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)
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)
ClinicalTrials.gov Identifier:
First received: January 4, 2007
Last updated: December 9, 2013
Last verified: December 2013

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 Intervention Phase
Diabetes Mellitus, Type 1
Drug: Oral Insulin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: Oral Insulin for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus

Resource links provided by NLM:

Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 400
Study Start Date: February 2007
Estimated Study Completion Date: February 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.


Ages Eligible for Study:   3 Years to 45 Years
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00419562

United States, California
University of California-San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: David Ng    415-514-3730    NGDavid@peds.ucsf.edu   
Principal Investigator: Stephen Gitelman, MD         
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Trudy Esrey    650-498-4450    tesrey@stanford.edu   
Principal Investigator: Darrell Wilson, MD         
United States, Colorado
Barbara Davis Center for Childhood Diabetes Recruiting
Aurora, Colorado, United States, 80010
Contact: Hannah Goettle    303-724-6773    hannah.goettle@ucdenver.edu   
Contact: Vicky Gage    1-800-572-3992    victoria.gage@ucdenver.edu   
Principal Investigator: H. Peter Chase, MD         
United States, Connecticut
Yale University Recruiting
New Haven, Connecticut, United States, 06520
Contact: Laurie Feldman    203-737-2760    laurie.feldman@yale.edu   
Principal Investigator: Kevan Herold, MD         
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32610-0296
Contact: Roberta Cook, RN, CDE, BSN    352-334-0857    cookrb@peds.ufl.edu   
Contact: Jessica Ferguson, RN    352-294-0762    jaycee@ufl.edu   
Principal Investigator: Desmond A Schatz, MD         
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Della Matheson, RN,CDE    305-243-3781    dmatheso@med.miami.edu   
Contact: Carlos Blaschke, MD    305-243-3781    cblaschke@med.miami.edu   
Principal Investigator: Jennifer B Marks, MD         
United States, Indiana
Indiana University-Riley Hospital for Children Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Maria Nicholson Spall    866-230-8486    malnicho@iu.edu   
Contact: Bonnie Jagielo    317-944-2551    bjagielo@iu.edu   
Principal Investigator: Linda DiMeglio, MD         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Christine Kwong    612-624-2922    kwong001@umn.edu   
Principal Investigator: Antoinette Moran, MD         
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Ellen Greenberg, MS    212-851-5425    emg25@columbia.edu   
Principal Investigator: Robin S Goland, MD         
United States, Pennsylvania
Childrens Hospital of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Karen Riley    412-692-5210    karen.riley@chp.edu   
Principal Investigator: Dorothy Becker, MD         
United States, Tennessee
Vanderbilt Eskind Diabetes Clinic Recruiting
Nashville, Tennessee, United States, 37232-8160
Contact: Margo Black, RN,BSN,CCRP    615-936-8638    margo.black@vanderbilt.edu   
Principal Investigator: William E Russell, MD         
United States, Texas
University of Texas Recruiting
Dallas, Texas, United States, 75235-8858
Contact: Oralenda Smith    214-648-7123    oralenda.smith@utsouthwestern.edu   
Contact: Lourdes M Pruneda    (214) 648-4717    Maria.Pruneda@utsouthwestern.edu   
Principal Investigator: Philip Raskin, MD         
United States, Washington
Benaroya Research Institute Recruiting
Seattle, Washington, United States, 98101
Contact: Marli McCulloch-Olson    206-515-5233    marli@benaroyaresearch.org   
Contact: Christine Webber    206-515-5237    cwebber@benaroyaresearch.org   
Principal Investigator: Carla Greenbaum, MD         
Australia, Victoria
Walter and Eliza Hall Institute Recruiting
Parkville, Victoria, Australia, 3050
Contact: Felicity Healy    +61-3-9342 7063    felicity.healy@mh.org.au   
Principal Investigator: John Wentworth, MD         
Canada, Ontario
The Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G1X8
Contact: Lesley A Eisel, RN    416-813-7654 ext 1798    lesley.eisel@sickkids.ca   
Principal Investigator: Diane Wherrett, MD         
University of Turku Recruiting
Turku, Finland, FIN-20520
Contact: Tuula Simell, MPH,PhD    +358-2-313 3427    tuula.simell@utu.fl   
Principal Investigator: Olli Simell, M.D.         
San Raffaele Hospital Recruiting
Milan, Italy, 20132
Contact: Pauline Grogan    39-02-2643-7656    grogan.pauline@hsr.it   
Principal Investigator: Emanuele Bosi, MD         
United Kingdom
University of Bristol Recruiting
Bristol, United Kingdom, BS10 5NB
Contact: Claire Matthews, BSc,PhD    +44-117-959-5337    claire.matthews@bristol.ac.uk   
Principal Investigator: Penelope Bingley, MD         
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: Jay Skyler, M.D. University of Miami
Principal Investigator: Jeff Krischer, Ph.D. University of South Florida
  More Information

Additional Information:
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)
Study First Received: January 4, 2007
Last Updated: December 9, 2013
Health Authority: United States: Federal Government

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

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

ClinicalTrials.gov processed this record on November 24, 2015