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

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ClinicalTrials.gov Identifier: NCT00419562
Recruitment Status : Active, not recruiting
First Posted : January 8, 2007
Last Update Posted : March 28, 2017
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Drug: Oral Insulin Phase 3

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.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: Oral Insulin for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus
Study Start Date : February 2007
Primary Completion Date : December 2016
Estimated Study Completion Date : June 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: 1
7.5 mg oral insulin capsules given before breakfast on a daily basis.
Drug: Oral Insulin
7.5 mg oral insulin or placebo given before breakfast on a daily basis.
Placebo Comparator: 2
Placebo capsule designed to mimic appearance of treatment capsule
Drug: Oral Insulin
7.5 mg oral insulin or placebo given before breakfast on a daily basis.

Outcome Measures

Primary Outcome Measures :
  1. Effect of treatment with oral insulin versus placebo in individuals in the primary stratum ( ICA+ confirmed or GAD65 and ICA512 positive on the same sample with confirmation of at least one of these autoantibodies). [ Time Frame: Metabolic and immunological tests will be conducted every 6 months ]

Secondary Outcome Measures :
  1. Secondary analyses will be done to assess the effects of oral insulin versus placebo in other categories of subjects defined using different combinations of autoantibodies and metabolic status. [ Time Frame: Metabolic and immunological testing will be conducted every 6 months ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Have a proband with 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. 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.

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.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00419562

United States, California
University of California-San Francisco
San Francisco, California, United States, 94143
Stanford University
Stanford, California, United States, 94305
United States, Colorado
Barbara Davis Center for Childhood Diabetes
Aurora, Colorado, United States, 80010
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06520
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610-0296
University of Miami
Miami, Florida, United States, 33136
United States, Indiana
Indiana University-Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
Columbia University
New York, New York, United States, 10032
United States, Pennsylvania
Childrens Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
Vanderbilt Eskind Diabetes Clinic
Nashville, Tennessee, United States, 37232-8160
United States, Texas
University of Texas
Dallas, Texas, United States, 75235-8858
United States, Washington
Benaroya Research Institute
Seattle, Washington, United States, 98101
Australia, Victoria
Walter and Eliza Hall Institute
Parkville, Victoria, Australia, 3050
Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G1X8
University of Turku
Turku, Finland, FIN-20520
San Raffaele Hospital
Milan, Italy, 20132
United Kingdom
University of Bristol
Bristol, United Kingdom, BS10 5NB
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Allergy and Infectious Diseases (NIAID)
National Center for Research Resources (NCRR)
American Diabetes Association
Juvenile Diabetes Research Foundation
Study Chair: Carla J Greenbaum, M.D. Benaroya Research Institute
Principal Investigator: Jeff Krischer, Ph.D. University of South Florida
More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT00419562     History of Changes
Other Study ID Numbers: Oral Insulin (IND)
First Posted: January 8, 2007    Key Record Dates
Last Update Posted: March 28, 2017
Last Verified: March 2017

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
oral insulin
self tolerance
oral tolerance
"at risk" for developing type 1 diabetes
juvenile diabetes
diabetes mellitus
Type 1 diabetes TrialNet

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin, Globin Zinc
Hypoglycemic Agents
Physiological Effects of Drugs