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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor:
Collaborators:
American Diabetes Association
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00419562
First received: January 4, 2007
Last updated: December 9, 2013
Last verified: December 2013

January 4, 2007
December 9, 2013
February 2007
February 2014   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
To determine whether oral administration of insulin will prevent or delay the development of Type 1 diabetes in relatives of patients with T1D who are positive for insulin autoantibodies but who do not have a metabolic defect.
Complete list of historical versions of study NCT00419562 on ClinicalTrials.gov Archive Site
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 ] [ Designated as safety issue: No ]
  • To describe the effects of oral insulin in other subjects defined using different combinations of autoantibodies and metabolic status
  • To assess the effects of oral insulin on immunologic and metabolic markers
Not Provided
Not Provided
 
Oral Insulin for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus
Oral Insulin for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Diabetes Mellitus, Type 1
Drug: Oral Insulin
7.5 mg oral insulin or placebo given before breakfast on a daily basis.
  • Experimental: 1
    7.5 mg oral insulin capsules given before breakfast on a daily basis.
    Intervention: Drug: Oral Insulin
  • Placebo Comparator: 2
    Placebo capsule designed to mimic appearance of treatment capsule
    Intervention: Drug: Oral Insulin

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
400
February 2014
February 2014   (final data collection date for primary outcome measure)

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.
Both
3 Years to 45 Years
No
United States,   Australia,   Canada,   Finland,   Italy,   United Kingdom
 
NCT00419562
Oral Insulin (IND)
Yes
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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: Jay Skyler, M.D. University of Miami
Principal Investigator: Jeff Krischer, Ph.D. University of South Florida
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP