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

NCT ID: NCT02580877

Last Updated: 2020-07-27

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

92 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-31

Study Completion Date

2018-03-31

Brief Summary

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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

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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. .

Conditions

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Type 1 Diabetes

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

67.5 mg oral insulin crystals daily

Intervention Type DRUG

human insulin crystals in capsules

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

Group Type EXPERIMENTAL

500mg oral insulin crystals every other week

Intervention Type DRUG

human insulin crystals in capsules

Interventions

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67.5 mg oral insulin crystals daily

human insulin crystals in capsules

Intervention Type DRUG

500mg oral insulin crystals every other week

human insulin crystals in capsules

Intervention Type DRUG

Other Intervention Names

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Humulin R crystals Humulin R crystals

Eligibility Criteria

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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
Minimum Eligible Age

3 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Type 1 Diabetes TrialNet

NETWORK

Sponsor Role collaborator

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

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Carla Greenbaum, MD

Role: STUDY_CHAIR

Type 1 Diabetes TrialNet

Locations

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University of California - San Francisco

San Francisco, California, United States

Site Status

Stanford University

Stanford, California, United States

Site Status

Barbara Davis Center for Childhood Diabetes

Aurora, Colorado, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

University of South Florida

Tampa, Florida, United States

Site Status

Emory Children's Center

Atlanta, Georgia, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Indiana University-Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

Joslin Diabetes Center

Boston, Massachusetts, United States

Site Status

Columbia University-Naomi Berrie Diabetes Center

New York, New York, United States

Site Status

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt University

Nashville, Tennessee, United States

Site Status

University of Texas Southwestern

Dallas, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Benaroya Research Institute

Seattle, Washington, United States

Site Status

Walter and Eliza Hall Institute of Medical Research

Parkville, Victoria, Australia

Site Status

The Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

San Raffaele Hospital

Milan, , Italy

Site Status

Countries

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United States Australia Canada Italy

References

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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.

Reference Type BACKGROUND
PMID: 15855569 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25898052 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34091488 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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UC4DK106993

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UC4DK117009

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Oral Insulin-TN20

Identifier Type: -

Identifier Source: org_study_id

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