Clinical trial NCT02580877: Immune Effects of Oral Insulin in Relatives at Risk for Type 1 Diabetes Mellitus (TN20)
Official title: Exploring Immunologic Effects of Oral Insulin in Relatives at Risk for Type 1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 1 Diabetes
Keywords: oral insulin
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor class: NIH
Collaborators: name: Type 1 Diabetes TrialNet
First posted: 2015-10-20
Enrollment: 92
Sex: ALL
Minimum age (years): 3
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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. .

Eligibility criteria: 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

Primary outcomes:
measure: Change in GAD65 Autoantibody Titer (DK Units/mL)
timeFrame: 13 and 26 weeks after first dose versus baseline
measure: Change in mIAA Autoantibody Titer From Baseline
timeFrame: 13 and 26 weeks after first dose versus baseline
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California - San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: Barbara Davis Center for Childhood Diabetes
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Emory Children's Center
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University-Riley Hospital for Children
state: Indiana
city: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
city: New York
country: United States
facility: Columbia University-Naomi Berrie Diabetes Center
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Seattle
country: United States
facility: Benaroya Research Institute
state: Washington
city: Parkville
country: Australia
facility: Walter and Eliza Hall Institute of Medical Research
state: Victoria
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Milan
country: Italy
facility: San Raffaele Hospital
Study officials:
affiliation: Type 1 Diabetes TrialNet
name: Carla Greenbaum, MD
role: STUDY_CHAIR
References:
citation: 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. doi: 10.2337/diacare.28.5.1068.
citation: Bonifacio E, Ziegler AG, Klingensmith G, Schober E, Bingley PJ, Rottenkolber M, Theil A, Eugster A, Puff R, Peplow C, Buettner F, Lange K, Hasford J, Achenbach P; Pre-POINT Study Group. Effects of high-dose oral insulin on immune responses in children at high risk for type 1 diabetes: the Pre-POINT randomized clinical trial. JAMA. 2015 Apr 21;313(15):1541-9. doi: 10.1001/jama.2015.2928.
citation: Jacobsen LM, Schatz DA. Insulin immunotherapy for pretype 1 diabetes. Curr Opin Endocrinol Diabetes Obes. 2021 Aug 1;28(4):390-396. doi: 10.1097/MED.0000000000000648.