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

Diabetes Mellitus, Type 1 Clinical Trial

— DPT-1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004984
• Other study ID #: DPT-1
• Secondary ID: U01DK060782U01DK
• Status: Completed
• Phase: Phase 3
• Start date: February 1994
• Est. completion date: June 2003

Study information

• Verified date: April 2020
• Source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 711
• Est. completion date: June 2003
• Est. primary completion date: June 2003
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 3 Years to 45 Years

Eligibility

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).

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1

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.

Other:
• Close Observation
Study visits every 6 months including an oral glucose tolerance test

Drug:
• Oral Insulin
Capsules oral insulin, 7.5 mg of recombinant human insulin crystals
• Placebo
Placebo for oral insulin

Locations

Country	Name	City	State
Canada	Hospital for Sick Children, Division of Endocrinology, 555 University Ave, Rm 5110	Toronto	Ontario
United States	Joslin Diabetes Center	Boston	Massachusetts
United States	University of Texas, Children's Medical Center, 6300 Harry Hines Ste 1200	Dallas	Texas
United States	University of Colorado Barbara Davis Center for Childhood Diabetes	Denver	Colorado
United States	University of Florida Diabetes Research Center	Gainesville	Florida
United States	Indiana University, James Whitcomb Riley Hospital for Children, 702 Barnhill Dr, Ste 5960	Indianapolis	Indiana
United States	Childrens Hospital of Los Angeles, Division of Endocrinology	Los Angeles	California
United States	DPT-1 Operations Coordinating Center	Miami	Florida
United States	University of Miami School of Medicine, Jackson Medical Tower	Miami	Florida
United States	University of Minnesota	Minneapolis	Minnesota
United States	Naomi Berrie Diabetes Center, Columbia University, 1150 St. Nicholas Ave	New York	New York
United States	Children's Hospital of Pittsburgh, Dept/Pediatric Endocrinology, 3705 5th Ave	Pittsburgh	Pennsylvania
United States	University of California-San Francisco, Milberry Union East RM 405, 500 Parnassus Ave Box 0136	San Francisco	California
United States	Virginia Mason Research Center, 1201 Ninth Avenue	Seattle	Washington
United States	Stanford University	Stanford	California

Sponsors (6)

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

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (5)

Diabetes Prevention Trial--Type 1 Diabetes Study Group. Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med. 2002 May 30;346(22):1685-91. — View Citation

Keller RJ, Eisenbarth GS, Jackson RA. Insulin prophylaxis in individuals at high risk of type I diabetes. Lancet. 1993 Apr 10;341(8850):927-8. — View Citation

Shah SC, Malone JI, Simpson NE. A randomized trial of intensive insulin therapy in newly diagnosed insulin-dependent diabetes mellitus. N Engl J Med. 1989 Mar 2;320(9):550-4. — View Citation

Skyler JS, Krischer JP, Wolfsdorf J, Cowie C, Palmer JP, Greenbaum C, Cuthbertson D, Rafkin-Mervis LE, Chase HP, Leschek E. Effects of oral insulin in relatives of patients with type 1 diabetes: The Diabetes Prevention Trial--Type 1. Diabetes Care. 2005 M — View Citation

Zhang ZJ, Davidson L, Eisenbarth G, Weiner HL. Suppression of diabetes in nonobese diabetic mice by oral administration of porcine insulin. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10252-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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

External Links

•   Website for the American Diabetes Association which also gives information about the DPT-1.