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

Type 1 Diabetes Clinical Trial

Official title:

Exploring Immunologic Effects of Oral Insulin in Relatives at Risk for Type 1

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02580877
• Other study ID #: Oral Insulin-TN20
• Secondary ID: UC4DK106993UC4DK
• Status: Completed
• Phase: Phase 2
• Start date: January 2016
• Est. completion date: March 2018

Study information

• Verified date: July 2020
• Source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: March 2018
• Est. primary completion date: March 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 45 Years

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Drug:
• 67.5 mg oral insulin crystals daily
human insulin crystals in capsules
• 500mg oral insulin crystals every other week
human insulin crystals in capsules

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Type 1 Diabetes TrialNet

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Italy, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

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