The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/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
Scientific title
Oral Insulin for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus
Secondary ID [1] 0 0
UC4DK106993
Secondary ID [2] 0 0
TN07 Oral Insulin
Universal Trial Number (UTN)
Trial acronym
TN07
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Type 1 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Rate of Type 1 Diabetes Per Year Among Individuals in the Primary Stratum When Treated With Oral Inulin Versus Placebo - 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.
Timepoint [1] 0 0
Metabolic and immunological tests were conducted every 6 months; participants were followed for a median of 2.7 years
Secondary outcome [1] 0 0
Rate of Type 1 Diabetes Per Year in Secondary Stratum (Stratum 2) When Treated With Oral Insulin Versus Placebo - 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.
Timepoint [1] 0 0
Metabolic and immunological tests were conducted every 6 months; participants were followed for a median of 2.7 years
Secondary outcome [2] 0 0
Rate of Type 1 Diabetes in Secondary Stratum (Stratum 3+4) When Treated With Oral Insulin Versus Placebo - 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.
Timepoint [2] 0 0
Metabolic and immunological tests were conducted every 6 months; participants were followed for a median of 2.7 years

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.
Minimum age
3 Years
Maximum age
45 Years
Gender
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Walter and Eliza Hall Institute - Parkville
Recruitment postcode(s) [1] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
Canada
State/province [12] 0 0
Ontario
Country [13] 0 0
Finland
State/province [13] 0 0
Turku
Country [14] 0 0
Italy
State/province [14] 0 0
Milan
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Bristol

Funding & Sponsors
Primary sponsor type
Government body
Name
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Government body
Name [2] 0 0
National Institute of Allergy and Infectious Diseases (NIAID)
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Government body
Name [3] 0 0
National Center for Research Resources (NCRR)
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
American Diabetes Association
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Juvenile Diabetes Research Foundation
Address [5] 0 0
Country [5] 0 0

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/show/NCT00419562
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.
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. Review.
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.
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.
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.
Lachin JM. Maximum information designs. Clin Trials. 2005;2(5):453-64.
Public notes

Contacts
Principal investigator
Name 0 0
Carla J Greenbaum, M.D.
Address 0 0
Benaroya Research Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications