Immune Effects of Oral Insulin in Relatives at Risk for Type 1 Diabetes Mellitus (TN20)

Phase 2

Completed

Interventions: Drug: 67.5 mg oral insulin crystals daily
Drug: 500mg oral insulin crystals every other week

Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Brief Summary: The study is a 2 arm, multi-center, randomized, open-labeled clinical trial designed to assess the effects of varying doses and schedules of oral insulin on immunological and metabolic markers in relatives at risk for type 1 diabetes (T1D).

Detailed Description: A minimum of 40 eligible participants will be identified for study participation from the TrialNet Pathway to Prevention study. Participants must have a relative with type 1 diabetes and be positive for insulin autoantibodies and at least one other autoantibody. All participants will receive active treatment of recombinant insulin treatment in capsules of either 67.5 mg daily or 500mg every other week. Participants will need to visit the study site up to eleven times over one year for blood tests and other study procedures. During the beginning treatment phase there are two visits one month apart for those given the 67.5 mg dose, and three visits two weeks apart to titrate the dose for those in the 500mg treatment group. There are three additional treatment visits at months 2, 3, and 6 and 4 additional visits for follow-up at months 7, 8, 9 and 12. The primary outcome is the change in immune function as assessed by change in level or quality of T lymphocyte or autoantibody biomarkers measured between 13 and 26 weeks compared to baseline. .

Recruitment & Eligibility

Inclusion Criteria

Participants in TrialNet Natural History/Pathway to Prevention Study (TN01); is relative of proband with type 1 diabetes
Between ages 3-45 with normal Oral Glucose Tolerance Test (OGTT) or between ages 3-7 with an abnormal OGTT
Confirmed positive for insulin autoantibodies within previous six months
Confirmed positive for one or more other autoantibodies on two separate occasions within the past six months

Exclusion Criteria

Diagnosed with type 1 diabetes
History of treatment with insulin or oral hypoglycemic agent
History of therapy with immunosuppressive drugs or non-physiologic glucocorticoids within the past two years for a period of more than three months
Ongoing use of medications known to influence glucose tolerance
Pregnant or intending to become pregnant while on study or lactating

Arm && Interventions

Group	Intervention	Description
67.5 mg oral insulin crystals daily	67.5 mg oral insulin crystals daily	67.5 mg oral insulin crystals in capsules (by mouth or sprinkled on food) given daily for six months
500mg oral insulin crystals every other week	500mg oral insulin crystals every other week	500 mg oral insulin crystals in capsules (by mouth or sprinkled on food) given every other week for six months

Primary Outcome Measures

Name	Time	Method
Change in mIAA Autoantibody Titer From Baseline	13 and 26 weeks after first dose versus baseline	Micro-islet autoantibodies (mIAA) autoantibody titers are a measure of of beta cell immune response
Change in GAD65 Autoantibody Titer (DK Units/mL)	13 and 26 weeks after first dose versus baseline	Change in T-lymphocyte (GAD65) biomarker of beta cell specific immune response

Secondary Outcome Measures

Name	Time	Method

Locations (19): Emory Children's Center
🇺🇸
Atlanta, Georgia, United States
University of Pittsburgh
🇺🇸
Pittsburgh, Pennsylvania, United States
University of Chicago
🇺🇸
Chicago, Illinois, United States
University of South Florida
🇺🇸
Tampa, Florida, United States
Columbia University-Naomi Berrie Diabetes Center
🇺🇸
New York, New York, United States
Joslin Diabetes Center
🇺🇸
Boston, Massachusetts, United States
Stanford University
🇺🇸
Stanford, California, United States
University of Florida
🇺🇸
Gainesville, Florida, United States
Baylor College of Medicine
🇺🇸
Houston, Texas, United States
Walter and Eliza Hall Institute of Medical Research
🇦🇺
Parkville, Victoria, Australia
University of Texas Southwestern
🇺🇸
Dallas, Texas, United States
The Hospital for Sick Children
🇨🇦
Toronto, Ontario, Canada
Benaroya Research Institute
🇺🇸
Seattle, Washington, United States
San Raffaele Hospital
🇮🇹
Milan, Italy
University of Miami
🇺🇸
Miami, Florida, United States
Indiana University-Riley Hospital for Children
🇺🇸
Indianapolis, Indiana, United States
University of California - San Francisco
🇺🇸
San Francisco, California, United States
Vanderbilt University
🇺🇸
Nashville, Tennessee, United States
Barbara Davis Center for Childhood Diabetes
🇺🇸
Aurora, Colorado, United States