The Diabetes Prevention Trial of Type 1 Diabetes (DPT-1)

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Diabetes Prevention Trial of Type 1 Diabetes (DPT-1)

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: Parenteral Insulin
* Other: Close Observation
* Drug: Oral Insulin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Parenteral Insulin<br>High risk participants randomized to intervention | Drug: Parenteral Insulin<br>* 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.<br>|
| Active Comparator: Close Observation<br>High risk participants randomized to observation | Other: Close Observation<br>* Study visits every 6 months including an oral glucose tolerance test<br>|
| Experimental: Oral Insulin<br>Intermediate risk participants randomized to intervention | Drug: Oral Insulin<br>* Capsules oral insulin, 7.5 mg of recombinant human insulin crystals<br>|
| Placebo Comparator: Placebo<br>Intermediate risk participants randomized to placebo | Drug: Placebo<br>* Placebo for oral insulin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Type 1 Diabetes Per Year | 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. | Glucose tolerance is measured every 6 months for up to 6 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic beta cell autoantibodies, cellular immune responses, prediction of type 1 diabetes, diabetes, insulin, prediction, prevention, C-peptide levels, insulin autoantibodies