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

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

Overall Status

Completed

CT.gov ID

NCT00004984

Collaborator

National Center for Research Resources (NCRR) (NIH), National Institute of Allergy and Infectious Diseases (NIAID) (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH), National Institute on Minority Health and Health Disparities (NIMHD) (NIH), Office of Research on Women's Health (ORWH) (NIH)

711

Enrollment

Locations

Arms

111.9

Actual Duration (Months)

47.4

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: Parenteral Insulin Other: Close Observation Drug: Oral Insulin Drug: Placebo	Phase 3

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-DQA10102, DQB10602, 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

711 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

The oral insulin study was masked, but the parenteral insulin study was not masked

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Feb 1, 1994

Actual Primary Completion Date :

Jun 1, 2003

Actual Study Completion Date :

Jun 1, 2003

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 45 Years

Sexes Eligible for Study:

All

Accepts 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Childrens Hospital of Los Angeles, Division of Endocrinology	Los Angeles	California	United States	90027
2	University of California-San Francisco, Milberry Union East RM 405, 500 Parnassus Ave Box 0136	San Francisco	California	United States	94143
3	Stanford University	Stanford	California	United States	94305-5208
4	University of Colorado Barbara Davis Center for Childhood Diabetes	Denver	Colorado	United States	80262
5	University of Florida Diabetes Research Center	Gainesville	Florida	United States	32610-0296
6	DPT-1 Operations Coordinating Center	Miami	Florida	United States	33136
7	University of Miami School of Medicine, Jackson Medical Tower	Miami	Florida	United States	33136
8	Indiana University, James Whitcomb Riley Hospital for Children, 702 Barnhill Dr, Ste 5960	Indianapolis	Indiana	United States	46202
9	Joslin Diabetes Center	Boston	Massachusetts	United States	02215
10	University of Minnesota	Minneapolis	Minnesota	United States	55455
11	Naomi Berrie Diabetes Center, Columbia University, 1150 St. Nicholas Ave	New York	New York	United States	10032
12	Children's Hospital of Pittsburgh, Dept/Pediatric Endocrinology, 3705 5th Ave	Pittsburgh	Pennsylvania	United States	15213
13	University of Texas, Children's Medical Center, 6300 Harry Hines Ste 1200	Dallas	Texas	United States	75235
14	Virginia Mason Research Center, 1201 Ninth Avenue	Seattle	Washington	United States	98101
15	Hospital for Sick Children, Division of Endocrinology, 555 University Ave, Rm 5110	Toronto	Ontario	Canada	M5G-1X8

Sponsors and Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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)