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

NCT ID: NCT00004984

Last Updated: 2020-04-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

711 participants

Study Classification

INTERVENTIONAL

Study Start Date

1994-02-28

Study Completion Date

2003-06-30

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.

Conditions

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Diabetes Mellitus, Type 1

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
The oral insulin study was masked, but the parenteral insulin study was not masked

Study Groups

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Parenteral Insulin

High risk participants randomized to intervention

Group Type EXPERIMENTAL

Parenteral Insulin

Intervention Type DRUG

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.

Close Observation

High risk participants randomized to observation

Group Type ACTIVE_COMPARATOR

Close Observation

Intervention Type OTHER

Study visits every 6 months including an oral glucose tolerance test

Oral Insulin

Intermediate risk participants randomized to intervention

Group Type EXPERIMENTAL

Oral Insulin

Intervention Type DRUG

Capsules oral insulin, 7.5 mg of recombinant human insulin crystals

Placebo

Intermediate risk participants randomized to placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo for oral insulin

Interventions

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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.

Intervention Type DRUG

Close Observation

Study visits every 6 months including an oral glucose tolerance test

Intervention Type OTHER

Oral Insulin

Capsules oral insulin, 7.5 mg of recombinant human insulin crystals

Intervention Type DRUG

Placebo

Placebo for oral insulin

Intervention Type DRUG

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).
Minimum Eligible Age

3 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Center for Research Resources (NCRR)

NIH

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

National Institute on Minority Health and Health Disparities (NIMHD)

NIH

Sponsor Role collaborator

Office of Research on Women's Health (ORWH)

NIH

Sponsor Role collaborator

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

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jay S. Skyler, MD

Role: STUDY_CHAIR

University of Miami

Locations

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Childrens Hospital of Los Angeles, Division of Endocrinology

Los Angeles, California, United States

Site Status

University of California-San Francisco, Milberry Union East RM 405, 500 Parnassus Ave Box 0136

San Francisco, California, United States

Site Status

Stanford University

Stanford, California, United States

Site Status

University of Colorado Barbara Davis Center for Childhood Diabetes

Denver, Colorado, United States

Site Status

University of Florida Diabetes Research Center

Gainesville, Florida, United States

Site Status

DPT-1 Operations Coordinating Center

Miami, Florida, United States

Site Status

University of Miami School of Medicine, Jackson Medical Tower

Miami, Florida, United States

Site Status

Indiana University, James Whitcomb Riley Hospital for Children, 702 Barnhill Dr, Ste 5960

Indianapolis, Indiana, United States

Site Status

Joslin Diabetes Center

Boston, Massachusetts, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Naomi Berrie Diabetes Center, Columbia University, 1150 St. Nicholas Ave

New York, New York, United States

Site Status

Children's Hospital of Pittsburgh, Dept/Pediatric Endocrinology, 3705 5th Ave

Pittsburgh, Pennsylvania, United States

Site Status

University of Texas, Children's Medical Center, 6300 Harry Hines Ste 1200

Dallas, Texas, United States

Site Status

Virginia Mason Research Center, 1201 Ninth Avenue

Seattle, Washington, United States

Site Status

Hospital for Sick Children, Division of Endocrinology, 555 University Ave, Rm 5110

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type BACKGROUND
PMID: 2644534 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8096268 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1946445 (View on PubMed)

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.

Reference Type RESULT
PMID: 15855569 (View on PubMed)

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.

Reference Type RESULT
PMID: 12037147 (View on PubMed)

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.

Reference Type DERIVED
PMID: 17583798 (View on PubMed)

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.

Reference Type DERIVED
PMID: 17563348 (View on PubMed)

Related Links

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http://www.diabetes.org

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

Other Identifiers

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U01DK060782

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK060916

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK060987

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK061010

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK061029

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK061030

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK061034

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK061035

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK061036

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK061037

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK061038

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK061040

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK061041

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK061042

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK061058

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK061055

Identifier Type: NIH

Identifier Source: secondary_id

View Link

DPT-1

Identifier Type: -

Identifier Source: org_study_id

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