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Diabetes Mellitus, Type 1Phase 3TN07NCT00419562

Oral Insulin for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus

A Phase 3 study testing Oral Insulin in people with Diabetes Mellitus, Type 1, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 18 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 3 to 45 years
Conditions the study is for
Diabetes Mellitus, Type 1
What is being tested?
Oral Insulin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
560 participants
Where
18 sitesin 6 countries
Study dates
Feb 2007to Jun 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
  • 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.
  • Willing to sign Informed Consent Form.
  • 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)
  • mIAA confirmed positive within the previous six months.
  • Two samples with at least one autoantibody other than mIAA positive within the previous six months.

Who cannot join

  • Does not satisfy the above inclusion criteria. Subjects with mIAA positive but no other autoantibodies positive are not eligible for randomization.
  • 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.
  • Prior participation in a trial for prevention of T1DM, e.g. nicotinamide, insulin, immunosuppressive drugs.
  • History of treatment with insulin or oral hypoglycemic agent.
  • History of therapy with immunosuppressive drugs or glucocorticoids within the past two years for a period of more than three months.
  • 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.
Show all 19Show fewer
  • Pregnant or intends to become pregnant while on study or lactating.
  • Deemed unlikely or unable to comply with the protocol.
  • 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)
  • Subject has HLA DQA1*0102, DQB1*0602 haplotype.

Trial locations and contacts

18 sites in 6 countries.

18 sites in 6 countries

United States13 sites
  • Barbara Davis Center for Childhood Diabetes

    Aurora, Colorado, 80010

  • University of Texas

    Dallas, Texas, 75235-8858

  • University of Florida

    Gainesville, Florida, 32610-0296

  • Indiana University-Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • University of Miami

    Miami, Florida, 33136

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Vanderbilt Eskind Diabetes Clinic

    Nashville, Tennessee, 37232-8160

  • Yale University

    New Haven, Connecticut, 06520

  • Columbia University

    New York, New York, 10032

  • Childrens Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • University of California-San Francisco

    San Francisco, California, 94143

  • Benaroya Research Institute

    Seattle, Washington, 98101

  • Stanford University

    Stanford, California, 94305

Other trials in United States

Australia1 site
  • Walter and Eliza Hall Institute

    Parkville, Victoria, 3050

Other trials in Australia

Canada1 site
  • The Hospital for Sick Children

    Toronto, Ontario, M5G1X8

Other trials in Canada

Finland1 site
  • University of Turku

    Turku, FIN-20520

Other trials in Finland

Italy1 site
  • San Raffaele Hospital

    Milan, 20132

Other trials in Italy

United Kingdom1 site
  • University of Bristol

    Bristol, BS10 5NB

Other trials in United Kingdom

About this study

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.

Read the detailed description

Eligible participants will be randomized to receive either oral insulin (7.5 mg of recombinant human insulin crystals) or placebo daily.

All participants randomized into this study will be seen at a study site for a follow-up evaluation, three and six months after randomization, and every six months thereafter. Participants will be contacted by phone between 6-monthly clinic visits to assess changes in diabetes status, medication compliance and adverse events. These phone contacts will occur approximately 3 months from the date of the participants previous clinic visit.

At the study visits, participants will undergo assessments of their insulin production, immunologic status, and overall health. As the primary outcome measure, subjects will be followed until development of type 1 diabetes or the conclusion of the study. The trial is expected to last approximately 7-8 years or until the required amount of information is gathered.

Being tested
Oral Insulin, Placebo
Keywords
oral insulin, autoantigen, self tolerance, oral tolerance, Diabetes Prevention Trial - 1 (DPT-1), prevention, "at risk" for developing type 1 diabetes, juvenile diabetes, Type 1 diabetes (T1D), diabetes mellitus, Type 1 diabetes TrialNet, TrialNet
Medical subject headings
Diabetes Mellitus, Type 1, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Oral InsulinDrug

    7.5 mg oral insulin or placebo given before breakfast on a daily basis.

  • PlaceboDrug

    Placebo capsule designed to match active drug

Study groups in NCT00419562
Study groupRoleWhat they receive
Oral InsulinExperimental7.5 mg oral insulin capsules given before breakfast on a daily basis.
Receives: Drug: Oral Insulin
PlaceboPlacebo comparatorPlacebo capsule designed to match appearance of treatment capsule
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Metabolic and immunological tests were conducted every 6 months; participants were followed for a median of 2.7 years

Secondary outcomes (2)
  1. 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.

    Measured: Metabolic and immunological tests were conducted every 6 months; participants were followed for a median of 2.7 years

  2. 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.

    Measured: Metabolic and immunological tests were conducted every 6 months; participants were followed for a median of 2.7 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jan 2007 (estimated)
  2. Study startFeb 2007
  3. Primary completionDec 2016
  4. Study completionJun 2017

Resources

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
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
560 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00419562
Sponsor's protocol ID
TN07 Oral Insulin
Other IDs
UC4DK106993, UC4DK117009
Acronym
TN07
Status last verified
Apr 2020
First submitted
4 Jan 2007
Last updated
7 May 2020
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/tn07-oral-insulin/?query=tn07

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.

    PubMed 7840857
  • 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.

    PubMed 7924825
  • 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.

    PubMed 7860747
  • 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.

    PubMed 1946445
  • 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.

    PubMed 15855569
  • Lachin JM. Maximum information designs. Clin Trials. 2005;2(5):453-64. doi: 10.1191/1740774505cn115oa.

    PubMed 16315649
  • Writing Committee for the Type 1 Diabetes TrialNet Oral Insulin Study Group; Krischer JP, Schatz DA, Bundy B, Skyler JS, Greenbaum CJ. Effect of Oral Insulin on Prevention of Diabetes in Relatives of Patients With Type 1 Diabetes: A Randomized Clinical Trial. JAMA. 2017 Nov 21;318(19):1891-1902. doi: 10.1001/jama.2017.17070.

    PubMed 29164254

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Oral Insulin in people with Diabetes Mellitus, Type 1, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 18 sites in 6 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 8 inclusion and 19 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 7 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States, Australia, Canada, Finland, Italy and 1 more country. 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?

Yes. Results are posted in the registry (first posted 18 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 Among Individuals in the Primary Stratum When Treated With Oral Inulin Versus Placebo (time frame: Metabolic and immunological tests were conducted every 6 months; participants were followed for a median of 2.7 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 NCT00419562, 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 7 May 2020.

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