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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT00419562
Registration number
NCT00419562
Ethics application status
Date submitted
4/01/2007
Date registered
8/01/2007
Date last updated
7/05/2020
Titles & IDs
Public title
Oral Insulin for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus
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Scientific title
Oral Insulin for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus
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Secondary ID [1]
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UC4DK106993
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Secondary ID [2]
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TN07 Oral Insulin
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Universal Trial Number (UTN)
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Trial acronym
TN07
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Type 1
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Condition category
Condition code
Metabolic and Endocrine
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Diabetes
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Oral Insulin
Treatment: Drugs - Placebo
Experimental: Oral Insulin - 7.5 mg oral insulin capsules given before breakfast on a daily basis.
Placebo Comparator: Placebo - Placebo capsule designed to match appearance of treatment capsule
Treatment: Drugs: Oral Insulin
7.5 mg oral insulin or placebo given before breakfast on a daily basis.
Treatment: Drugs: Placebo
Placebo capsule designed to match active drug
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Rate of Type 1 Diabetes Per Year Among Individuals in the Primary Stratum When Treated With Oral Inulin Versus Placebo
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Assessment method [1]
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Primary outcome is reported as the rate of type 1 diabetes per year among the primary stratum; type 1 diabetes was diagnosed based on metabolic testing and assessment of symptoms. This is calculated by dividing the number of participants who develop diabetes by the total number of years of follow-up.
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Timepoint [1]
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Metabolic and immunological tests were conducted every 6 months; participants were followed for a median of 2.7 years
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Secondary outcome [1]
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Rate of Type 1 Diabetes Per Year in Secondary Stratum (Stratum 2) When Treated With Oral Insulin Versus Placebo
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Assessment method [1]
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Secondary outcome is reported as the rate of type 1 diabetes per year among secondary stratum 2; type 1 diabetes was diagnosed based on metabolic testing and assessment of symptoms. This is calculated by dividing the number of participants who develop diabetes by the total number of years of follow-up.
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Timepoint [1]
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Metabolic and immunological tests were conducted every 6 months; participants were followed for a median of 2.7 years
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Secondary outcome [2]
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Rate of Type 1 Diabetes in Secondary Stratum (Stratum 3+4) When Treated With Oral Insulin Versus Placebo
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Assessment method [2]
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Secondary outcome is reported as the rate of type 1 diabetes per year among secondary stratum 3+4; type 1 diabetes was diagnosed based on metabolic testing and assessment of symptoms. This is calculated by dividing the number of participants who develop diabetes by the total number of years of follow-up.
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Timepoint [2]
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Metabolic and immunological tests were conducted every 6 months; participants were followed for a median of 2.7 years
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Eligibility
Key inclusion criteria
1. Have a proband with Type 1 diabetes mellitus (T1DM). A proband is an individual
diagnosed with diabetes before age 40 and started on insulin therapy within 1-year of
diagnosis. Probands considered to have type 1 diabetes by their physician who do not
meet this definition will be referred to the TrialNet Eligibility Committee.
2. If the proband is a parent, sibling or a child, the study participant must be 3 -45
years of age. If the proband is a second or third degree relative (i.e. niece, nephew,
aunt, uncle, grandparent, cousin, or half-sibling), the study participant must be 3-20
years of age.
3. Willing to sign Informed Consent Form.
4. Oral glucose tolerance test (OGTT) performed within 7 weeks prior to randomization in
which:
- fasting plasma glucose < 110 mg/dL (6.1 mmol/l), and
- 2 hour plasma glucose < 140 mg/dL (7.8 mmol/l)
5. mIAA confirmed positive within the previous six months.
6. Two samples with at least one autoantibody other than mIAA positive within the
previous six months.
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Minimum age
3
Years
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Maximum age
45
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
1. Does not satisfy the above inclusion criteria. Subjects with mIAA positive but no
other autoantibodies positive are not eligible for randomization.
2. Has severe active disease, e.g. chronic active hepatitis, severe cardiac, pulmonary,
renal, hepatic, immune deficiency and/or disease that is likely to limit life
expectancy or lead to therapies such as immunosuppression during the time of the
study.
3. Prior participation in a trial for prevention of T1DM, e.g. nicotinamide, insulin,
immunosuppressive drugs.
4. History of treatment with insulin or oral hypoglycemic agent.
5. History of therapy with immunosuppressive drugs or glucocorticoids within the past two
years for a period of more than three months.
6. Ongoing use of medications known to influence glucose, i.e. sulfonylureas, growth
hormone, metformin, anticonvulsants, thiazide or potassium depleting diuretics, beta
adrenergic blockers, niacin. Subjects on such medications should be changed to a
suitable alternative, if available, and will become eligible one month after
medication is discontinued.
7. Pregnant or intends to become pregnant while on study or lactating.
8. Deemed unlikely or unable to comply with the protocol.
9. OGTT that reveals Diabetes, Impaired Glucose Tolerance (IGT), or Impaired Fasting
Glucose (IFG).
Diabetes is defined by:
- fasting plasma glucose ³ 126 mg/dL (7 mmol/l), OR
- 2 hour plasma glucose ³ 200 mg/dL (11.1 mmol/l)
IGT is defined by:
- fasting plasma glucose < 126 mg/dL (7 mmol/l), and
- 2 hour plasma glucose 140-199 mg/dL (7.8 - 11mmol/l),
IFG is defined by:
- fasting plasma glucose 110-125 mg/dL (6.1-6.9 mmol/l) AND
- 2 hour plasma glucose < 140 mg/dL (7.8 mmol/l)
10. Subject has HLA DQA1*0102, DQB1*0602 haplotype.
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Study design
Purpose of the study
Prevention
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/02/2007
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
1/06/2017
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Sample size
Target
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Accrual to date
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Final
560
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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Walter and Eliza Hall Institute - Parkville
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Recruitment postcode(s) [1]
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3050 - Parkville
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Recruitment outside Australia
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United States of America
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California
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United States of America
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Colorado
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United States of America
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Connecticut
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Florida
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United States of America
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Indiana
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Minnesota
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New York
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Pennsylvania
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United States of America
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Tennessee
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United States of America
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Texas
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United States of America
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Washington
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Canada
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Ontario
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Finland
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Turku
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Italy
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Milan
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United Kingdom
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State/province [15]
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Bristol
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Funding & Sponsors
Primary sponsor type
Government body
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Name
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Address
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Other collaborator category [1]
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Government body
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Name [1]
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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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Other collaborator category [2]
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Government body
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Name [2]
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National Institute of Allergy and Infectious Diseases (NIAID)
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Government body
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Name [3]
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National Center for Research Resources (NCRR)
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Other collaborator category [4]
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Other
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Name [4]
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American Diabetes Association
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Address [4]
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Other collaborator category [5]
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Other
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Name [5]
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Juvenile Diabetes Research Foundation
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Ethics approval
Ethics application status
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Summary
Brief summary
Type 1 diabetes (T1D) is an autoimmune disease. This means that the immune system (the part
of the body which helps fight infections) mistakenly attacks and destroys the cells that
produce insulin (islet cells found in the pancreas). As these cells are destroyed, the body's
ability to produce insulin decreases. There is evidence suggesting that repeated oral
administration of an autoantigen (the same protein that the immune system is reacting to) may
introduce a protective immunity and cause the immune system to stop its attack. An earlier,
large scale study was done to see if oral insulin could delay or prevent the development of
Type 1 diabetes in relatives at risk for developing Type 1 diabetes. The overall results
showed that for the entire study population, oral insulin did not delay or prevent Type 1
diabetes. However, an analysis that was done after the conclusion of the trial suggested a
potential beneficial effect in a subgroup of participants. The participants who seemed to
benefit from oral insulin had higher levels of insulin autoantibodies which are directed
against insulin itself ( called mIAA).
The Type 1 Diabetes TrialNet study group will further explore the potential role of oral
insulin to delay or prevent Type 1 diabetes in a similar group of people. The study will also
include a secondary group of individuals at different levels of risk than those in the
primary cohort to gather information for future studies.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT00419562
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Trial related presentations / publications
Bergerot I, Fabien N, Maguer V, Thivolet C. Oral administration of human insulin to NOD mice generates CD4+ T cells that suppress adoptive transfer of diabetes. J Autoimmun. 1994 Oct;7(5):655-63. doi: 10.1006/jaut.1994.1050.
Muir A, Schatz D, Maclaren N. Antigen-specific immunotherapy: oral tolerance and subcutaneous immunization in the treatment of insulin-dependent diabetes. Diabetes Metab Rev. 1993 Dec;9(4):279-87. doi: 10.1002/dmr.5610090408. No abstract available.
Muir A, Peck A, Clare-Salzler M, Song YH, Cornelius J, Luchetta R, Krischer J, Maclaren N. Insulin immunization of nonobese diabetic mice induces a protective insulitis characterized by diminished intraislet interferon-gamma transcription. J Clin Invest. 1995 Feb;95(2):628-34. doi: 10.1172/JCI117707.
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.
Lachin JM. Maximum information designs. Clin Trials. 2005;2(5):453-64. doi: 10.1191/1740774505cn115oa.
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Public notes
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Contacts
Principal investigator
Name
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Carla J Greenbaum, M.D.
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Address
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Benaroya Research Institute
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT00419562
Download to PDF