Those individuals found to be at intermediate risk of diabetes are randomized to receive insulin orally or to receive placebo. Patients were followed for up to six years.
Detailed description
The study was divided into three parts: screening, staging, and intervention. Subjects were recruited from study clinics and through media campaigns.First-degree relatives, 3 to 45 years of age, and second-degree relatives, 3 to 20 years of age, of patients with diabetes were screened for islet-cell antibodies. Those with an islet-cell antibody titer of 10 Juvenile Diabetes Foundation (JDF) units or higher were offered staging evaluations. Staging confirmed the presence of islet-cell antibodies, measured insulin antibodies, assessed the first-phase insulin response to intravenous glucose, assessed oral glucose tolerance, and determined the presence or absence of HLA-DQA1\*0102, DQB1\*0602, a protective haplotype, the presence of which excluded subjects from further participation. Islet-cell antibody-positive subjects were then defined as having a high risk of diabetes (a five-year risk of more than 50 percent) and were deemed eligible for the parenteral insulin trial if they had a first-phase insulin response below the threshold (as defined below) on two occasions, if their oral glucose-tolerance results were not completely normal,or both. Relatives who tested positive for islet-cell antibodies and insulin antibodies and who had a first-phase insulin response above the threshold and normal glucose tolerance were defined as having intermediate risk (a five-year risk of 26 to 50 percent) and were deemed eligible for the ongoing oral insulin trial. All randomized subjects were seen every six months, at which time an oral glucose-tolerance test was administered to assess glycemic status, the primary study end point. Mixed-meal tolerance tests were performed at base line, at years 1, 3, and 5, and at the end of the study. Intravenous glucose-tolerance testing was performed at years 2, 4, and 6 and at the end of the study.
Interventions
DRUGParenteral Insulin
Subcutaneous injections of recombinant human ultralente insulin in the morning and in the evening; the initial dose for each injection was 0.125 U per kilogram of body weight.
OTHERClose Observation
Study visits every 6 months including an oral glucose tolerance test
DRUGOral Insulin
Capsules oral insulin, 7.5 mg of recombinant human insulin crystals
DRUGPlacebo
Placebo for oral insulin
Sponsors
National Center for Research Resources (NCRR)
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute on Minority Health and Health Disparities (NIMHD)
Office of Research on Women's Health (ORWH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The oral insulin study was masked, but the parenteral insulin study was not masked
Eligibility
Sex/Gender
ALL
Age
3 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Individuals 3-45 years old who have an immediate family member with type 1 diabetes (such as a child, parent, or sibling) * Individuals 3-20 years old who have an extended family member with type 1 diabetes (such as a cousin, niece, nephew, aunt, uncle, grandparent, or half-sibling)
Exclusion criteria
* To be eligible, a person must: * Not have diabetes already. * Have no previous history of being treated with insulin or oral diabetes medications. * Have not received any prior therapy for prevention of type 1 diabetes such as insulin, nicotinamide, or immunosuppressive drugs (i.e. have not been involved in any previous clinical studies of these agents.) * Have no known serious diseases. * If you are a woman, you must not be planning to become pregnant during the course of the study. You will not be excluded from participation, but are not encouraged to volunteer in the first place if you plan to have a baby during the trial period).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Type 1 Diabetes Per Year | Glucose tolerance is measured every 6 months for up to 6 years | The rate of type 1 diabetes per year is calculated by dividing the number of participants who develop diabetes by the total number of years of follow-up. The diagnosis of diabetes is as defined by the American Diabetes Association (ADA) based on oral glucose testing or the presence of symptoms and unequivocal hyperglycemia. |
Countries
Canada, United States
Outcome results
None listed