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

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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00419562
Recruitment Status : Completed
First Posted : January 8, 2007
Results First Posted : February 18, 2020
Last Update Posted : February 18, 2020
Sponsor:
Collaborators:
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
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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 Drug: Placebo 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 560 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
Actual Primary Completion Date : December 2016
Actual Study Completion Date : June 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
Experimental: Oral Insulin
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: Placebo
Placebo capsule designed to match appearance of treatment capsule
Drug: Placebo
Placebo capsule designed to match active drug




Primary Outcome Measures :
  1. 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 ]
    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.


Secondary Outcome Measures :
  1. Rate of Type 1 Diabetes Per Year in Secondary Stratum (Stratum 2) When Treated With Oral Insulin Versus Placebo [ Time Frame: Metabolic and immunological tests were conducted every 6 months; participants were followed for a median of 2.7 years ]
    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.

  2. Rate of Type 1 Diabetes in Secondary Stratum (Stratum 3+4) When Treated With Oral Insulin Versus Placebo [ Time Frame: Metabolic and immunological tests were conducted every 6 months; participants were followed for a median of 2.7 years ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

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.

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.

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


Locations
Show Show 18 study locations
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
Investigators
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Study Chair: Carla J Greenbaum, M.D. Benaroya Research Institute
Principal Investigator: Jeff Krischer, Ph.D. University of South Florida

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT00419562    
Other Study ID Numbers: Oral Insulin (IND)
UC4DK106993 ( U.S. NIH Grant/Contract )
UC4DK117009 ( U.S. NIH Grant/Contract )
First Posted: January 8, 2007    Key Record Dates
Results First Posted: February 18, 2020
Last Update Posted: February 18, 2020
Last Verified: February 2020
Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
oral insulin
oral tolerance
Type 1 diabetes TrialNet
TrialNet
autoantigen
self tolerance
Diabetes Prevention Trial - 1 (DPT-1)
prevention
"at risk" for developing type 1 diabetes
juvenile diabetes
Type 1 diabetes (T1D)
diabetes mellitus
Additional relevant MeSH terms:
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Insulin
Insulin, Globin Zinc
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs