Diabetes Mellitus, Type 1Phase 3DPT-1NCT00004984
The Diabetes Prevention Trial of Type 1 Diabetes (DPT-1)
A Phase 3 study testing Parenteral Insulin, Close Observation and Oral Insulin in people with Diabetes Mellitus, Type 1, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 15 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 3 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- Parenteral Insulin, Close Observation and Oral Insulin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 711 participants
- Where
- 15 sitesin 2 countries
- Study dates
- Feb 1994to Jun 2003
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 45 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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)
Who cannot join
- 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).
Trial locations and contacts
15 sites in 2 countries.
15 sites in 2 countries
United States14 sites
Joslin Diabetes Center
Boston, Massachusetts, 02215
University of Texas, Children's Medical Center, 6300 Harry Hines Ste 1200
Dallas, Texas, 75235
University of Colorado Barbara Davis Center for Childhood Diabetes
Denver, Colorado, 80262
University of Florida Diabetes Research Center
Gainesville, Florida, 32610-0296
Indiana University, James Whitcomb Riley Hospital for Children, 702 Barnhill Dr, Ste 5960
Indianapolis, Indiana, 46202
Childrens Hospital of Los Angeles, Division of Endocrinology
Los Angeles, California, 90027
DPT-1 Operations Coordinating Center
Miami, Florida, 33136
University of Miami School of Medicine, Jackson Medical Tower
Miami, Florida, 33136
University of Minnesota
Minneapolis, Minnesota, 55455
Naomi Berrie Diabetes Center, Columbia University, 1150 St. Nicholas Ave
New York, New York, 10032
Children's Hospital of Pittsburgh, Dept/Pediatric Endocrinology, 3705 5th Ave
Pittsburgh, Pennsylvania, 15213
University of California-San Francisco, Milberry Union East RM 405, 500 Parnassus Ave Box 0136
San Francisco, California, 94143
Virginia Mason Research Center, 1201 Ninth Avenue
Seattle, Washington, 98101
Stanford University
Stanford, California, 94305-5208
Canada1 site
Hospital for Sick Children, Division of Endocrinology, 555 University Ave, Rm 5110
Toronto, Ontario, M5G-1X8
About this study
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.
Read the 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.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- Parenteral Insulin, Close Observation, Oral Insulin, Placebo
- Keywords
- diabetes, insulin, prediction, prevention, C-peptide levels, insulin autoantibodies, pancreatic beta cell autoantibodies, cellular immune responses, prediction of type 1 diabetes
- Medical subject headings
- Diabetes Mellitus, Type 1, Diabetes Mellitus, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Parenteral InsulinDrug
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 ObservationOther
Study visits every 6 months including an oral glucose tolerance test
Oral InsulinDrug
Capsules oral insulin, 7.5 mg of recombinant human insulin crystals
PlaceboDrug
Placebo for oral insulin
| Study group | Role | What they receive |
|---|---|---|
| Parenteral Insulin | Experimental | High risk participants randomized to intervention Receives: Drug: Parenteral Insulin |
| Close Observation | Active comparator | High risk participants randomized to observation Receives: Other: Close Observation |
| Oral Insulin | Experimental | Intermediate risk participants randomized to intervention Receives: Drug: Oral Insulin |
| Placebo | Placebo comparator | Intermediate risk participants randomized to placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Glucose tolerance is measured every 6 months for up to 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2000 (estimated)
- Study startFeb 1994
- Primary completionJun 2003
- Study completionJun 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 711 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- 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)
- Responsible party
- Sponsor
- Investigators
- Jay S. Skyler, MD, Study chair, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00004984
- Sponsor's protocol ID
- DPT-1
- Other IDs
- U01DK060782, U01DK060916, U01DK060987, U01DK061010, U01DK061029, U01DK061030, U01DK061034, U01DK061035
- Acronym
- DPT-1
- Status last verified
- Apr 2020
- First submitted
- 13 Mar 2000
- Last updated
- 24 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data are available at the NIDDK Central Repository: https://repository.niddk.nih.gov/studies/dpt-1/?query=dpt-1
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.
PubMed 2644534Keller 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.
PubMed 8096268Zhang 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.
PubMed 1946445Skyler 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.
PubMed 15855569Diabetes 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.
PubMed 12037147Barker 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.
PubMed 17583798Johnson 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.
PubMed 17563348
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Diabetes Prevention Trial of Type 1 Diabetes (DPT-1)
- ClinicalTrials.gov ID
- NCT00004984
- Acronym / sponsor ID
- DPT-1 / DPT-1
- Conditions
- Diabetes Mellitus, Type 1
- Keywords
- diabetes, insulin, prediction, prevention, C-peptide levels, insulin autoantibodies, pancreatic beta cell autoantibodies, cellular immune responses
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 711 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Collaborators
- 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)
- Study start
- Feb 1994 (actual)
- Primary completion
- Jun 2003 (actual)
- Study completion
- Jun 2003 (actual)
- First posted
- 14 Mar 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Parenteral Insulin | Experimental | Drug: Parenteral InsulinHigh risk participants randomized to intervention |
| Close Observation | Active comparator | Other: Close ObservationHigh risk participants randomized to observation |
| Oral Insulin | Experimental | Drug: Oral InsulinIntermediate risk participants randomized to intervention |
| Placebo | Placebo comparator | Drug: PlaceboIntermediate risk participants randomized to placebo |
Who may qualify
- Ages
- 3 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- 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)
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Parenteral InsulinSubcutaneous 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. | Drug | Parenteral Insulin |
| Close ObservationStudy visits every 6 months including an oral glucose tolerance test | Other | Close Observation |
| Oral InsulinCapsules oral insulin, 7.5 mg of recombinant human insulin crystals | Drug | Oral Insulin |
| PlaceboPlacebo for oral insulin | Drug | Placebo |
Primary outcome
Rate of Type 1 Diabetes Per Year
Time frame: 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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2020.
- Background: PubMed 2644534Shah 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.
- Background: PubMed 8096268Keller 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.
- Background: PubMed 1946445Zhang 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.
- Results publication: PubMed 15855569Skyler 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.
- Results publication: PubMed 12037147Diabetes 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.
- Derived from this study: PubMed 17583798Barker 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.
- Derived from this study: PubMed 17563348Johnson 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.
- Website for the American Diabetes Association which also gives information about the DPT-1.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Data are available at the NIDDK Central Repository: https://repository.niddk.nih.gov/studies/dpt-1/?query=dpt-1
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jay S. Skyler, MD study chair
University of Miami
15 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Parenteral Insulin, Close Observation and Oral Insulin in people with Diabetes Mellitus, Type 1, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 15 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Type 1 Diabetes Per Year (time frame: Glucose tolerance is measured every 6 months for up to 6 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00004984, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2020.