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

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

This study is currently recruiting participants.
Verified by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), November 2007

Sponsors and Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT00419562

Purpose
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 III

MedlinePlus related topics: Diabetes Diabetes Type 1

ChemIDplus related topics: Insulin

U.S. FDA Resources

Study Type: Interventional
Study Design: Prevention, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study

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

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

Primary Outcome Measures:
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.

Secondary Outcome Measures:
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

Study Start Date: February 2007

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.

Eligibility
Ages Eligible for Study: 3 Years to 45 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

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.
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.
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.
Exclusion Criteria:

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.
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 ? 126 mg/dL (7 mmol/l), OR
2 hour plasma glucose ? 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.
Contacts and Locations

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

Show 36 Study Locations

Sponsors and Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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

Study Chair: Jay Skyler, M.D. University of Miami

Principal Investigator: Jeff Krischer, Ph.D. University of South Florida

More Information

Type 1 Diabetes TrialNet

NIDDK Type 1 Diabetes Clinical Trials

American Diabetes Association

Juvenile Diabetes Foundation International

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.

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. Review. No abstract available.

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.

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.

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.

Lachin JM. Maximum information designs. Clin Trials. 2005;2(5):453-64.

Study ID Numbers: Oral Insulin
First Received: January 4, 2007
Last Updated: November 15, 2007
ClinicalTrials.gov Identifier: NCT00419562
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
"at risk" for developing type 1 diabetes
juvenile diabetes
diabetes mellitus
Type 1 diabetes TrialNet
oral insulin
autoantigen
self tolerance
oral tolerance
DPT-1
prevention
T1D
TrialNet

Study placed in the following topic categories:
Autoimmune Diseases
Metabolic Diseases
Diabetes Mellitus, Type 1
Diabetes Mellitus
Endocrinopathy
Metabolic disorder
Glucose Metabolism Disorders
Insulin

Additional relevant MeSH terms:
Hypoglycemic Agents
Diabetes Mellitus, Type 1
Immune System Diseases
Physiological Effects of Drugs
Endocrine System Diseases
Nutritional and Metabolic Diseases
Diabetes Mellitus
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 11, 2008