Clinical trial NCT00004984: The Diabetes Prevention Trial of Type 1 Diabetes (DPT-1)
Official title: The Diabetes Prevention Trial of Type 1 Diabetes (DPT-1)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 1
Keywords: diabetes
insulin
prediction
prevention
C-peptide levels
insulin autoantibodies
pancreatic beta cell autoantibodies
cellular immune responses
prediction of type 1 diabetes
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor class: NIH
Collaborators: name: National Center for Research Resources (NCRR)
name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Institute on Minority Health and Health Disparities (NIMHD)
name: Office of Research on Women's Health (ORWH)
First posted: 2000-03-14
Enrollment: 711
Sex: ALL
Minimum age (years): 3
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Rate of Type 1 Diabetes Per Year
timeFrame: Glucose tolerance is measured every 6 months for up to 6 years
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Childrens Hospital of Los Angeles, Division of Endocrinology
state: California
city: San Francisco
country: United States
facility: University of California-San Francisco, Milberry Union East RM 405, 500 Parnassus Ave Box 0136
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Denver
country: United States
facility: University of Colorado Barbara Davis Center for Childhood Diabetes
state: Colorado
city: Gainesville
country: United States
facility: University of Florida Diabetes Research Center
state: Florida
city: Miami
country: United States
facility: DPT-1 Operations Coordinating Center
state: Florida
city: Miami
country: United States
facility: University of Miami School of Medicine, Jackson Medical Tower
state: Florida
city: Indianapolis
country: United States
facility: Indiana University, James Whitcomb Riley Hospital for Children, 702 Barnhill Dr, Ste 5960
state: Indiana
city: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: New York
country: United States
facility: Naomi Berrie Diabetes Center, Columbia University, 1150 St. Nicholas Ave
state: New York
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh, Dept/Pediatric Endocrinology, 3705 5th Ave
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas, Children's Medical Center, 6300 Harry Hines Ste 1200
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Research Center, 1201 Ninth Avenue
state: Washington
city: Toronto
country: Canada
facility: Hospital for Sick Children, Division of Endocrinology, 555 University Ave, Rm 5110
state: Ontario
Study officials:
affiliation: University of Miami
name: Jay S. Skyler, MD
role: STUDY_CHAIR
References:
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. doi: 10.1056/NEJM198903023200902.
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. doi: 10.1016/0140-6736(93)91215-8.
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. doi: 10.1073/pnas.88.22.10252.
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 May;28(5):1068-76. doi: 10.2337/diacare.28.5.1068.
citation: 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. doi: 10.1056/NEJMoa012350.
citation: Barker JM, McFann KK, Orban T. Effect of oral insulin on insulin autoantibody levels in the Diabetes Prevention Trial Type 1 oral insulin study. Diabetologia. 2007 Aug;50(8):1603-6. doi: 10.1007/s00125-007-0694-0. Epub 2007 Jun 22.
citation: Johnson SB, Baughcum AE, Hood K, Rafkin-Mervis LE, Schatz DA; DPT-1 Study Group. Participant and parent experiences in the parenteral insulin arm of the diabetes prevention trial for type 1 diabetes. Diabetes Care. 2007 Sep;30(9):2193-8. doi: 10.2337/dc06-2422. Epub 2007 Jun 11.