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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: Parenteral Insulin; Other: Close Observation; Drug: Oral Insulin; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 711
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 45 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborators: 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); National Center for Research Resources (NCRR); Office of Research on Women's Health (ORWH)
• Investigators: Study Chair: Jay S. Skyler, MD, University of Miami

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 1994
• Primary Completion (ACTUAL): June 1, 2003
• Study Completion (ACTUAL): June 1, 2003

Study Registration Dates

• First Submitted: March 13, 2000
• First Submitted That Met QC Criteria: March 13, 2000
• First Posted (ESTIMATE): March 14, 2000

Study Record Updates

• Last Update Posted (ACTUAL): April 24, 2020
• Last Update Submitted That Met QC Criteria: April 22, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: diabetes; prevention; insulin; prediction; C-peptide levels; insulin autoantibodies; pancreatic beta cell autoantibodies; cellular immune responses; prediction of type 1 diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: DPT-1; U01DK061055 (U.S. NIH Grant/Contract); U01DK060782 (NIH); U01DK060916 (NIH); U01DK060987 (NIH); U01DK061010 (NIH); U01DK061029 (NIH); U01DK061030 (NIH); U01DK061034 (NIH); U01DK061035 (NIH); U01DK061036 (NIH); U01DK061037 (NIH); U01DK061038 (NIH); U01DK061040 (NIH); U01DK061041 (NIH); U01DK061042 (NIH); U01DK061058 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data are available at the NIDDK Central Repository: https://repository.niddk.nih.gov/studies/dpt-1/?query=dpt-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No